SUPPLEMENTARY MATERIAL
Definitions of genetic testing found in
recommendations, guidelines, reports, statements, positions
and other documents from the following organizations:
1. INTERNATIONAL ORGANIZATIONS
WHO - World Health Organization (2012)
Genetic information has the unusual character of being both individual and familial; it can provide
important details about the health status of the patient, but often suggests something about the health
status of blood relatives.
Reference:

Quality and Safety in Genetic testing: An Emerging Concern (WHO 2012):
http://www.who.int/genomics/policy/quality_safety/en/
WHO - World Health Organization (2005)
Genetic testing: DNA analysis to determine the carrier status of an individual; to diagnose a present
disease in the individual; or to determine the individual’s genetic predisposition to developing a particular
condition in the future.
DNA genetic testing involves the analysis of DNA in order to determine the presence of a gene associated
with a particular disease. In general, there are four kinds of genetic tests: Carrier testing determines if the
person tested, who does not himself have the disease, carries a gene for the disease. If two carriers have
a child together, there is a high probability that their offspring will have the disease. Prenatal testing
determines whether a foetus is affected with a genetic abnormality causing a particular condition.
Embryos may also be tested during in vitro fertilization before being surgically implanted into the womb;
this is called pre-implantation diagnosis. For technical reasons, the latter method is not widely practised.
Diagnostic testing determines whether the tested individual in fact has a particular genetic condition or a
genetic predisposition for acquiring the condition later in life. Predictive testing determines the presence
in asymptomatic individuals of an abnormal gene that will lead to a disease in the future, or of a genetic
predisposition for acquiring the condition later in life, in interaction with environmental factors.
Reference:

Genetics, Genomics and the Patenting of DNA Review of Potential Implications for Health in
Developing Countries (WHO 2005): http://www.who.int/genomics/FullReport.pdf
1
WHO - World Health Organization (1998) [1]
5. Genetic Counselling is the provision of accurate, full and unbiased information in a caring, professional
relationship that offers guidance, but allows individuals and families to come to their own decisions.
Counselling is essential before any genetic testing is carried out and should continue afterwards if the
results entail choices for the person and family tested. Genetic Counselling should be available to all, and
should be as non-directive as possible.
Genetic Counselling - Non-directive counselling has two major elements. The first is the provision of
accurate, full and unbiased information that individuals and families may use in making decisions. The
second is an understanding, empathic relationship that offers guidance and helps people to work towards
their own decisions.
…
6. Genetic Screening refers to tests offered to a population group to identify asymptomatic people at an
increased risk from a particular adverse outcome. Examples are phenylalanine screening for
phenylketonuria in newborn babies, as the use of maternal serum biochemical markers in pregnant
women to screen for foetuses with Down syndrome. In all cases, individuals whose screens indicate that
they are at risk must be offered a definitive diagnostic test.
Genetic Testing is the analysis of the status of a particular gene. A genetic test may establish: (a) a
specific diagnosis of a genetic condition in a symptomatic individual; (b) the certainty that a particular
condition will develop in an individual who is asymptomatic at the time of the testing (presymptomatic
diagnosis), or (c) the presence of a genetic predisposition to develop a particular complex disease such as
cancer or cardiovascular disease.
…
8. Presymptomatic testing refers to identification of healthy individuals who may have inherited a gene
for a late onset disease, and if so will develop the disorder if they live long enough (e.g. Huntington
disease).
Susceptibility testing identifies healthy individuals who may have inherited a genetic predisposition that
puts them an increased risk of developing a multifactorial disease, such as heart disease, Alzheimer
disease or cancer but who, even so, may never develop the disease in question.
Presymptomatic testing in the absence of therapeutic options should be available if the following
conditions are met: (a) The information provided by testing will be used to prevent harm to the person
tested, or to spouse, family, prospective children or others. (b) The person is fully informed about the
limitations of testing, including possibilities of uninformative results and inability to predict exact age of
onset or (sometimes) severity of symptoms. (c) The person (or legally authorized representative)is
mentally capable of giving consent. (d) Testing is accompanied by a counselling programme of appropriate
length and intensity for the disorder.
…
10. Prenatal diagnosis of genetic disorders and foetal anomalies has expanded significantly for hundreds
of conditions through DNA analysis of foetal cells and the increased use of ultrasound and maternal serum
biochemical screening (amniocentesis). The purpose of prenatal diagnosis is to rule out the presence in
the foetus of a particular medical condition for which the pregnancy is at an increased risk. This
information is provided to the couple to assist in their decision-making process regarding the available
options, such as carrying the pregnancy to term, preparing for a difficult delivery and for special newborn
care, or terminating the pregnancy. Genetic counselling is particular important prior to prenatal diagnosis
and, after a result indicating an affected foetus, to secure fully informed choices.
Reference:

Proposed International Guidelines on Ethical issues on Medical Genetics and Genetic Services
(WHO 1998): http://www.who.int/genomics/publications/en/ethicalguidelines1998.pdf
2
UNESCO - United Nations Educational, Scientific and Cultural Organization (2003) [2]
Article 2 – Use of terms
For the purposes of this Declaration, the terms used have the following meanings:
(i) Human genetic data: Information about heritable characteristics of individuals obtained by analysis of
nucleic acids or by other scientific analysis;
(ii) Human proteomic data: Information pertaining to an individual’s proteins including their expression,
modification and interaction;
…
(xii) Genetic testing: A procedure to detect the presence or absence of, or change in, a particular gene or
chromosome, including an indirect test for a gene product or other specific metabolite that is primarily
indicative of a specific genetic change;
(xiii) Genetic screening: Large-scale systematic genetic testing offered in a programme to a population or
subsection thereof intended to detect genetic characteristics in asymptomatic people;
(xiv) Genetic counselling: A procedure to explain the possible implications of the findings of genetic
testing or screening, its advantages and risks and where applicable to assist the individual in the long-term
handling of the consequences; It takes place before and after genetic testing and screening;
(xv) Cross-matching: Matching of information about an individual or a group contained in various data
files set up for different purposes.
Reference:

International Declaration on Human Genetic Data, (modified from ACGT and NCB) (2003):
http://portal.unesco.org/en/ev.phpURL_ID=17720&URL_DO=DO_PRINTPAGE&URL_SECTION=201.html
UNESCO - United Nations Educational, Scientific and Cultural Organization (1995)
Genetic counselling provides the link between genetic technologies, several of which have been acquired
through the Human Genome Project, and patient care. It can be defined as a communication process
which involves diagnosis, explanation and options.
Definitions of genetic counselling. The definitions given concur that it is a communication of information
about diagnosed genetic conditions, in a way which allows to make a decision, as autonomous as possible,
and safeguarding the emotional and ethical character of the person who asks for the consultation. While
defined as based on a physician-patient relationship in many countries, the complexity of genetic counselling has led to a new profession of genetic counsellors who are not physicians, especially in NorthAmerica.
• UNITED STATES OF AMERICA: A communication process which involves diagnosis, explanations and
options (as in all medical consultation). In genetic counselling there is a stronger need for detail, especially
in the explanations and options, for which empathetic and emotional support are an essential part.
Counsellors are involved in the ethics of the "people’s right to know".
• UNITED KINGDOM: Counselling entails precision of diagnosis, the estimation of risks, and a supportive
role to ensure that those who are given information are enable to benefit from it and from the
interventions that are available.
• ITALY: The objective, methods and indications of genetic consultation are: Objective: to provide
information to patients (and/or blood relations of a patient) at risk of contracting a disease that may be
hereditary on: consequence of pathology in question; probability of contracting and transmitting it;
possibility of keeping it in check and treating it. Methods: construction and analysis of pedigree;
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calculation of the risk of recurrence (Mendelian or empirical); estimation of the consanguinity coefficient;
more specific analysis; When is counselling indicated: known or presumed illness in patient or family;
congenital malformation; mental retardation; consanguinity; recurrent miscarriage, infertility
• CHILE: A medical process of communication between a physician and a consultant (counselee) where
scientific knowledge, data and facts are exchanged in order to provide a framework to understand the
genetic problem of the patient and the family.
• ARGENTINA: Better called "genetic advising" - a useful tool in preventive medicine.
• ZAIRE: Information on eventual pathology, not therapeutic but predictive.
Reference:

Genetic Counselling (UNESCO 1995):
http://portal.unesco.org/shs/en/file_download.php/e5ec8f48c2de32a26171790bbdda05eccou
nsellingCIB3_en.pdf
CIOMS - Council for International Organizations of Medical Sciences
Documents, but no definitions found.
OECD - Organisation for Economic Co-operation and Development (2007) [3]
1. Scope
This Recommendation applies to quality assurance of molecular genetic testing offered in a clinical
context. It addresses genetic testing for variations in germ line DNA sequences or products arising directly
from changes in heritable genomic sequences that predict effects on the health, or influence the health
management, of an individual.
It focuses on molecular genetic testing for the diagnosis of a particular disease or condition and predictive
genetic testing often carried out before any clinical signs of the disease or condition appear. It is relevant
to tests for heritable DNA variants that predict the response profile of an individual to a drug or course of
therapy and that affect susceptibility to disease, patient prognosis, counselling, treatment and family
planning. It does not address testing carried out only for research purposes.
Reference:

OECD Guidelines for Quality Assurance In Molecular Genetic Testing:
http://www.oecd.org/dataoecd/43/6/38839788.pdf
OECD - Organisation for Economic Co-operation and Development (2000)
Pharmacogenetics refers to the identification of genetic mutations and of polymorphisms involved in or
responsible for variability in drug response, including drug metabolism and disposition and the
development of what is often described as “the right medicine for the right patient”.
The terms “pharmaco-genomics” and “pharmaco-genetics” are often used interchangeably. However,
pharmaco-genomics refers to the application of molecular tools to R&D, including, but not limited to, differential gene expression (DGE), proteomics, tissue immunopathology and histopathology, etc. Pharmaco-genetics refers to the identification of genetic mutations and polymorphism involved in or responsible
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for the variability in drug response including drug metabolism and disposition and the development of
what is often described as “the right medicine for the right patient”.
(What is genetic testing?) There are several possible interpretations and definitions of genetic testing. In
order to delineate the issues to be discussed at the workshop, the OECD steering Group charged with the
organization of the workshop developed the following ad hoc working definition and related explanatory
notes:
Genetic testing is testing for variations in germ line DNA sequences, or for products/effects arising from
changes in heritable sequences, which are predictive of significant health effects.
Genetic counselling provides individuals and families with an inherited disorder with accurate, full and
unbiased information and offers support in the decision-making process (Ad Hoc Committee on genetic
Counselling (1975), “Report to the American Society of Human genetics”, Am. J. Genet. 27, pp 240-242.
T.M. Marteau, B.B. Biesecker (1999), “The future of genetic counselling: An international perspective”,
Nature Genetics, Vol. 22, No 2, pp. 133-137.). It is a complex process, which stands in opposition to eugenic principles and seeks to help families to cope with the diagnosis of an inherited disorder, to face its implications and to make decisions on the basis of their medical and non-medical options. As genetic testing
is involved in the diagnosis of inherited disorders, counselling becomes an integral part of it; it aims at encouraging the autonomy of those involved and reducing the adverse consequences of testing. The need
for counselling derives from: i) the peculiarities of genetic information, as compared to other biomedical
tests, particularly in terms of its predictive and complex character; ii) the gap between the ability to diagnose and to treat an inherited disorder; iii) the social value attributed to heritable characteristics; and iv)
the psycho-social and ethical problems often arising in testing situations. Counselling is traditionally performed by healthcare professionals specifically trained to use procedures different from those in everyday
clinical practice.
References:

OECD, Genetic Testing: Policy Issues for the New Millennium, Organisation for Economic Cooperation and Development (2000):
http://www.oecd.org/document/16/0,2340,en_2649_37407_1895632_1_1_1_37407,00.html

Ronchi E: Genetic Testing – the OECD Agenda, Brussels (2004):
http://ec.europa.eu/research/conferences/2004/genetic/pdf/ronchibrussels.pdf
World Bank
No documents relating to genetic testing were found.
CoE - Council of Europe (CDBI 2008) [4]
ADDITIONAL PROTOCOL
Article 2 – Scope
1 This Protocol applies to tests, which are carried out for health purposes, involving analysis of biological
samples of human origin and aiming specifically to identify the genetic characteristics of a person which
are inherited or acquired during early prenatal development (hereinafter referred to as “genetic tests”).
2 This Protocol does not apply: (a) to genetic tests carried out on the human embryo or foetus; (b) to
genetic tests carried out for research purposes.
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3 For the purposes of paragraph 1: (a) “analysis” refers to: (i) chromosomal analysis, (ii) DNA or RNA
analysis, (iii) analysis of any other element enabling information to be obtained which is equivalent to that
obtained with the methods referred to in sub-paragraphs a.i. and a.ii.; (b) “biological samples” refers to:
(i) biological materials removed for the purpose of the test concerned, (ii) biological materials previously
removed for another purpose.
EXPLANATORY REPORT
INTRODUCTION
12. At its 27th meeting (18–22 October 2004), the CDBI agreed to focus the Protocol on genetic
testing, considering that gene therapy was essentially a research concern and that the value added by the
provisions that could be put in the Protocol remained extremely limited. At the same meeting, the CDBI
agreed to exclude from the scope of the Protocol, genetic testing for identification purposes. A similar
decision was also taken concerning research, already covered in general by the Additional Protocol to the
Convention on Human Rights and Biomedicine, concerning Biomedical Research, adopted by the
Committee of Ministers on 30 June 2004.
13. At its 29th meeting (17–21 October 2005), considering the importance of the ethical
questions raised by prenatal genetic testing, but also their specific and complex nature, the CDBI
confirmed its decision taken in 2001 to exclude genetic testing on the human embryo and foetus from the
scope of the Protocol and considered addressing them independently.
14. The CDBI decided, at its 30th meeting (2–5 May 2006), to split the Protocol and to bring out
separate instruments dealing with genetic testing for health purposes and genetic testing for employment
and insurance purposes.
COMMENTARY ON THE ARTICLES OF THE PROTOCOL
…
Article 2 – Scope
25. This article specifies the scope of the Protocol and defines the main terms it employs.
26. Paragraph 1 states that the Protocol applies to tests, carried out for health purposes, which involve
analysis of biological samples of human origin, and specifically aim to identify genetic characteristics of a
person which are inherited or acquired during early prenatal development.
27. Therefore, not covered by the Protocol are the genetic tests carried out for identification purposes,
such as those carried out within the framework of a medico-legal expertise or in view of establishing
parentage, except if this research is carried out for medical purposes.
28. Furthermore, the requirement that the test involves the analysis of a biological sample excludes as
such the collection of genetic information through family history.
29. The notion of “genetic test” is based here on two elements: the method used and the purpose of the
test. It is to be understood as a procedure including removal of biological material of human origin, where
relevant, as well as the analysis of the personal information obtained there from. This procedure aims
specifically to identify genetic characteristics of a person which are inherited or acquired during early
prenatal development. These genetic characteristics cover those already present in the gametes of the
parents and therefore transmitted by the latter, as well as those which appear during the early stage of
prenatal development before the differentiation of the germ line. It is sometimes referred to the genetic
characteristics inherited or acquired during early prenatal development as “genetic characteristics
transmissible to descendants”. The genetic modifications acquired during lifetime by only certain somatic
cells due for example to external factors in the environment, are therefore not covered.
30. The Protocol covers any genetic test carried out for health purposes on a person whether living or
dead (in the interests of the latter’s family members), or on biological material of human origin. This
6
includes diagnostic, predictive or healthy carrier tests as well as pharmacogenetic tests. Genetic tests
offered in the framework of a genetic screening programme are also covered by the Protocol.
31. The Protocol excludes from its scope genetic tests on the human embryo and foetus. Therefore,
preimplantation (PGD) and prenatal genetic diagnosis (PND) are not covered, including tests on polar
bodies (small haploid cells containing a single set of chromosomes – produced by the ovocyte during
meiosis – the process whereby reproductive cells divide to produce gametes), as well as tests on
components of embryonic or foetal origin (such as DNA or cells) present in the mother’s blood to obtain
information about the foetus or embryo.
32. Genetic tests carried out for research purposes are also excluded from the scope of the Protocol. It
should, however, be noted that Article 12 of the Convention also applies to predictive tests for health research purposes, and states that such tests may only be carried out subject to appropriate genetic
counselling.
33. It has to be noted that some genetic tests, even at an experimental stage, may reveal personal information relevant to the health of the person concerned. The Additional Protocol to the Convention on Human Rights and Biomedicine, concerning biomedical research, provides in Article 13, paragraph 2.v. on information for research participants that these persons must be given specific information on arrangements for access in particular to “information relevant to the participant arising from the research”. Furthermore, the Appendix to that same Protocol provides in paragraph xv that the ethics committee must
be informed of the “arrangements foreseen for information which may be generated and be relevant to
the present or future health of those persons who would participate in research and their family members”. This applies precisely to genetic tests. As the Explanatory Report comments under this provision
(paragraph 57), “… Because proper counselling and other health care assistance may be necessary to explain the nature of the results and the options available to the participant, …”. It is therefore good practice to provide this information and, where appropriate, to offer genetic counselling, according to the
principles set out in Chapter IV of this Protocol.
34. More often than not the analysis of biological samples are analysis of chromosomes, or analysis
concerning DNA or RNA. However, tests using analysis of any other element enabling information to be
obtained which is equivalent to that obtained by the methods referred to above for the determination of
genetic characteristics which are inherited or acquired during early prenatal development are also
considered to be covered by the Protocol.
35. The term “equivalent information” must be understood as referring to information directly linked to
the genetic characteristics sought. The analyses in question enable direct information to be obtained on
the genetic heritage of the person on whom the test is carried out. This is the case in particular with
analysis of gene expression products such as proteins. A distinction must be drawn between analysis
providing information of that kind and analysis simply providing indications on genetic characteristics
without enabling a direct link with them to be established. These indications alone do not provide a
sufficient basis for confirming or otherwise the presence of a genetic modification, but they may call for
further investigations. This distinction may be illustrated, for example, by the case of a genetic
modification leading to hypercholesterolemia in which the gene involved is the MTP (Microsomal
Triglyceride Transfer Protein) gene and its expression product: the MTP protein. The action of this protein
results in a change in the cholesterol level in the blood. However, blood analysis of the cholesterol level
will only give an indication on the genetic characteristics of the person concerned, since the cause of the
hypercholesterolemia may be unconnected with the MTP gene and be due to another factor.
Consequently, this analysis does not provide “information equivalent” to that provided by DNA, RNA or
even the MTP protein, the MTP gene’s expression product. Generally speaking, the definition of the types
of analysis specified in paragraph 3a. does not include analysis of elements that are not directly linked to
the genetic characteristics sought.
36. “Biological sample” refers to biological material removed for the purpose of the genetic test
considered, but also any biological material originally removed for another purpose, on which the test is
performed.
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Reference:

Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Genetic
Testing for Health Purposes: http://conventions.coe.int/Treaty/EN/Reports/Html/203.htm
CoE - Council of Europe (CDBI 2003)
The provisions of this section apply to genetic tests on a living person or materials removed from a living
person performed in order to diagnose a genetic disease or disorder and/or to determine whether the
person possesses one or more genetic traits which may lead that person to develop a disease or a
disorder in the future or may result in a disease or disorder if transmitted to that person’s progeny or
which are relevant to medical treatment. Predictive genetic tests: Tests which are predictive of genetic
diseases or disorders or which serve either to identify a person as a carrier of a gene responsible for a
disease or disorder, or to detect a genetic predisposition or susceptibility to a disease or disorder may be
performed only for health purposes or for scientific research linked to health purposes. Genetic screening
for health purposes: The provisions of this section apply to specific tests offered for health purposes in an
authorised programme, to an entire population or section of a population in order to identify
asymptomatic persons with an increased risk of developing a genetic disease or disorder or transmitting
such a disease or disorder to his or her descendants.
Reference:

Working Party On Human Genetics (CDBI-CO-GT4), Working document on the applications of
genetics for health purposes (2003): http://www.kritischebioethik.de/CDBI-Doc-genetics-forhealth-puposes-2003-03-04.pdf
CoE - Council of Europe (Committee of Ministers 1992) [5]
Purpose, scope and definitions
The purpose of this recommendation is to ensure respect for certain principles in the field of genetic
testing and screening for health care purposes, including medical research.1
For the purposes of this recommendation:
a. the term "genetic tests for health care purposes" refers to tests which serve:
- to diagnose and classify a genetic disease;
- to identify unaffected carriers of a defective gene in order to counsel them about the risk of having
affected children;
- to detect a serious genetic disease before the clinical onset of symptoms in order to improve the quality
of life using secondary preventive measures and/or to avoid giving birth to affected offspring;
- to identify persons at risk of contracting a disease where both a defective gene and a certain lifestyle are
important as causes of the disease;
b. the term "genetic diagnosis" refers to tests carried out to diagnose a presumed ailment on an individual
or several members of a family, in the framework of a family study;
c. the term "genetic screening" refers to genetic tests carried out on a population as a whole or a subset
of it without previous suspicion that the tested individuals may carry the trait.2
1
Genetic testing and screening can be carried out at different levels, such as on chromosomes, genes
(DNA), proteins, organs or a given individual, and can be complemented with aspects of the family history.
2
The essential distinction between genetic diagnosis and genetic screening is that the latter is not
initiated by the individual who is its subject, but by the provider of the screening service.
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Principle 3 - Counselling and support
a. Any genetic testing and screening procedure should be accompanied by appropriate counselling, both
before and after the procedure. Such counselling must be non-directive. The information to be given
should include the pertinent medical facts, the results of tests, as well as the consequences and choices. It
should explain the purpose and the nature of the tests and point out possible risks. It must be adapted to
the circumstances in which individuals and families receive genetic information.
b. Everything should be done to provide, where necessary, continuing support for the tested persons.
Reference:

Recommendation R(92)3 of the Committee of Ministers to Member States on Genetic Testing
and Screening for Health Care Purposes (10 Feb 1992):
https://wcd.coe.int/com.instranet.InstraServlet?command=com.instranet.CmdBlobGet&Instra
netImage=573883&SecMode=1&DocId=601492&Usage=2
2. EUROPEAN (EU27) INSTITUTIONS
EC – European Commission (2005)
Genetic testing and related issues
Genetic testing, its scientific, ethical, legal and social implications, have continued to be subject to debate
both internationally and nationally. New legislation is underway in several EU Member States. Sweden is
expected to adopt a new law in summer 2005, which will address the use of genetic testing in
employment, insurance and health care. The need for a bill has also been addressed by the German
Minister for Health.
For its part, the Commission, in response to the priority action stated in the second progress report on the
Strategy for Europe on Life Sciences and Biotechnology, has established an informal working group
involving officials and experts from Member States to ensure exchange of information and to identify
actions which should be addressed at EU level in order to assure the highest quality of genetic testing. The
need for collaboration and exchange of information at EU level was confirmed at the two meeting
organised so far in May 2004 and March 2005. A survey on national legislations and activities regarding
genetic testing has been prepared. Discussion is continuing on the basis of an “open issues paper”
summarizing the questions that should be tackled by the Commission and Member States.
has started to analyse the directive 98/79/EC on in vitro diagnostic medical devices in the context of
genetic testing and in particular regarding quality and performance assurance of genetic test devices. The
results are expected early 2006;
has implemented, under FP6, a Network of Excellence “EUROGENTEST” (www.eurogentest.org) addressing the issue of harmonisation, validation and standardisation of genetic tests. A public database
including all laboratories in the EU that provide genetic testing (molecular, biochemical, cytogenetics) will
be available early 2006;
is supporting the a series of activities to improve information and to network concerned parties in the
field of rare diseases in the EU Public Health Programme. A number of research projects on genetic
testing of rare diseases are funded under FP5 and FP6. So far the need for a referral system for rare and
complex genetic diseases has been identified as an issue which need special attention
9
An initiative on the protection of worker’s personal data in the employment context is expected to be
launched in 2005. The initiative will also address the processing of genetic data. The European Group on
Ethics issued Opinion (N°18) on the ethics of genetic testing in the work place which has been published
and is available online.
On 17 March 2004, the Article 29 Working Party (National Data Protection Authorities-DPAs) adopted a
working document on the processing of genetic data. One of its main conclusions is that any use of
genetic data for purposes other than directly safeguarding the data subject’s health and pursuing
scientific research should require national rules to be implemented, in accordance with the data
protection principles provided for in Directive 95/46. The processing of genetic data should be authorized
in the employment and insurance fields only in very exceptional cases provided for by law, so as to
protect individuals from being discriminated against on the basis of their genetic profile. The Working
Party may revisit the working document in the light of experience acquired by DPAs and may decide to
focus in detail on specific areas at a later stage, in order to keep in line with the technological
developments linked to the processing of genetic data.
The recommendation from the high level expert group “ETAN-STRATA” [91], addressing the ethical, social
and legal aspects of human genetic testing in research and healthcare applications, has been published in
19 EU languages [92].
Interface between in vitro fertilization techniques and pre-implantation genetic diagnosis (PGD)
JRC-IPTS, together with the European Society of Human Genetics and the European Society for Human
Reproduction and Embryology, organized a workshop in March 2005 on the interface between in vitro
fertilization techniques and pre-implantation genetic diagnosis (PGD), a new application of genetic testing
that is taking off very quickly and with potential large impacts of many kinds. Different regulations,
practices and lack of professional recommendations and guidelines may still lead to large differences
across Member States. There seems to be many questions around the genetic services involved in assisted
reproduction that could benefit from a European coordination effort, including the quality of these
services.
A key issue is the scientific claim that by genetic screening, the routine procedure of implantation of
several embryos per woman can be reduced to implanting a single embryo, with potential large economic
savings (by increasing efficiency) and reduction of multiple births. While not all scientists agree yet with
this claim, the technology is likely to become routine in some clinics. Another key issue is the apparent
generalisation of genetic testing of donors of sperm with very little control since most activities occur in
the private sphere. It seems a fact that a few genetic profiles may be being used massively as donors.
Pre-implantation genetic diagnosis is affected by Directive 2004/23/EC of the European Parliament and of
the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement,
testing, processing, preservation, storage and distribution of human tissues and cells. The donation of
eggs, sperm and embryo fall within its scope and so do the type of genetic screening performed, amount
of clinical history of donors included, amount of genetic information and so forth. The European Society of
Human Genetics (ESHG) and the European Society of Human Reproduction are currently providing input
to a Commission’s guidelines document for implementation of the directive. The background document
being prepared and the discussion at the workshop will tackle these issues.
JRC-IPTS will launch an assessment of the current practices of pre-implantation genetic diagnosis in EU to
define the needs in the area and assess potential options to solve them. Results will be available by mid
2006.
Pharmacogenetics
Pharmacogenetics is the study of inter-individual specific genetic variation related to response to
medicines. It is often said that pharmacogenetics (PG) might enable the pharmaceutical industry to
significantly enhance the productivity of drug discovery and development, allowing also the re-evaluation
of drugs that have failed because of low response rates in the general population. In health care, PG could
10
help reduce the overall cost of disease management, minimizing adverse effects and improving
therapeutic efficacy. As the applications of PG are relatively recent (although the term itself is some 50
years old), a comprehensive picture of the state-of-the-art in the EU in terms of research activities,
commercial applications in drug development, PG-related market and industry structure and probable
future developments has yet to emerge.
JRC-IPTS, together with the European Society of Human Genetics, organized a workshop in 2004 with
experts from different disciplines to review the field. The workshop concluded that the clinical application
of PG has so far been overestimated and expectations have not yet been fulfilled. It has not moved yet to
practical applications, except for very limited drug examples. There is uncertainty when estimating the
possible impacts that a large development of PG applications could have on health care in Europe. There
are multiple ways in which PG will influence health systems and various pressures which will in turn affect
the successful implementation of PG. A paper including a detailed background document and conclusions
of the workshop is under preparation for publication (available in September 2005).
The workshop served to define the scope of an on-going JRC-IPTS study mapping the R&D situation of PG
in Europe, identifying upcoming socio-economic issues and potential barriers to development and
implementation of PG applications in clinical practice. The study includes the detailed cost-benefit
analysis of two case studies of existing PG applications. The final report will be available by July 2005 , and
is expected to be presented in an OECD-organised meeting addressing challenges to health systems from
pharmacogenetics, that will take place in October 2005 in Rome,.
The European Medicines Evaluation Agency (EMEA), currently addressing these issues, organised in
November 2004 an expert meeting to discuss regulatory needs. It was stressed that no legislative
provisions should be made before a wide-ranging consultation process with all relevant stakeholders has
taken place. The importance of ensuring high quality and validation methods for pharmacogenetic tests
was also stressed.
A number of research projects promoting the development of pharmacogenetics in Europe are funded
under FP6, such as the “Genome based therapeutic drugs for depression (GENDEP)”, an integrated project
with 18 partners launched in 2004 and if successful will lead to validated pharmacogenomic methods for
symptom improvement in depression, the prediction of response to psychiatric drug treatment and the
reduction of adverse effects.
Reference:

A Strategy for Europe, Third Progress Report and Future Orientations. Document de travail de
la Commission, Annex to the: Communication from the Commission to the European
Parliament, the Council, the Committee of Regions and the Economic and Social Committee Life sciences and biotechnology, SEC(2005) 850 Brussels (29 Jun 2005): http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:52005SC0850:EN:HTML
EC – European Commission (2005)
3.4.2. Genetic testing
Genetic testing, and its scientific, ethical, legal and social implications, have continued to be debated both
nationally and internationally. Discussions on the need for new legislation or, in some cases, a review of
existing legislation have been initiated across Europe13.
The Commission is conscious of the far-reaching consequences that the lack of an adequate quality
assurance system for genetic testing might have for the person tested and his/her family. Without wishing
in any way to interfere with Member States' competence regarding genetic testing, the Commission
intends, in addition to the priority actions identified in the 2nd progress report, to continue its efforts to
ensure the highest quality of genetic testing in the EU and beyond.
11
Priorities for future actions:
Commission and Member States
► to enhance an EU-wide exchange of information on best practice and cooperation on the development
and use of genetic testing through the open method of coordination. In particular, an evaluation of the
clinical validity/utility of genetic tests and the establishment of a referral system at EU level for genetic
testing of rare and complex diseases will be addressed in 2005- 2006
► to take whatever action appropriate or required, as arising from the coordination
The Commission will
► launch an initiative on the protection of workers' personal data in the employment context, taking
account of the European Group on Ethics in Science and New Technologies Opinion No 18 “Ethical Aspects
of Genetic Testing in the Workplace”. The initiative will also address the processing of genetic data,
► analyse the possibility of setting standards on genetic testing under Article 152 or 153 of the Treaty and
the appropriate legal instrument.
► Analyse the Directive 98/79/EC on in vitro diagnostic medical devices in the context of genetic testing
and in particular regarding quality and performance assurance of genetic test devices.
► Launch a mapping and networking exercise on public health aspects of genetic testing.
3.4.3. Pharmacogenetics
Pharmacogenetics is still in the research and development phase, but its application in drug development
and evaluation is expected, and appropriate measures should be prepared in time for this evolution. The
potential impact of pharmacogenetics on health care and its ethical, legal and socio-economic implications
are still uncertain. The European Medicines Evaluation Agency (EMEA) organised an expert meeting in
November 2004, which stressed that no legislative provisions should be made before a wide-ranging
consultation process with all the relevant stakeholders has taken place, and highlighted the importance of
ensuring high quality and validation methods for pharmacogenetic tests. The research projects funded
under the 6th Framework Programme for Research and the newly established Technology Platform for
Innovative Medicines are expected to give incentives to this field and enhance cooperation between all the
stakeholders concerned.
13 E.g. Austria, Belgium, Czech Republic, Finland, Germany, Netherlands, Slovakia, Spain, Sweden – Add
website link to the survey conducted by DG RTD
Priorities for future actions:
The Commission will
► launch initiatives on the potential benefits, risks and possible new policy issues associated with the
application of pharmacogenetics, including a prospective study, and consider the need for an opinion from
the European Group on Ethics on the ethical implications.
Reference:

Report from the Commission to the European Parliament, the Council, the Committee of the
Regions and the European Economic and Social Committee - Life Sciences and Biotechnology –
A Strategy for Europe Third Progress Report and Future Orientations, COM(2005) 286 final,
Brussels (29 Jun 2005): http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2005:0286:FIN:EN:PDF
12
EC - European Commission (Expert Group on Genetic Testing 2004) [6]
Genetic test: A broad definition was used for genetic testing, i.e. “any test that yields genetic data”. More
specifically a genetic test detects the presence or absence of, or change in, a particular gene or
chromosome, including variants or other inherited polymorphic traits that are not necessarily diagnostic
of disease. They also include biochemical tests for gene products such as enzymes and other proteins.
Genetic data or information relate to inherited or acquired properties that are transmitted during cell
division and that affect subsequent generations of offspring (“germinal genetic data”) or cells and tissues
(“somatic genetic data”). Genetic data comprise: data describing structural properties of DNA (nucleotide
sequence or chemical modifications of nucleotides); or data describing properties of other biological
markers (RNA, proteins, metabolites, other biological constituents) that are the direct consequence of the
underlying DNA template’s structure.
Medical genetic testing: The application of genetic testing to derive information relevant to healthcare:
disease risk, prediction, disease diagnosis, disease prognosis, disease treatment and reproductive choices.
Non-medical genetic testing: The application of genetic testing for all purposes that do not have a
medical aspect, manly for the purpose of identification, e.g. paternity and forensic testing, or the
identification of the presence of animal and plant materials.
Biochemical genetic test: The analysis of human proteins or other molecules predominantly used to
detect gene products showing genetic variations or mutations.
Diagnostic test: A test providing primarily information about an existing condition and its prognosis.
However, it is possible. Although uncommon, that a test applied to diagnose a particular disorder may
provide predictive information about another disorder.
Pharmacogenetics: The study and understanding of the genetic variation between individuals underlying
differential response to drug treatment (efficacy or adverse reactions). The term comes from the words
pharmacology and genetics and describes the interaction of pharmaceuticals and genetics. Like other
forms of genetic testing, the concept of pharmacogenetics encompasses the use of information encoded
in patient’s DNA to help predict their responses to medicines and thereby enhance the effectiveness and
safety of medicines for individual patients. It is important that pharmacogenetics is not confused with
genetic testing for rare monogenetic disease diagnosis or prediction.
References:


The EC Expert Group (Eryl McNally, Anne Cambon-Thomsen, Celia Brazell, Jean-Jacques
Cassiman, Alastair Kent, Klaus Lindpaintner, Paula Lobato de Faria, Detlef Niese, Henriette
Roscam Abbing, Jan Helge Solbakk, Hélène Tack, Erik Tambuyzer, Thomas R. Weihrauch, Erik
Wendel, Barbara Rhode and Maurizio Salvi): 25 Recommendations on the Ethical, Legal and
Social Implications of Genetic Testing. In: Science and Society, The European Commission,
Brussels, ISBN 92-894-7308-8 (2004):
http://ec.europa.eu/research/conferences/2004/genetic/pdf/recommendations_en.pdf
The Independent Expert Group: Ethical, Legal and Social Aspects of Genetic Testing: research,
development and clinical applications. In: Science and Society - Report, The European
Commission, Brussels, ISBN 92-894-7324-X (2004):
http://ec.europa.eu/research/conferences/2004/genetic/pdf/report_en.pdf
EC - European Commission, The European Group on Ethics in Science and New
Technologies, European Commission (EGE) (2003) [7]
DEFINITIONS
For the purposes of this Opinion:
13
(e) “genetic testing” in this context means the use of a scientific test to obtain information on some
aspects of the genetic status of a person, indicative of a present or future medical problem. In the context
of employment, "genetic testing" incorporates "genetic screening" and "genetic monitoring";
(f) “genetic screening” in this context means the use of a scientific test to determine whether a person
possesses particular variant forms of one or more genes in his/her genome;
(g) “genetic monitoring” in this context means the examination, at regular intervals, for chromosomal
abnormalities in samples of cells from a person who may be at risk, in their employment, of exposure to
agents which cause genetic damage;
(h) “personal data” in this context refers to data, however obtained, containing information that might
give an indication of either the present health or predicted future health status of a person.
…
1.1.2. Non-DNA based Genetic Screening
The definition of genetic screening need not be restricted to tests carried out directly on an individual’s
DNA. Many genes are coded instructions for making particular proteins. Others may regulate the timing or
quantity of protein synthesised. Consequently it may be possible in some cases to access indications of
genetic status by measuring the activity of a protein or some of its products. For the purposes of this
Opinion, any test that evaluates specific genes or gene products that may be indicators of a person’s
genetic status are considered to be genetic tests.
1.1.3. Family Medical Histories
Family medical histories can give an indication of possible genetic status with regard to susceptibility to
some diseases and are routinely used by some insurance companies for persons applying for health
insurance. In so far as family medical histories can provide information on a person’s genetic status, which
may have a predictive value for future health as significant as a laboratory performed genetic test, these
are included within our definition of genetic tests.
…
The EGE’s opinion also views the analysis of family history as a genetic test, again insofar as it reveals
characteristics of an individual’s genetic disposition. Some opinions choose to treat it as a different
category. Others choose other solutions. For example, the Greek opinion extends its scope to genetic data
which is ‘any information collected or resulting from genetic tests or analysis of the genetic material of
one or more persons’. The majority of the opinions summarised here do not specify whether the analysis
of family history and gene products are part of their definition of genetic tests. Therefore, in the
summaries that follow, it is specified when an opinion includes family history or gene products in its
definition of genetic testing.
Genetic testing encompasses presymptomatic and susceptibility testing. Whereas presymptomatic tests
identify a mutation in a gene that is guaranteed to cause a disease at one point in the life of person (e.g.
Huntingdon’s disease), susceptibility tests identify mutations that imply a strong risk, but not a certainty,
that a disease will develop. These terms are not explicitly defined in the EGE’s opinion, as the EGE makes
no distinction between these two types in the scope of its recommendations. The WHO-document
however issues recommendations specific to either one of these categories.
Presymptomatic tests are associated with monogenic diseases, and susceptibility tests with polygenic or
multifactorial diseases. In addition to the term polygenic diseases defined in the EGE opinion, some
opinions use the term multifactorial diseases. It designates diseases caused by a combination of genetic
and environmental factors and is often used synonymously with the term polygenic diseases, as they
share the main characteristics.
In addition, the term penetrance is used in some of the existing opinions on the topic. It refers to the
proportion of true false versus true negatives in diagnosis, i.e. the proportion of those who are diagnosed
with a defect gene whose gene is not actually defective versus those who have a detective gene but were
erroneously not diagnosed as such. Penetrance is distinct from predictability, which refers to the
14
likelihood that a person who was correctly diagnosed as having a defective gene will actually develop the
associated disease in the future.
Reference:

Opinion on the Ethical Aspects of Genetic Testing in the Workplace, Opinion n°18 (28 July
2003): http://ec.europa.eu/bepa/european-group-ethics/docs/avis18_compl_en.pdf
EC - European Commission (Group Advisers on the Ethical Implications of
Biotechnology to the EC 1996)
Prenatal screening consists in the extended application of risk assessment procedures to populations of
pregnant women rather than to individuals. Prenatal screening raises additional ethical issues namely in
terms of public health policy.
Preconceptional testing or screening allows individuals to be aware of specific genetic risks to their
offspring. It could involve the development of simple-to-use genetic testing kits, which raise ethical issues
regarding the management of information by the individuals.
Preimplantation diagnosis (PID) consists of analysing the genetic components of very early embryos in
vitro. This allows the transfer of embryos of a particular sex or genotype to the woman’s uterus, thereby
greatly reducing the need to consider termination of pregnancy for couples at risk of transmitting genetic
diseases. PID is currently at the experimental stage of clinical trials. Compared with PND, PID, which
requires in vitro fertilization raises additional ethical question.
Reference:

Ethical Aspects of Prenatal Diagnosis (Opinion of the Group Advisers on the Ethical Implications
of Biotechnology to the European Commission), nº6 (20 Feb 1996):
http://ec.europa.eu/bepa/european-group-ethics/docs/opinion6_en.pdf
European Council
No documents relating to genetic testing were found.
Council of the European Union
No documents relating to genetic testing were found.
European Parliament (2001)
Pharmacogenetics - determining differences in individual reactions to drugs
Pharmacogenomics – development of customised drugs – “personal pills”
Genetic tests - many tests have already been developed to identify or confirm rare genetic diseases.
However, whereas until a few years ago there were only a handful of genetic tests for a small number of
15
hereditary diseases, today, as a result of the impetus provided by academic and commercial laboratories,
there are tests for cystic fibrosis, Huntington’s chorea, muscular dystrophy, and, moreover, a great many
non-hereditary degenerative diseases – the symptoms of which can appear in youth or adulthood – such
as, for example, diabetes, cancer, cardiovascular diseases, high blood pressure, and Alzheimer’s disease.
Genetic tests give incontestable prognoses where some diseases are concerned but in many other cases
reveal no more than a predisposition that can be influenced by external factors such as environment, diet,
and lifestyle. Genetic tests can be carried out for various purposes:
– postnatal diagnostics is used to diagnose a disease, determine the probability that an infant will
develop a given disease, the onset of which does not occur until later in life, and detect genetic alterations
that increase the predisposition to some illnesses such as certain tumours and cardiovascular disorders;
– antenatal diagnostics is used to diagnose a genetic disease or condition in a foetus;
– preimplant diagnostics, an alternative to antenatal diagnosis, is used to diagnose a genetic disease or
condition in an embryo before it is implanted in the uterus (it is an application of in vitro insemination).
Embryonal chromosome analysis using the technique of preimplant genetic diagnosis (PGD) makes it
possible to ensure that embryos will not be implanted if they have abnormal chromosomes and cannot
survive. PGD enables selected, i.e. undeformed, embryos to be implanted and avoids the abortions that
might otherwise follow a conventional antenatal diagnosis at an advanced stage of pregnancy (after the
third month in the case of amniocentesis). It offers an alternative to the normal antenatal diagnosis
methods, especially in cases where parents are at high risk of having a child with severe genetic diseases.
It can be used to detect many single-gene disorders. Data and reports relating to the findings of PGD are
compiled at world level. The PGD Consortium, a body which works in collaboration with the European
Society of Human Reproduction and Embryology (ESHRE), published the most recent findings last
summer. Over 200 babies have been born with the aid of this technique (see papers read by Professors
Devroy and Hovatta at the temporary committee meeting of 27 March 2001). PGD has undoubted
advantages over conventional antenatal diagnostic techniques, in which diagnosis is carried out in about
the third month of gestation, whereas PGD enables an eight-cell embryo to be analysed when it is as little
as three days old. Conventional techniques require samples consisting of many cells, whereas in PGD the
diagnosis can be confined to just a few (from one to three). Furthermore, the findings resulting from
conventional techniques are not known until a couple of weeks after the tests, whereas the findings of
PGD are available within about two days (see paper read by Prof. Devroy at the temporary committee
meeting of 27 March 2001).
Merely from the above description of the technique it is plain to see that PGD entails different ethical implications from conventional diagnostic techniques for a couple who decide to have an abortion in the
light of the diagnosis. PGD methods have prompted disquiet on account of the possibility that people
might want ‘made to measure’ children with particular traits such as intelligence or a gift for music. However, leaving aside the possible objection that ethics has yet to address these questions, it is technically
completely impossible to identify such characteristics in embryos (see paper read by Prof. Hovatta on 27
March 2001).
Gene therapy - Gene therapy is designed to correct anomalous gene function. It is termed somatic gene
therapy when it is used on body cells (blood, organs, etc.) – the main applications are in oncology, cardiovascular medicine, and the treatment of genetic diseases – and the genes inserted will not be passed on
to succeeding generations. It is termed germinal gene therapy when it is practised on reproductive cells
(oocytes and spermatozoa) or embryos. In this case the change will be passed on to offspring.
Genetic medicine - Unlike gene therapy, genetic medicine does not act upon or permanently alter cell
functions. Most of the new medicines are aimed at more easily reachable targets, generally proteins and
enzymes on the surface of a cell or in its cytoplasm. They will be more efficacious but have less potent
side effects and will act on the body in a much more selective way. Doses will be personalised on the basis
of pharmacogenetic tests (papers by Prof. Neri and Mr Goodfellow – meeting of 26 April 2001). Backed by
knowledge of the patient’s predispositions, these medicines will prevent the disease rather than curing
the symptoms.
16
Pharmacogenetics - Pharmacogenetics studies how genetic differences influence the variable reactions of
individual patients to drugs administered to them (papers by Prof. Neri and Mr Goodfellow – meeting of
26 April 2001). The ultimate goal will be to devise a personalised therapy.
Genetic data - Genetic data are regarded as highly specific information. They can reveal important facts
not just about the person examined, but also about the members of his or her family and, in the final
analysis, have a great impact on individual lives and lifestyles, not least as regards decisions to have
children. The legal framework for data protection covers matters such as confidentiality, anonymity,
commercial exploitation, access to information, insurance, employers, and so forth. It might be necessary
to update Directive 95/46/EC on the protection of individuals with regard to the processing of personal
data and on the free movement of such data.
Predictive genetic tests - Tests which are predictive of genetic diseases or which serve either to identify
the subject as a carrier of a gene responsible for a disease or to detect a genetic predisposition or
susceptibility to a disease may be performed only for heath purposes or for scientific research linked to
health purposes, and subject to appropriate genetic counselling.
(Council of Europe Convention on Human Rights and Biomedicine 1997 – similar definition-based on)
Reference:

Report on the ethical, legal, economic and social implications of human genetics, Temporary
Committee on Human genetics and other New technologies in Modern Medicine, European
Parliament (2001): http://europa.eu.int/comm/research/biosociety/pdf/pe_genetics.pdf
JRC-IPTS - Institute for Prospective and Technological Studies, a Joint Research Centre
of the European Commission (2003) [8]
Genetic testing (working definition) is used to identify variations in the DNA sequence that correlate with
a disease or higher risk to develop a disease. This type of test can be used for diagnosis before any
symptoms of disease are recognisable and to determine the personal risk for certain multifactorial
diseases. Thus, the results of genetic testing can have far reaching effects on an individual’s life.
There exist slightly different definitions of “genetic testing”, regarding the comprehensiveness of what is
subsumed under this term. Against the background of reported problems in the field of genetic testing,
the working definition used by OECD is adopted for further discussions: “Genetic testing is testing for
variations in germline DNA sequences, or for products/effects arising from changes in heritable sequences,
which are predictive of significant health effects.” The study targeted only molecular DNA testing for
diagnosis of hereditary diseases, excluding other types of diagnostic tests, such as cytogenetics or
biochemical testing. Pharmacogenetics falls also beyond the scope of the study.
Genetic tests as defined above can be applied serving the following purposes:
Diagnostic testing: This is the most common reason for a request for a genetic test triggered by a patient
presenting clinical signs or symptoms suspected to have a genetic cause. In this case, the test is
performed to confirm, refine or exclude a clinical diagnosis. In many cases the test is widely used as an
exclusion test with a low probability of a positive diagnosis (an example is a test for fragile-X disease on
children with learning difficulty).
Predictive testing: To estimate the risk to a person with no symptoms of developing a genetic disorder in
the future. Usually two forms of predictive testing are distinguished, presymptomatic and predisposition
testing: Presymptomatic testing looks for a mutation (or alteration) in a healthy individual, which, if
present, will almost certainly lead to occurrence of symptoms. This type of testing is most applicable to
adult-onset genetic conditions like Huntington’s chorea. Adults may have no symptoms of disease at the
time of the test but there might be a suspicion of high risk of inheriting a genetic condition from a parent.
17
A minority of individuals in this situation seek predictive information through a genetic test.
Predisposition testing looks for gene mutations that provide a probability of occurrence of the disorder
(e.g. mutations in the genes BRCA 1 and 2 provide certain susceptibility for breast cancer, but a positive
test result does not indicate a 100% risk of developing breast cancer). Many common human diseases –
cardiovascular disease, diabetes, atopy, Alzheimer disease – appear to be multifactorial, i.e. are
susceptible to a number of genetic and environmental influences. The search for the genetic components
of these conditions is currently a major research undertaking, with enormous commercial implications.
Carrier testing: Clarification of presence of a gene mutation for a recessively inherited or X-linked disorder
that will not affect the person but could eventually affect his/her relatives. The test result might be
important for reproductive decisions. Carrier testing in children where the test has no implication for their
own health has been controversial with many geneticists arguing that the possibility of testing should be
delayed until an age when a child can give informed consent for the test.
Prenatal testing: Clarification if the foetus carries certain mutations or alterations responsible for
hereditary diseases. Prenatal testing for Down syndrome and related conditions usually results from
increased risk either because of maternal age or following a pregnancy screen by ultrasonography or a
biochemical test of the mother’s blood. Prenatal diagnosis for single gene disorders is comparatively rare.
It is mainly requested where parents are at high risk and have direct experience of a serious genetic
condition in their own child or in a close relative. A close liaison between obstetric and genetic services is
desirable since parents may choose to end pregnancies shown to be at high risk of a genetic condition
after a test.
Genetic screening: Predictive testing, prenatal testing and carrier testing can also be offered
systematically at the population level. Genetic screening may be concerned with the general population
or with sub-populations defined on the basis of their risk. Population screening programs are usually
decided on and organised by health authorities at the national or regional level. The only well-established
screening programmes are newborn screening programmes: Testing of new-born shortly after birth for
specific disorders such as phenylketonuria, galactosemia, congenital hypothyroidism. Biochemical genetic
testing of newborn infants is recommended for some monogenic conditions and is carried out in specialist
neonatal screening laboratories.
Preimplantation genetic diagnosis (PGD) follows an in vitro fertilisation procedure. Genetic testing is
carried out on one or two cells removed from the early embryo. Embryos shown by the PIGD test not to
have a genetic mutation for the condition examined are then implanted in the uterus to attempt to
establish a pregnancy. The scope and range of testing in the context of this study were circumscribed to
diagnosis of health effects but there are many other common applications of these techniques.
Pharmacogenetics, which refers to the identification of DNA variants (polymorphisms) that are related to
the variability in drug response, is amongst these other applications of genetic testing with a potentially
massive expansion. Adverse drug responses currently account for many hospitalisations and deaths per
year. On average in Europe, up to 7% of hospital patients receiving medication experience severe side
effects and it is thought that pharmacogenetic testing could reduce this incidence and may contribute to
the development of individualised prescription of medicines, or the assurance of the ‘right medicine for
the right patient’.
Another type of DNA-based testing is carried out for disease sub-typing, for example in oncology
laboratories to characterize different types of cancer. The mutations that are under investigation in these
cases are most often so-called somatic changes, which arise in a specific tissue, causing a clone of cells to
proliferate. These techniques are also used in the identity testing for forensic and criminal law
applications, to establish or disprove paternity and to confirm family relationships in immigration
applications. This type of testing is currently widespread and occurs in both the public and private sectors.
Areas of related activity that are economically important and share technologies include genetic testing in
non-human areas to promote animal health and food safety and regulation, for example testing for
permissible levels of genetically modified organisms in food products. Performing a molecular genetic test
18
is a complex process comprising multiple steps: the assignment of the correct indication for sampling,
administrative steps, the sample analysis and the writing of a correct and informative report.
Genetic counselling is a communication and educational process to inform the patient and family
members on benefits and risks of genetic tests, the limitations and meaning of results. It is meant to
inform but also to help the individuals and their families to cope with information gained from testing
(including psychological and social implication). Counselling is extremely important considering the wrong
or exaggerated expectations connected with genetic testing often reported in the media. Genetic tests
are often perceived as being a very accurate method of predicting the future health status of an
individual, but depending on what is being tested the accuracy of predicting the future health status
might vary profoundly.
The role of the counsellor is critical in giving this information to the patient. The quality of genetic testing
cannot be considered isolated from either the type and quality of laboratory reporting, or the quality for
the counselling that the patient receives pre-and post-test.
Genetic testing services include not only the actual technical performance of a genetic test at the lab
bench but also the referral system, the accuracy of test results and their correct reporting, proper
handling of samples and data (in terms of informed consent and privacy) and also pre and post-test
counselling. When discussing quality and harmonization, all these aspects should be taken into
consideration (Nys, H et al, Genetic testing patients’ rights, insurance and employment. A survey of
regulations in the European Union, 2002, European Commission:Brussels p.154).
Reference:

Ibarreta D, Bock AK, Klein C, Rodriguez-Cerezo E (2003): Towards quality assurance and
harmonisation of genetic testing services in the EU, IPTS-JRC and ESTO:
http://ipts.jrc.ec.europa.eu/publications/pub.cfm?id=1124
3. REGULATING AGENCIES
ICH - International Conference on Harmonisation (1997)
Genotoxicity tests can be defined as in vitro and in vivo tests designed to detect compounds which induce
genetic damage directly or indirectly by various mechanisms.
Reference:

Note for Guidance on Genotoxicity: a Standard Batery for Genotoxicity Testing (1997):
http://www.emea.eu.int/pdfs/human/ich/017495en.pdf
ISO - International Organization for Standardization
No documents relating to genetic testing were found.
19
EMA (EMEA) - European Medicines Agency
No documents relating to genetic testing were found.
HGC - Human Genetics Commission, UK (2007) [9]
1.6 In Genes Direct, the HGC defined a genetic test as “a test to detect the presence or absence of, or
change in, a particular gene or chromosome, including an indirect test for a gene product or other specific
metabolite that is primarily indicative of a specific genetic change” and ‘direct’ genetic tests were defined
as those tests “not offered as part of a medical consultation”. A further distinction was made between
direct-to-public and direct-to-consumer tests:
 direct-to-public (DTP) tests are those which are provided via a non-medical intermediary, such as a
pharmacist or alternative health practitioner
 direct-to-consumer (DTC) tests are those where the test is provided without an intermediary between
the consumer and the test provider
1.7 However, within the context of services currently provided in the UK it is often difficult to separate
tests provided directly to the consumer from tests which form part of a medical or health promotion
service provided directly to the consumer via an intermediary. Much of the work carried out by bodies
such as the OECD and EuroGentest (which is discussed in more detail later in this report) is concerned
with genetic tests that are used in medical services but marketed directly to the consumer.
Genes Direct acknowledged this wider issue in identifying the need for some independent mechanism to
consider the scientific and clinical validity and utility of any genetic testing service. If a company wants to
provide a direct genetic test other than through a doctor, it concluded, it should be required to convince a
regulator that the test is suitable. The establishment of the MHRA in the UK therefore seemed to provide
an excellent opportunity to develop an appropriate regulatory framework for direct genetic tests before
they are placed on the market. Furthermore, the UK Genetic Testing Network (UKGTN) has introduced
arrangements for reviewing genetic tests, which also provide a useful basis for the oversight of direct
genetic tests.
3.8 The IVDD Directive, and consequently the MHRA, is only concerned with devices used for medical
purposes. In correspondence, the MHRA has put forward the view that so-called ‘lifestyle’ tests do not,
therefore, fall within their remit. However, this demarcation cannot be relied upon uncritically: if the test
manufacturer makes a medical claim for their product, for example that it indicates increased risk of
cardiovascular disease, then this may fall within the definition of a medical purpose.
Furthermore, it could also be argued that tests which are for the purpose of preventing disease fall within
the scope of the Directive, as the EU Directives define medical devices as those intended “for the purpose
of diagnosis, prevention, monitoring, treatment or alleviation of disease”. They also meet the definition of
an IVDD, i.e. their purpose is “providing information concerning a physiological or pathological state”. It is
noteworthy that the Australian device regulators have recently issued guidance that states that
nutrigenetic tests (regarded as a ‘lifestyle’ test in the UK) will be regulated as IVDDs.
Reference:

More Genes Direct - A report on developments in the availability, marketing and regulation of
genetic tests supplied directly to the public (2007):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/More%20Genes%20Direct%20%20final.pdf
20
HGC - Human Genetics Commission, UK (2006)
Prenatal screening is a public health service that offers pregnant women a test to see if the baby is at an
increased risk of having a particular disorder such as Down’s syndrome.
Prenatal diagnosis is an individual procedure that aims to provide a diagnosis of a particular condition
that the baby might have.
To identify the genetic father of a fetus, a DNA sample from the man (or men) in question is required for
comparison with the fetal sample. Concerns have been raised about “fatherless” paternity testing in this
context. Fatherless testing is when a DNA sample from the supposed father is used without his knowledge
or consent.
PGD was developed in 1990 in the UK. It uses assisted reproductive technology (ART) to create a number
of embryos in the laboratory. These embryos are usually created by fertilising the woman’s egg with her
partner’s sperm, but occasionally donor gametes are used. The fertilised eggs are allowed to develop in
an incubator for 2 to 3 days until they consist of about 8 cells. At this stage, 1 or 2 cells are removed from
the embryo and tested for the specific genetic condition for which the embryo is at increased risk,
enabling the embryos from which they were removed to be identified as affected or unaffected. The
couple can then elect to place in the womb 1 or 2 embryos that are predicted to be unaffected, so
allowing them to embark on a pregnancy that is at very low risk of the condition.
PGD was originally developed for use by couples who know they are at increased risk of having a child
with a genetic disorder but do not wish to consider prenatal diagnosis and the possible subsequent
termination of a pregnancy. Other potential uses are now emerging. These include testing for a predisposition to cancer, late onset and lower penetrance conditions, and the creation of so called ‘saviour
siblings’. These would be selected to have the same tissue type as an existing brother or sister affected
with a disease, and donations of their umbilical cord stem cells or a bone marrow transplant could be
used to treat that sibling.
Reference:

Making Babies: Reproductive decisions and Genetic Technologies (Jan 2006):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/Making%20Babies%20Report%20%20final%20pdf.pdf
HGC - Human Genetics Commission, UK (2004)
Prenatal screening tests can help identify women who are at increased risk of having a baby with a
disorder. Those women identified at increased risk are then offered a diagnostic test.
Diagnostic tests can tell a woman if the baby has a chromosomal abnormality such as Down’s syndrome,
or a genetic disorder like cystic fibrosis.
Prenatal screening is a public health service which offers pregnant women a test to see if the baby is at
significant risk of having a particular disorder such as Down’s syndrome.
Prenatal diagnosis is a type of test which is person and condition specific that aims to provide a diagnosis
of the particular condition the baby might have.
Genetic counsellors are specially trained professionals who generally come from medical or nursing
backgrounds and have first hand knowledge of genetic disorders and their impact.
Prenatal genetic diagnosis (PND) is a type of test which is person and condition specific and aims to
provide a diagnosis of the particular genetic condition the baby might have.
21
Preimplantation genetic diagnosis (PGD) is a technique where embryos created outside the body by IVF
can be tested to see if they have a genetic disorder. One or two cells are removed for testing from the
embryo at the 6-10 cell stage (day 3 of development). Implantation into the woman’s uterus will generally
only be attempted for embryos without the genetic disorder.
PGD is currently being offered for three major categories of disease including: to determine the sex of the
embryo with the aim of avoiding sex-linked disorders such as Duchenne muscular dystrophy; to identify
embryos with single gene disorders such as cystic fibrosis; and to identify embryos with chromosomal
disorders, where a technique called fluorescence in situ hybridisation (FISH) can be used to identify or
confirm abnormal chromosomal rearrangements.
Reference:

Choosing the Future: Genetics and Reproductive Decision Making (Jul 2004):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/ChooseFuturefull.pdf
HGC - Human Genetics Commission, UK (2003) [9]
We have defined direct genetic testing as any test to detect differences in DNA, genes or a chromosome
that is not provided as part of a medical consultation.
Our consultation sought views on the definition of genetic testing. We consulted on whether this term
should be interpreted narrowly (i.e. just to tests on DNA) or more broadly. A broader definition would
include tests that indirectly provided information about genes by detecting or measuring a gene product
(such as a protein or other specific chemical in the body) that is associated with a genetic condition.
We received a number of interesting responses on this point, which we might loosely categorize as:
• Narrow – the definition should be confined to direct information about gene sequences from DNA or
RNA tests or protein analysis that directly relates to gene sequence. Most of these responders felt that
the public were concerned about DNA/gene tests and that oversight should recognise this no matter if it
was somewhat illogical to single such tests out from other health testing services. Some felt that
broadening the definition would make any oversight cumbersome and would inevitably delay matters.
• Broad – the definition should cover all direct and indirect tests that give information about genetic
conditions. The rationale for this seemed to be that indirect testing could be as significant as direct DNA
tests and that by its nature indirect testing may be more prone to variations in analysis or interpretation.
There was also a linked view that limiting oversight to DNA tests would create a loophole that might
encourage the unrestricted proliferation of indirect testing methods.
• Purpose-specific – several responses qualified their comments about a definition by considering the
purpose of a test. Some felt that any oversight should draw a distinction between predicting susceptibility
to complex diseases and predictive testing for monogenic conditions or carrier status. Others felt that the
penetrance of a genetic condition was relevant, others that the use of tests for the diagnosis of serious
conditions or where there could be serious consequences for the consumer if a test was erroneous or the
result misinterpreted, were relevant factors.
We have considered these points and have decided to retain the definition adopted by the ACGT, but
noting the additions that were introduced by the Genetics and Insurance Committee in their criteria for
genetic tests used by insurance companies.
Therefore for the purposes of our report we will define genetic tests as: a test to detect the presence or
absence of, or change in, a particular gene or chromosome, including an indirect test for a gene product
or other specific metabolite that is primarily indicative of a specific genetic change.
22
We conclude that this definition is simple and sufficiently broad to cover the majority of predictive and
diagnostic tests that are likely to be considered as possible direct genetic tests. It also covers other
activities such as DNA paternity testing, but these have not been addressed in our report.
We also note the similar, but more detailed and comprehensive, definition of a genetic test adopted by
the SACGT. It made clear, however, that “tests that are used primarily for other purposes, but that may
contribute to diagnosis of a genetic disease … would not be covered.” In our previous report we also noted
the US Bill on genetic discrimination (as an example of recent US legislation) which defined genetic tests
as “the analysis of human DNA, RNA, chromosomes, proteins and metabolites that detect genotypes,
mutations or chromosomal changes”.
Reference:

Genes Direct: Ensuring the effective oversight of genetic tests supplied directly to the public,
HGC (Mar 2003): http://www.hgc.gov.uk/UploadDocs/DocPub/Document/genesdirect_full.pdf
HGC - Human Genetics Commission, UK (2003) [9]
Genetic test: A test to detect the presence or absence of, or change in, a particular gene or chromosome
(including indirect tests for a product indicative of a specific gene change in a person).
Genetic counselor: In the UK, a non-medical health professional providing genetic counselling in a clinical
setting. Genetic counselling is a communication process between the counsellor and the individual or
family which deals with the medical and other issues associated with the occurrence, or the risk of
occurrence, of a genetic disorder in a family.
Genealogy test: Genetic tests used in the study of family history and descent.
Paternity test: A test which uses DNA analysis to determine whether a man is the biological father of a
particular child.
Pharmacogenetics: The study of how people respond differently to drugs due to their genetic makeup, in
terms of both how well the drug will work and what side effects the person might suffer.
Pharmacogenetics: where people were tested for a likely response to a particular drug before being
given that drug whether as part of a research study or to help with prescribing decisions. While still at an
early stage, the potential use of pharmacogenetics raises a range of social, ethical, legal and economic
issues.
Reference:

Our Genes, Ourselves: Towards appropriate genetic testing – Third Annual Report of the
Human Genetics Commission (2003):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/HGC%203rd%20Annual%20Report,%
20final%20PDF.pdf
HGC - Human Genetics Commission, UK (2000)
Personal Genetic Information: may be defined as any information about the genetic makeup of a person.
This information may be derived from a sequence of the components (the nucleotides, the As, Ts, Cs and
Gs of the genetic code) that make up the DNA molecules in the chromosomes which are found in almost
every cell in our bodies. There is also DNA in the mitochondria (small independently reproducing
organelles found in most cells which power the chemical machinery of the cells). The chromosomes
23
together with the mitochondria and other biochemical structures provide our biological inheritance –our
genome- which is transferred from generation in the egg and sperm.
Genetic Testing in Medical Practice. In the medical context, genetic testing may be undertaken as part of
the process of treating or advising an individual patient. There are four forms of genetic test in this
category:
1) Diagnostic genetic testing – use of genetic testing in individuals with symptoms to aid in his or her
diagnosis, treatment and management.
2) Presymptomatic genetic testing – Primarily carried out in healthy people or those without symptoms
to provide information about that individual’s future health, with respect to specific genetic (also called
inherited or Mendelian) diseases. Such a test result may indicate that the individual has a high likelihood
of developing the disorder or of excluding it. Presymptomatic testing is most frequently used in late onset
dominantly inherited diseases such as Huntington’s disease.
3) Carrier testing – Used to detect individuals who possess a single copy of a gene which follows a
recessive pattern of inheritance (e.g. cystic fibrosis, sickle conditions or thalassaemia). Individuals who are
carriers will not develop the inherited disease but if they have children with another carrier these children
have a one in four chance of developing the disease.
4) Susceptibility tests – gene variants have been discovered which are associated with common
diseases such as Alzheimer’s disease and diabetes. While the associations between carrying the gene
variant and developing the disease do not appear to be close enough to make predictive testing useful, it
is likely that increasingly genetic tests for such variants will be used to target drug treatments to those
most likely to benefit from them. This rapidly growing field of genetically targeted drugs is known as
pharmacogenetics.
Reference:

Whose hands on your genes?, HGC (Nov 2000):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/business_consultations2maintext.pdf
HGC - Human Genetics Commission, UK (2000)
Another key difference in the various regulation is the meaning given to “genetic testing” and “genetic
information”. Some regulation construes “genetic testing” very narrowly, whereas other regulation
defines it more inclusively.
For example, the Swedish Agreement restricts the definition of genetic testing, for the purposes of the
agreement, to presymptomatic, predictive, and susceptibility testing.
In contrast, legislation enacted in South Carolina and Maine provide that a genetic test is any laboratory
test for determining the presence or absence of genetic characteristics in an individual.
Moreover, legislation such as the Medical Checks Act does not define either genetic testing or genetic
information because such definitions are not relevant to the application of its provisions. Accordingly, it is
not really possible, or indeed appropriate, to isolate the definitions of such terms for the purpose of
comparison, as each must be read and understood in its context; that is, in terms of the aims and purpose
of the legislation (or policy), and in light of the terms of other provisions.
Reference:

Protection of Genetic Information: An International Comparison, HGC (Sep 2000):
http://www.hgc.gov.uk/UploadDocs/DocPub/Document/international_regulations.pdf
24
UKGTN - UK Genetic Testing Network (2008) [10]
The definition of a genetic test for the UKGTN continues to be testing for germ line disorders where
Nucleic aAcid is the analyte.
Reference:

First Report of the UKGTN – Supporting Genetic Testing in the NHS, UK Genetic Testing Network
(2008): http://www.ukgtn.nhs.uk/gtn/digitalAssets/0/614_FirstReport.pdf
UKGTN - UK Genetic Testing Network (2005)
The exact definition of a genetic test is still debated but the term genetic test should be regarded as a
shorthand to describe a test to detect (a) a particular genetic variant (or set of variants), (b) for a
particular disease, (c) in a particular population and (d) for a particular purpose. The specification of all
these factors are essential for test evaluation since validity will be to a large extent be determined by
them.
Reference:

Kroese M (2005): Paper for UKGTN Steering Group Meeting - Testing Criteria for Molecular
Genetic Tests (15 Aug 2005):
http://www.ukgtn.nhs.uk/gtn/digitalAssets/0/756_TestingCriteriaPaper.pdf
UKGTN - UK Genetic Testing Network (2003) [10]
The UK Genetic Testing Network (UK GTN) aims to provide high quality and equitable laboratory services
for patients and their families who require genetic advice, diagnosis and management. This document
explains the procedure for introducing or reviewing genetic tests (which are defined as tests for single
gene, germ line disorders where Nucleic Acid is the analyte) to enable them to be considered for adoption
as mainstream NHS services as part of the UK GTN.
Reference:

Procedures and criteria for evaluation of genetic testing for NHS service (Jun 2003):
http://www.genetictestingnetwork.org.uk/gtn/UKGTNinformation/dossier/mainColumnParagraphs/00/document/BACKGROUND%20INFORMATION,
%20GENE%20DOSSIER.pdf
FDA - Food and Drug Administration (2007)
Pharmacogenetic Testing versus Genetic Testing
Fundamentally, testing for pharmacogenetic polymorphisms and genetic mutations is the same and yields
the same general types of results. The target populations and how the test results are used, however, are
expected to be quite different. We consider pharmacogenetic tests for clinical use to be mostly those that
are intended to provide information that may aid in selection of certain therapeutics. When sufficient
clinical information is available, they may also aid in dosage selection of the therapeutic. Therefore, a
pharmacogenetic test target population will typically be composed of candidates for a particular
therapeutic. Target populations of genetic tests, on the other hand, will usually be composed of those
25
who are suspected of having, or are at risk of developing, a particular disease or condition. The following
recommendations will apply to both types of tests unless noted otherwise.
Recommendations for the Preparation of the Pharmacogenetic or Genetic Test Applications
The following are areas that you should address in the preparation of a submission for a medical device
that measures pharmacogenetic or genetic information.
A. Intended Use of a Device
An application for premarket approval or clearance of a device must include a statement of the intended
use of the device. 21 CFR 807.92(a)(5), 814.20(b)(3)(i). The intended use of the device for which approval
or clearance is sought should specify the marker the device is intended to measure, the clinical purpose of
measuring the marker, and the populations to which the device is targeted, where appropriate.
Some devices may have multiple intended uses. We encourage separate applications for each intended
use, if each has unique and separate supporting studies; however, in certain cases of pharmacogenetic
tests, we would consider application of test results in multiple therapeutic settings as a single intended
use. For example, determination of CYP2D6 alleles for the purpose of providing information to aid in drug
selection, without reference to a particular drug, would be an appropriate single intended use, given that
it is well known that CYP2D6 affects the metabolism of many drugs. In other cases, it may be necessary to
identify multiple intended uses. For example, a genetic test for a disease-causing mutation could be used
for testing for carriers, prenatal testing, or for diagnosis. Each of these scenarios would have studies using
different populations. In addition, the different uses might have different risk profiles and, therefore,
might have separate intended use claims and submissions. In these cases, you should provide appropriate
data to support each claimed intended use. You should consult the appropriate review divisions in OIVD
for advice on submitting tests with multiple intended uses.
In this document, "screening" as an intended use is considered to be an indication to test an
asymptomatic individual who is not necessarily at increased risk due to a positive family history. We
recommend that if you are presenting data to support this type of intended use, you carefully consider
the issues listed below.
 Some alleles, genotypes, and mutations will have very low prevalence in given populations. In these
cases, samples from many patients should be obtained in order to detect a significant number of
positives. Furthermore, some alleles, genotypes, or mutations might only be present in particular
ethnic groups, which should therefore participate in the study in significant numbers. Enrichment can
sometimes be appropriate to address these types of problems. However, one of the drawbacks of
enrichment is that sensitivity can be affected by spectrum bias due to irregular retrospective selection
of cases. Also, predictive values are dependent on the prevalence in the intended use population,
which cannot be characterized from a study in which enrichment is used. We recommend that you
contact OIVD for feedback if you are considering using sample enrichment in your studies.
 When many samples are tested for rare events, false positive results could become problematic in that
they may be more common than true positives, due to test error and low prevalence.
 In some cases, properly banked samples may be studied to establish a predictive screening indication
in healthy or asymptomatic individuals. In other cases, a study including long-term follow-up may be
the only way to prove that the test was indeed predictive and to evaluate issues such as penetrance.
In select cases, it may be possible to use postmarket studies to support this type of indication.
Reference:

Guidance for Industry and FDA Staff Pharmacogenetic Tests and Genetic Tests for Heritable
Markers Document (19 Jun 2007):
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDoc
uments/ucm071075.pdf
26
CDC - Centers for Disease Control and Prevention (2005) [11]
Genetic testing
Processes or methods used to analyze human DNA, RNA, genes, chromosomes, proteins, or metabolites in
order to detect mutations, chromosomal changes, karyotypes, phenotypes and/or expression pattern
variation.
Although most genetic testing is used for diagnosing rare genetic disorders, a growing number of genetic
tests have population-based applications, including carrier identification, predictive testing for inherited
risk for common diseases, and pharmacogenetic testing for variation in drug response. These tests and
other anticipated applications of genomic technologies for use in screening and prevention have the
potential for broad public health impact.
Reference:

Genomics and Population Health, CDC (2005):
http://www.cdc.gov/genomics/about/file/print/2005report/fullReport.pdf
CDC - Centers for Disease Control and Prevention (2005)
Analyte - The substance measured by a laboratory test; for instance, a specific mutation or allele.
Carrier - An individual who possesses a mutant allele but does not express it in the phenotype, either
because of a dominant allelic partner or because the mutation is nonpenetrant.
Cytogenetics - The study of the physical appearance of chromosomes.
Diagnostic test - A test performed to determine the presence or absence of a specific medical condition.
Gene - A hereditary unit that occupies a certain position on a chromosome; a unit that has one or more
specific effects on the phenotype, and can mutate to various allelic forms. The fundamental physical and
functional unit of heredity. A gene is an ordered sequence of nucleotides located in a particular position
on a particular chromosome that encodes a specific functional product (i.e., a protein or RNA molecule).
Gene product - The biochemical material, either RNA or protein, resulting from expression of a gene. The
amount of gene product is used to measure how active a gene is; abnormal amounts can be correlated
with disease-causing alleles.
Genetic counseling - The educational process that helps individuals, couples, or families to understand
genetic information and issues that may have an impact on them.
Genetic polymorphism - Difference in DNA sequence among individuals, groups, or populations (e.g.,
genes for blue eyes versus brown eyes).
Genetic predisposition - A genotype that increases the risk but is insufficient to result in disease. Impaired
expression of alleles at other gene loci and/or environmental factors are needed before disease appears.
Genetic screening - Testing a group of people to identify individuals at high risk of having or passing on a
specific genetic disorder.
Genetic testing - Analyzing an individual's genetic material to determine predisposition to a particular
health condition or to confirm a diagnosis of genetic disease.
Mutation - Any heritable change in DNA sequence. A process by which genes undergo a structural change.
Polymorphism - Frequently occurring (common), usually normal variation, in a defined nucleotide
sequence. Polymorphisms in genes may result in protein polymorphisms. A protein polymorphism is said
to occur when the most common allele has a frequency of no greater than 99%.
27
Screening test – A test designed to identify subjects who are at sufficient risk of a specific disorder to
benefit from further investigation or preventive action, among those who have not sought medical
attention on account of symptoms of that disorder.
Reference:

Draft Genetic Test Review - Cystic Fibrosis Glossary:
http://www.cdc.gov/genomics/gtesting/file/print/FBR/CFGlossary.pdf
CLIAC - Clinical Laboratory Improvement Advisory Committee (Genetic Testing
Subcommittee 1998)
Genetic Test Definition
The Workgroup reviewed the two working definitions for genetic testing proposed by the CLIAC. Several
members stressed the importance of developing definitions that are concise and specific, yet flexible
enough to accommodate the future. After a brief discussion of whether it is necessary to identify that
“individuals, families or populations” are the subject of genetic tests in both definitions, the Workgroup
decided that it is not needed. Other minor revisions were proposed, and the working definitions that
resulted from the Workgroup discussion are as follows:
Molecular genetic and cytogenetic tests - The analysis of human DNA, RNA, and chromosomes, in order
to detect heritable or acquired disease-related genotypes, mutations, phenotypes, or karyotypes for
clinical purposes. Such purposes include predicting risk of disease, identifying carriers, and establishing
prenatal or clinical diagnoses or prognoses.
Biochemical genetic test - The analysis of materials derived from the human body, including human
proteins, and certain metabolites predominantly used to detect inborn errors of metabolism, heritable
genotypes, or mutations for clinical purposes. Such purposes include predicting risk of disease, identifying
carriers, and establishing prenatal or clinical diagnoses or prognoses. [Tests that are used primarily for
other purposes, but may contribute to diagnosing a genetic disease (e.g. blood smear, certain serum
chemistries), would not be covered by this definition].
Reference:

Summary Report, US Department of Health & Human Services, Public Health Service, CDC (3031 Jul 1998): http://wwwn.cdc.gov/cliac/pdf/gsc0798.pdf
AHRQ - Agency for Healthcare Research and Quality, US Department of Health and
Human Services (2010) [12]
In this report, we use the term “molecular test” (MT) interchangeably with the term “molecular genetic
test”. We adopted the definition of molecular genetic test recommended by the Genetic Work Group of
the Clinical Laboratory Improvement Advisory Committee. The Work Group defined a genetic molecular
test as “an analysis performed on human DNA or RNA to detect heritable or acquired disease-related
genotypes, mutations, or phenotypes for clinical purposes” 1
According to this definition, cytogenetic tests, which are performed on human chromosomes, and
biochemical genetic tests, which analyze human proteins and certain metabolites, are beyond the scope
of this report. However, molecular cytogenetic tests (e.g., the tests using the fluorescence in situ
hybridization (FISH) technology) in which analyses cross both the chromosome and the DNA levels are
included in this report. In this report, we also consider a test performed on pathogen (e.g., bacterial, viral
28
or fungal) DNA or RNA as a molecular test if the purpose of the test is to diagnose an infectious disease
caused by the pathogen in human.
In accordance with the objectives outlined in the scope of work, this horizon scan only includes molecular
tests of potential clinical relevance to the Medicare over-65-year-old population as of October 31, 2008.
Particularly, molecular tests for the following purposes are addressed: tests used for diagnostic purposes
in symptomatic individuals, tests used as prognostic indicators, tests used to monitor response to therapy,
and tests used to choose therapies for a known disease entity or used to adjust medication dosing.
Excluded from this report are molecular tests used primarily for blood supply screening, tissue typing,
epidemiological surveillance, pure research, and forensic purposes. Tests used to screen for inherited
diseases of metabolism or other conditions of greater relevance to the pediatric population (e.g., the
diagnostic or screening tests for cystic fibrosis) are also beyond the scope of this report.
A molecular test can be performed using either a protocol developed within the laboratory or a test kit
developed by a manufacturer for commercial distribution to multiple laboratories. Commercially
distributed test kits include all reagents and instructions needed to complete the test procedure and
interpret the results. These commercial kits are currently regulated by the FDA as in-vitro diagnostic
devices. Laboratory-developed molecular tests (LDMTs), also known as homebrew or in-house molecular
tests, are developed within laboratories using either FDA regulated or self-developed analyte specific
reagents (ASRs) and intended for use solely in the test developer‘s laboratory. LDMTs are not actively
regulated by the FDA, although the Agency claims its jurisdiction over such tests. This report focuses on
LDMTs; however, in cases where we cannot tell whether a test offered by a laboratory uses a commercial
kit or is one developed in house, we included the test and labeled it differently from those clearly
identified as LDMTs.
Reference:


Quality, Regulation and Clinical Utility of Laboratory-developed Molecular Tests, Technology
Assessment Report by the ECRI Institute Evidence-based Practice Center (6 Oct 2010):
http://camec.glp.net/c/document_library/get_file?p_l_id=844091&folderId=754745&name=D
LFE-21304pdf
1
Tabar P (2005) The urge to converge. A network primed for data and high-quality voice over IP can accomplish plenty.
Healthc Inform 22: 35-6, 38, 40
4. Genetics Scientific and Professionals Organizations
IFHGS - International Federation of Human Genetics Societies
Documents, but no definitions found.
ESHG - European Society of Human Genetics and ESHRE - European Society of Human
Reproduction and Embryology (PPPC 2006)
Prenatal diagnosis (PND) is a diagnostic or pre-symptomatic test carried out on a developing foetus
through amniocentesis, chorionic villus sampling, foetal blood sampling, collecting foetal material in
maternal circulation, or ultrasound. PND is used to detect a foetus with chromosomal aberration,
congenital malformation or disease, or that is at risk for disease and thus offers the parents the opinion to
29
terminate the pregnancy in order to prevent the birth of offspring with genetic and/or congenital
anomalies. Couples who have not experienced prenatal testing before, the patients with current
infertility, or moral/religious objections, in general opt for prenatal diagnosis (De Die-Smulders et al.,
2005)
Preimplantation genetic diagnosis (PGD) was introduced at the beginning of the 1990s as an alternative
to prenatal diagnosis, to avoid termination of pregnancy for couples with a high risk of their offspring
being affected by a sex-linked genetic disease. At that time, embryos obtained in vitro were tested using
molecular techniques to ascertain the absence of a Y-bearing sequence, and only female embryos would
be transferred. Since then, techniques for molecular and cytogenetic analysis at the single-cell level,
including assessment of first and second polar bodies from oocytes or blastomeres from cleavage-stage
embryos, have evolved considerably (Sermon et al., 2004)
Techniques for genetic analysis: Polar Body Biopsy; Cleavage Stage Biopsy (most commonly used);
Trophectoderm Biopsy (less used)
PGD vs. PGS (Preimplantation genetic screening): PGD was design for an a priori fertile couple that has a
high risk of having an affected child, whereas PGS is provided for an infertile couple to detect certain
anomalies of the embryo, which might prevent a successful pregnancy. Indications are hence totally
different.
References:


ESHG and ESHRE: The need for interaction between assisted reproduction technology and
genetics - Recommendations of the ESHG and ESHRE. Eur J Hum Genet 14:509-511 (2006):
http://www.nature.com/ejhg/journal/v14/n5/abs/5201600a.html
Soini S, Ibarreta D, Anastasiadou V, Aymé S, Braga S, Cornel M, Coviello DA, Evers-Kiebooms G,
Geraedts J, Gianaroli L, Harper J, Kosztolanyi G, Lundin K, Rodrigues-Cerezo E, Sermon K,
Sequeiros J, Tranebjaerg L, Kääriäinen H, on behalf of ESHG and ESHRE. Eur J Hum Genet
14:588–645 (2006): http://www.nature.com/ejhg/journal/v14/n5/abs/5201598a.html
ESHG - European Society of Human Genetics (PPPC 2003) [13]
Need for definition: Insurance contracts laws state that the contract must be written up in utmost good
faith otherwise the contract may be void. This means that the applicant is under an obligation to reply
honestly, without withholding information. But if the definition of what can be considered genetic
information is not clear, how can an applicant reply honestly and how can an insurer ask specific
questions which are relevant to risk assessment? There is a need then for clear definitions of terms used
in genetics, insurance and employment, so that different professions and their clients have a common
understanding of the issues. A genetic test is a test of anything that is, or potentially can be, inherited
according to mendelian laws. This covers not only DNA, RNA, and chromosome analysis, but also protein
truncation test and clinical examination of a patient for a Mendelian condition that is diagnosable in that
way. But does the test result have predictive value for the subject or family members? If the answer is no,
there are no special features. If it is predictive for the subject but not the family, it is ethically similar to
several other medical tests. Only if there are also implications for the family is there a special case. It is
also important to distinguish between research and clinical genetic tests. A lot of people's worries concern
tests for disease susceptibility, and these are almost always part of research, but only clinically validated
tests should be considered for insurance purposes. Legislation without a precise definition of these terms
may confuse insurers and applicants when underwriting or renewing an insurance policy. There is a need
for clear definitions of the terms used in genetics and insurance, for the transparency of the process by
which genetic information is incorporated into insurance decisions, and for ensuring that genetic
information is not used to the detriment of other family members. There is a broad consensus that
insurance considerations should not unduly influence the uptake of appropriate clinical care, which may
30
increasingly involve genetic tests. There is also a broad consensus that applicants should not be asked to
undergo genetic tests, in order to obtain insurance.
Presymptomatic testing identifies healthy individuals who may have inherited a gene for a late-onset
disease and if so will develop the disease if they live long enough. Multifactorial diseases are frequent and
most likely triggered by specific combinations of functional DNA polymorphisms interacting with the
environment in ways that are subject to behavioral changes.
Susceptibility testing identifies healthy individuals who may have inherited a gene that puts them at
increased risk of developing a multifactorial disease, although these individuals may never develop the
disease in question. In these situations, the most that the genetic test can do is to show a propensity to a
disease.(Evans JP, Skrzynia C, Burke W: The complexities of predictive genetic testing. BMJ 2001; 322:
1052– 1056. Holtzman NA: Are we ready to screen for inherited susceptibility to cancer? Oncology 1996;
10: 57– 64)
Genetic testing classifies people into those who have the mutant gene and those who do not have it.
Now, a mutant gene is not a disease. Genetic disorders show different degrees of severity and diverge
with respect to the age of onset. Some genetic disorders affect people with near certainty but others not.
Predictions are therefore complicated by these phenomena.
Clear definitions of the terms used in genetics and insurance should be developed, so that different
professions and their clients have a common understanding of the issues. In these recommendations, the
term genetic information (of which genetic tests are a part) refers to: information that derives from the
variation between people that exists in their chromosomes or DNA, or information that is being used to
infer that a specific genetic variation or genetic influences might be present. The former includes
cytogenetic and DNA test results and very specific biochemical changes, whilst the latter category of
genetic information includes family history, clinical diagnosis, imaging, clinical chemistry test results, etc.
References:

ESHG: Genetic information and testing in insurance and employment: technical, social and
ethical issues – Recommendations of the ESHG: Eur J Hum Genet 11 Suppl 2:S11–S12 (2003):
http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201116a.pdf

Godard B, Raeburn S, Pembrey M, Bobrow M, Farndon P, Aymé S: Genetic information and
testing in insurance and employment: technical, social and ethical issues. Eur J Hum Genet 11
Suppl 2:S123–S142 (2003): http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201117a.pdf
ESHG - European Society of Human Genetics (PPPC 2003)
In the 1980s, the general objective of genetic services was more precisely defined “to help people with a
genetic disadvantage to live and reproduce as normally and as responsibly as possible”. (WHO: Report on
Community Approaches to the Control of hereditary Diseases)
Nowadays, the aim of a genetic service is often seen as to respond to the needs of individuals and families
particularly their wish to know whether or not they are at risk of developing a genetic disorder or of
bearing an affected child. A primary responsibility in genetic counselling is to provide information as
accurate as possible on diagnosis and chance or recurrence within the family.
Genetic counselling has been defined as a communication process, which deals with the human and
psychological problems associated with the occurrence, or risk of occurrence, of a genetic disorder in the
family. This process involves an attempt by one or more appropriately trained persons to help the
individual or the family to (1) understand the medical facts, including the diagnosis, the probable course
of the disorder and the available management; (2) appreciate how heredity contributes to the disorder
and the risk of recurrence in specified relatives; (3) understand the options for dealing with the risk of
recurrence; (4) choose the course of action which seems appropriate to them in view of their risk and
31
their family goals and act in accordance with that decision; and (5) make the best possible adjustment to
the disorder in an affected family member and/or to the risk of recurrence of that disorder. (Fraser FC:
Genetic Counselling, Am J Hum Genet 1974).
Presymptomatic and predictive testing: It has been demonstrated that it is in the category of
presymptomatic and predictive testing that most of the difficult issues involving genetic testing lie.33 It
should be noted that the term ‘presymptomatic testing’ is best reserved for those situations where an
abnormal test result will almost inevitably lead to development of the disease at some point in later life,
whereas the term ‘predictive testing’ covers a broader range of situations in which the risk of a disorder
occurring is substantially increased or reduced, but without necessarily implying any degree of certainty.
(Harper PS, Clarke A: Genetics Society and Clinical Practice. Bios Scientific Publishers: Oxford 1997)
References:


ESHG: Provision of genetic services in Europe: current practices and issues – Recommendations
of the ESHG. Eur J Hum Genet 11 Suppl 2:S2–S4 (2003):
http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201110a.pdf
Godard B, Kääriäinen H, Kristoffersson U, Tranebjaerg L, Coviello D, Aymé S: Provision of
genetic services in Europe: current practices and issues. Eur J Hum Genet 11 Suppl 2:S13–S48
(2003): http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201111a.pdf
ESHG - European Society of Human Genetics (PPPC 2003)
Definition of genetic screening
(1) Genetic screening may be defined as any kind of test performed for the systematic early detection or
exclusion of a genetic disease, the genetic predisposition or resistance to a disease, or to determine
whether a person carries a gene variant, which may produce disease in offspring.
(2) Screening may be concerned with the general population or with specific subpopulations defined on
some basis other than their health.
(3) Screening for genetic conditions or genetic traits predictive of diseases is a medical act. As the public
has trust in the professional duty of care, a compliance effect may be expected when a screening test is
offered, whose effect underlines the responsibility of professionals offering such tests.
(4) Genetic screening is distinguished from other types of medical screening by the genetic nature of the
disorder that may result in risk implications to family members of the person screened, even though
family members may not be, nor perhaps wish to be, included in the screening programme. Genetic
screening is also distinguished from other forms of screening because its aim is not necessarily to prevent
or treat diseases in the person screened; it may be used for health-related reproductive or lifestyle
choices.
In 1975, genetic screening had been defined as the search in a population for persons possessing certain
genotypes that (1) are already associated with disease or predispose to disease, (2) may lead to disease in
their descendants, or (3) produce other variations not known to be associated with disease.( Committee
for the Study of Inborn Errors of Metabolism: Genetic screening: programs, principles and research.
Washington, DC: National Academy of Sciences; 1975. ) Today, genetic screening may be defined as any
kind of test performed for the systematic early detection or exclusion of a hereditary disease, the
predisposition to such a disease or to determine whether a person carries a predisposition that may
produce a hereditary disease in offspring. With better knowledge of the genetics.
In 1998, the WHO has reiterated that the main objective of genetic screening is to prevent disease or
secure early diagnosis and treatment.
32
The Council of Europe has also adopted recommendations on genetic screening between 1990 and 1994.
In these recommendations, genetic screening is defined as ‘a test applied to a defined group of persons in
order to identify an early stage, a preliminary stage, a risk factor or a combination of risk factors of a
disease’. The aim of screening is ‘to cure the disease or prevent or delay its progression or onset by early
intervention’.
The Danish Council of Ethics defines genetic screening as ‘the study of the occurrence of a specific gene or
chromosome complement in a population or population group’
The Dutch Health Council defines genetic screening as ‘any kind of test performed for the systematic early
detection or exclusion of a hereditary disease, the predisposition to such a disease or to determine
whether a person carries a predisposition that may produce a hereditary disease in offspring’.
References:


ESHG: Population genetic screening programmes: technical, social and ethical issues –
Recommendations of the ESHG. Eur J Hum Genet 11 Suppl 2:S5–S7(2003):
http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201112a.pdf
Godard B, ten Kate L, Evers-Kiebooms G, Aymé S: Population genetic screening programmes:
principles, techniques, practices, and policies. Eur J Hum Genet 11 Suppl 2:S49–S87 (2003):
http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201113a.pdf
ESHG - European Society of Human Genetics (PPPC 2003)
The American National Bioethics Advisory Commission defined a DNA bank as ‘a facility that stores
extracted DNA, transformed cell lines, frozen blood or other tissue, or biological materials, for future DNA
analysis’. The same Commission defined a DNA databank as ‘a repository of genetic information obtained
from the analysis of DNA, sometimes referred to as ’DNA profiles’. The genetic information is usually
stored in computerized form with individual identifiers’.
Reference:

Godard B, Schmidtke J, Cassiman JJ, Aymé S: Data storage and DNA banking for biomedical
research: informed consent, confidentiality, quality issues, ownership, return of benefits. A
professional perspective. Eur J Hum Genet 11 Suppl 2:S88–S122 (2003):
http://www.nature.com/ejhg/journal/v11/n2s/pdf/5201114a.pdf
ESHRE - European Society of Human Reproduction and Embryology
Reference:

See ESHG and ESHRE (PPPC 2006)
Documents, but no definitions found.
ENGCN - European Network of Genetic Counsellors and Nurses
Documents, but no definitions found.
33
BSHG - British Society of Human Genetics (Joint Committee on Genetic Testing 2011)
See RCP - Royal College of Physicians, Royal College of Pathologists and British Society for Human
Genetics (Joint Committee on Genetic Testing 2011).
AGNC - Association of Genetic Nurses and Counsellors, UK
Documents, but no definitions found.
HGAC - Human Genetics Advisory Commission, UK
Genetic testing - testing to detect the presence or absence of, or alteration in, a particular gene
sequence, chromosome or a gene product, in relation to a genetic disorder.

Diagnostic genetic testing - use of genetic testing in a person with disease symptoms to aid in
their diagnosis, treatment and management.

Presymptomatic genetic testing - testing of healthy or asymptomatic individuals to provide
information about that individual's future risk of certain specific inherited diseases. Such a test
may indicate that the individual has a higher likelihood of developing a disorder. Presymptomatic
genetic testing is most frequently offered to those thought to be at high risk of autosomal
dominant disorders such as Huntington's disease.

Carrier testing - testing of unaffected individuals to determine whether they are carriers of a
gene for a recessively inherited disorder (e.g. cystic fibrosis) and are thus at risk of having an
affected child.

Susceptibility testing - testing which provides information about a genetic component in a
multifactorial disorder. Multifactorial disorders are disorders whose genetic components are not
the sole cause, but which work with other, often environmental factors, in determining a disease
outcome. Multifactorial disorders include many cardiovascular diseases, most Alzheimer's
disease of old age and most forms of diabetes.
The use of genetic testing for biological monitoring (i.e. as a dosimeter to monitor DNA damage due to
environmental effects) is not considered in this report.
Genetic screening - a term used to denote application of genetic tests to populations of people, who
individually are not at particularly high risk. In contrast, genetic testing of individuals is undertaken when
there is some specific prior reason to suspect that the person being tested may be at higher than average
risk of carrying the gene change being tested for.
Reference:

The Implications of Genetic Testing for Employment:
http://www.advisorybodies.doh.gov.uk/hgac/papers/papers_g/g_03.htm
ASHG, American Society of Human Genetics [14]
Genetic testing is a means of looking for changes or abnormalities in an individual’s genes or gene
products (e.g., proteins). The purpose is to determine if someone has a genetic condition or is likely to get
a specific disorder. Typically a person may be offered testing if they have a family history of a specific
34
disease; they have symptoms of a genetic disorder; or they are concerned about passing a genetic
disorder to their offspring. Genetic testing is voluntary, and the testing has both benefits and limitations.
Reference:

Genetic Testing: http://www.ashg.org/education/genetic_testing.shtml
ASHG, American Society of Human Genetics (2000)
From our perspective, there are problems with the definition of what exactly constitutes a "genetic test"
that should require additional oversight. We suggest restricting the definition of genetic tests that would
require additional oversight to those that test for a particular nucleotide sequence directly or indirectly.
This would include all DNA and RNA testing, protein truncation and similar tests of expression that are
based on DNA or RNA sequence, and FISH or equivalent kinds of molecular cytogenetic testing. While
many genetic diseases can be diagnosed equally well by looking at a gene product, it appears that tests
involving nucleotide sequence are the ones that generate particular concern among non-geneticist health
professionals and the public, and it is this concern that justifies additional oversight.
Reference:

ASHG Response to Request for Public Comments on Preliminary Final Recommendations on
Oversight of Genetic Testing. May 22, 2000:
http://www.ashg.org/pages/statement_5222000.shtml
ASHG, American Society of Human Genetics (ACGT 1995)
The Problem of Defining Genetic Conditions and Tests: Definitions can become important when insurance
policies and laws distinguish genetic conditions and genetic tests from other medical conditions and tests.
While some conditions (e.g., Tay-Sachs disease) have a virtually purely genetic basis, most genetic
disorders involve an interaction between a genetic predisposition and environmental factors. Even singlegene disorders (e.g., sickle-cell disease and cystic fibrosis) have variable expression depending in part on
such environmental factors as oxygen tension in the former and nutritional factors in the latter. Similarly,
some tests, such as those involving mutation analysis, might seem to be clearly genetic tests, but many
others, used to test for genetic disorders, measure gene products or further-removed effects. The latter
include many tests that could be considered genetic tests, such as Guthrie spots, which test for elevated
levels of phenylalanine, or any X-ray used to diagnose or rule out achondroplasia. The point of these
observations is that there is no clear boundary between genetic and nongenetic conditions and tests.
…
Until universal access is reality, genetic testing and genetic diagnosis will raise important issues for the
practicing geneticist. How much does a client need to know about insurance implications before
consenting to a genetic test? Should patients be counseled to purchase insurance before being tested?
Should genetic information be excluded from medical records before their release to insurance
companies for routine reimbursements or underwriting? What are the ethical and legal responsibilities of
the geneticist?
Reference:

Genetic Testing and Insurance - background statement. The Ad Hoc Committee on Genetic
Testing/Insurance Issues, Am J Hum Genet 56:327-331(1995):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=782559
4
35
NSGC - National Society of Genetic Counselors, US (2007; revised 2011)
DIRECT TO CONSUMER GENETIC TESTING: Genetic testing is currently available to consumers without the
involvement of the patients’ healthcare providers. A growing number of ‘Direct to Consumer’ (DTC)
genetic testing companies offer tests that may diagnose genetic conditions or carrier status, and/or tests
that aim to predict a person’s chances of developing certain medical disorders. In addition, DTC genetic
analysis is available for various non-medical purposes such as ancestry, marketing of “nutrigenomics”
products or paternity testing.
The National Society of Genetic Counselors (NSGC) recognizes that DTC genetic testing may increase
access to medical testing services for some individuals. However, individuals seeking genetic information
directly from a manufacturer or supplier and without input from a healthcare provider may lack basic and
essential knowledge of the purpose and appropriateness of testing, the accuracy and clinical
significanceof results for themselves and other family members, or the reliability of the laboratory.
There is limited regulatory oversight of DTC genetic testing services at this time. In order to increase the
likelihood that patients receive appropriate genetic testing services through a DTC service delivery model,
the NSGC strongly recommends that patients undertaking a direct to consumer genetic testing process
assess whether the company has addressed the following issues prior to purchasing a DTC genetic test:

Are consumer-friendly materials available, developed or reviewed by healthcare professionals
with expertise in genetics (e.g. trained genetic counselors) and suitable for individuals seeking
and receiving direct-to-consumer testing services?

Is information disclosed to potential consumers regarding test purpose, potential limitations,
validity and accuracy, using language that is written for consumers?

Will results be given in a manner understandable to the average consumer, with a clear
explanation of their clinical implications, if any, and including resources providing appropriate
follow-up?

Are patients encouraged to share their medically relevant genetic test results with their
healthcare providers and family members who may also be at risk?

Are consumer referrals to healthcare professionals with expertise in genetics available, either on
staff or independent of the commercial entity, both before and after testing to assure
appropriate medical follow up, including psychological counseling as needed?

Is there a process for obtaining and documenting informed consent in a manner consistent with
accepted medical practices as well as state and local regulations?

What safeguards are in place to protect the consumer/patient privacy?

Has the company implemented policies that adhere to testing guidelines and position statements
of professional organizations, including the National Society of Genetic Counselors, the American
College of Medical Genetics, American Society of Human Genetics and others? These may include
relevant guidelines for genetic testing of minors or other potentially vulnerable populations.

Are the genetic tests performed by appropriately credentialed laboratories (e.g. CLIA certified)?
NSGC supports consumers’ right to access high-quality genetic services, strongly encourages the
involvement of appropriately trained clinical genetics professionals in the genetic testing process, and
cautions against using DTC commercial entities that have not addressed the basic issues outlined above.
Reference:

Position Statements (US National Society of Genetic Counselors):
http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx
36
NSGC - National Society of Genetic Counselors, US (2010)
REGULATION OF GENETIC TESTING: Genetic testing is rapidly transitioning from identifying the genetic
causes of rare conditions to also providing personalized risk assessments and individual treatments for
common diseases. With this expansion, the expertise of Board-certified genetics professionals, such as
genetic counselors, may not always be utilized for tests applied to the general population.
The NSGC supports regulation that protects patients from harm by assessing the risk of genetic tests in
the context of: 1) the expertise of the health professional providing testing and interpretation; 2) uses or
intended applications of test results; and 3) evidence of clinical validity and utility. (Adopted 2010)
REPRODUCTIVE FREEDOM: NSGC supports the right of all individuals and couples to make reproductive
choices. These include using information from genetic counseling and/or testing to decide whether to
pursue a pregnancy, to utilize assisted reproductive technologies, to prepare for the birth and future
needs of their offspring, to make an adoption plan, or to end a pregnancy. NSGC firmly believes that
reproductive decisions should be made in the context of unbiased and comprehensive information, free
from discrimination or coercion.
Reference:

Position Statements (US National Society of Genetic Counselors):
http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx
NSGC - National Society of Genetic Counselors, US (2006)
The Genetic Counseling Definition Task Force of the National Society of Genetic Counselors (NSGC)
developed the following definition of genetic counseling that was approved by the NSGC Board of
Directors:
Genetic counseling is the process of helping people understand and adapt to the medical, psychological
and familial implications of genetic contributions to disease. This process integrates the following:
•Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence.
•Education about inheritance, testing, management, prevention, resources and research.
•Counseling to promote informed choices and adaptation to the risk or condition.
The definition was approved after a peer review process with input from the NSGC membership, genetic
professional organizations, the NSGC legal counsel, and leaders of several national genetic advocacy
groups.
Reference:

Resta R, Biesecker BB, Bennett RL, Blum S, Hahn SE, Strecker MN, Williams JL (2006): A New
Definition of Genetic Counseling: National Society of Genetic Counselors’ Task Force Report.
DOI: 10.1007/s10897-005-9014-3; J Genet Counsel 15 (2):77-83, 2006
NSGC - National Society of Genetic Counselors, US (2002)
GENETIC TESTING AND ADOPTION: The National Society of Genetic Counselors supports the American
Society of Human Genetics and the American College of Medical Genetics joint statement written in the
year 2000 entitled “Genetic Testing in Adoption” with the addition of the following comments:
37
The NSGC supports the routine collection of accurate family, genetic, and medical history information for
children entering into the adoption process or foster care system. Medical professionals should utilize this
information to determine the likelihood of specific genetic conditions and the appropriateness of genetic
testing for the child. Genetic testing should not be undertaken unless family, genetic or medical histories
indicate that the results have the potential to be of timely benefit to the child. As previously outlined in
the American Society of Human Genetics Social Issues Committee Report on Genetics and Adoption:
Points to Consider, 1991
In the unlikely event that genetic testing reveals information that is not of timely medical relevance this
specific information should only be released to adoptive parents once the adoption is finalized. Education
and counseling throughout the consent and genetic testing process by an appropriate professional is
essential.
Reference:

Position Statements (US National Society of Genetic Counselors):
http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx
NSGC - National Society of Genetic Counselors, US (1997)
GENETIC TESTING FOR ADULT-ONSET DISORDERS: Predisposition genetic testing for hereditary
susceptibility to disease is a new arena of medicine, but is likely to affect increasing numbers of person
and families as more genes are identified. NSGC advocates responsible testing, whether commercial or
non-commercial, for which persons receive appropriate pretest education and genetic counseling and
posttest follow-up care, as outlined in the position paper. In addition, it is recommended that
professionals offering such testing establish relationships with laboratories providing testing to optimize
testing procedures and the clinical interpretation of test results. Caution must be used in the provision of
predisposition genetic tests to protect persons and families from potential risks to autonomy, privacy, and
justice, while maximizing the benefits from genetic knowledge to the individual and to society.
Reference:

Position Statements (US National Society of Genetic Counselors):
http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx
NSGC - National Society of Genetic Counselors, US (1995)
PRENATAL AND CHILDHOOD TESTING FOR ADULT-ONSET DISORDERS: Adult-onset genetic disorders are
defined as disorders which are usually phenotypically asymptomatic until the third decade of life or later.
For those disorders for which the identification of gene carriers does not provide an avenue for
therapeutic or preventive treatment in the prenatal or childhood periods, genetic testing must be
carefully considered. In response to the unique nature of these disorders, the NSGC supports the
following recommendations: Clients considering a pregnancy or who have a fetus or child at-risk for an
adult-onset genetic disorder should be made aware of clinically available testing technologies for that
disorder.
Testing during pregnancy or childhood allows the parent, rather than the individual (fetus or child) being
tested, to provide informed consent to proceed. Given that many at-risk adults may elect not to be tested,
testing in pregnancy or during childhood should be undertaken cautiously. Parents should consider
whether the decision to test should be reserved for the child to make upon reaching adulthood.
38
Prenatal and childhood testing for adult-onset genetic conditions should always include genetic education
and counseling. Genetic counseling for clients considering such testing should include exploration of the
psychological/social risks and benefits of early genetic identification from both the parents' and child's
perspectives. When possible the child should be involved in the decision about whether or not to be
tested. Other issues discussed should include the possibility of discrimination in insurance, education and
employment for the child or family in both the immediate and more distant future.
Prenatal testing for adult-onset genetic conditions should be offered regardless of whether or not an
affected fetus would be terminated. Prior to prenatal testing, genetic counselors should discuss the
possible results as well as advantages and disadvantages of learning this information. It may also be
helpful to ascertain and discuss the parent's motivations for testing. It is the role of the genetic counselor
to educate and counsel clients about testing, but the decision about whether to proceed must be the
parents' to make.
Individuals who have declined predictive testing for themselves can consider testing for their child or
fetus, or utilizing non-disclosing prenatal testing. However, prior to performing such testing, they must be
made cognizant to the fact that (with the exception of non-disclosing prenatal testing) a positive result
may also disclose their status. Discussion of the possible ramifications of this information should be
included in the genetic counseling provided prior to testing. If prenatal or childhood testing could result in
the disclosure of the carrier status of family members who are not part of the testing decision process,
attempts should be made to contact, counsel and obtain their permission for testing. If a conflict should
arise between parents and other at-risk family members, consultation with an ethics committee or similar
body is strongly recommended.
Caution should be exercised in the communication and documentation of test results. The child's parents
should be made aware of the sensitive nature of the test results and the implications of sharing them with
other professionals for whom the information is non-essential.
Genetic counselors are encouraged to consider both patient autonomy issues as well as the principle of
nonmaleficence when requests are made for this type of testing. As with any type of genetic testing and
counseling situation, genetic counselors should not be expected to offer a service that they feel
uncomfortable providing and should be allowed to remove themselves from such a case, or refer the case
to another genetics professional.
Pilot studies are needed to assess the medical and psychosocial risks and benefits of testing for adultonset genetic conditions in children or fetuses carried to term when no direct medical benefit is known.
Until more data is gathered on the impact of this type of testing, extreme caution should be taken
regarding the use of such tests.
Reference:

Position Statements (US National Society of Genetic Counselors):
http://www.nsgc.org/Advocacy/PositionStatements/tabid/107/Default.aspx
ACMG - American College of Medical Genetics [15]
Genetic Testing
What is genetic testing?
Genetic testing is the examination of an individual's chromosomes, genes, proteins and/or other analytes
for alterations associated with genetic disorders or conditions.
What is genetic testing used for?
Genetic testing can be used to diagnose a genetic disorder in a person showing signs (symptoms) of the
disorder (diagnostic testing); to determine whether an individual is at increased risk for having a child with
39
a particular genetic disorder (carrier testing); to determine whether a fetus is affected by a particular
genetic disorder (prenatal testing); to determine before implantation whether an embryo will be affected
by a particular genetic disorder (preimplantation genetic diagnosis); to assess an individual's risk for
developing a particular genetic disorder at some time in the future (presymptomatic genetic testing,
cancer genetic testing); or, to select an appropriate course of treatment for a patient (pharmacogenetic or
presymptomatic genetic testing, cancer genetic testing). There are also genetic tests to determine
parentage, typically paternity (paternity testing), and personal identity (forensic DNA analysis or DNA
fingerprinting); identify acquired genetic changes such as those associated with cancer; and, predict the
success of transplantation procedures.
What types of samples can be used for genetic testing?
Genetic testing laboratories use a variety of different types of samples for genetic testing. Many genetic
tests require a blood sample, but urine, amniotic fluid, chorionic villus sampling (CVS), cheek swab, tissue
sample or biopsy, hair, or semen can also be used. The type of sample required depends upon the type of
test that is to be performed and the techniques used by the testing laboratory.
What are the benefits of genetic testing?
Medical genetic tests may provide a definitive diagnosis of a genetic disorder, identify one's risk for
developing a particular genetic disorder, or determine whether an individual is at risk for having a child
with a particular genetic disorder. In cases where a patient has symptoms that are suggestive of a
disorder but not definitive, genetic testing may help in reaching a diagnosis.
Medical genetic tests may also help with genetic counseling of patients and their families so that family
members can learn what genetic disorder is occurring in their family, identify their risks for developing the
disorder, and understand their risks for having children with the disorder.
Medical genetic tests can also sometimes help predict the severity of a disorder or determine the best
course of treatment for a patient.
If negative, medical genetic tests may rule out a particular genetic disorder in a patient or allow for
recalculation of the risk that a particular genetic disorder might occur in an individual or their children.
What are the limitations of genetic testing?
Most medical genetic tests are specific for a particular disorder and cannot identify disorders not directly
tested. For example, a molecular genetic test for cystic fibrosis will not identify genetic alterations
associated with Down syndrome. Alternatively, a chromosome analysis (karyotype) can detect a number
of conditions caused by abnormalities in the number or arrangement of chromosomes such as Down
syndrome or Turner syndrome but a karyotype will not diagnose cystic fibrosis. The type of medical
genetic test ordered for a patient must take into account the patient's symptoms, concerns, family
medical history, and/or ancestry, and be appropriate for the genetic condition in question.
Although medical genetic tests can often help with the diagnosis of a genetic disorder, they may not
always be able to predict the age of onset or severity of a disorder, or determine the best course of
treatment for a patient.
If negative, medical genetic tests may offer limited information leaving the doctor, patient, and family
knowing little more than they did before the test.
What are the risks of genetic testing?
The physical risks associated with genetic testing are typically small, especially if the test being ordered
requires only a blood or urine sample, or a cheek swab. However, in cases where tissue samples or
biopsies are required the physical risks of the test may be higher and will depend on the type of sample
that is required and how it must be obtained. In the case of prenatal testing, some tests such as chorionic
villus sampling (CVS), amniocentesis, or fetal blood sampling (cordocentesis) have a small risk of
miscarriage (losing the pregnancy), while other tests such as fetal ultrasonography do not.
40
There can be emotional and social consequences associated with genetic testing such as feelings of anger,
guilt, anxiety, or depression. These feelings can affect the individual being tested and their relatives,
particularly if the test results reveal a previously unsuspected risk for a genetic disorder or if some
relatives do not want to know the results of the genetic tests. In some cases, genetic tests can also reveal
previously unknown information about familial relationships such as nonpaternity or undisclosed
adoption. These potential consequences of genetic testing can complicate the relationships within
families.
Some people have concerns about financial consequences of genetic testing such as the potential for
discrimination in or loss of employment or insurance. In May, 2008, the Genetic Information
Nondiscrimination Act (GINA) was signed into federal law. GINA offers protection against genetic
discrimination in health insurance and employment. For more information about GINA, visit the website
of the Coalition for Genetic Fairness.
Talk to your clinical geneticist or genetic counselor if you have concerns about the potential risks of
genetic testing.
Reference:

American Collegue of Medical Genetics, Genetics Frequently Asked Questions:
http://www.acmg.net/AM/TextTemplate.cfm?Section=Genetics_Frequently_Asked_Questions
_GFAQs_&Template=/CM/HTMLDisplay.cfm&ContentID=3073
ABMG - American Board of Medical Genetics
No documents relating to genetic testing were found.
ABGC - American Board of Genetic Counseling (2006)
The ABGC adopted the NSGC Definition of Genetic Counseling (J Genet Counsel, April
2006; 77-82).
Reference:

Genetic Counselors’ Scope of Practice:
http://www.abgc.net/docs/GC_Scope_of_prractice_final.pdf
CORN - Council of Regional Networks for Genetic Services (1997)
Genetic counseling – A communication process which deals with human problems associated with the
occurrence, recurrence or the risk thereof, of a genetic disorder within a family. This process involves an
attempt by one or more appropriately trained persons to help the individual or family: (1) comprehend
the medical facts, including the diagnosis, the probable course of the disorder, and the available
management; (2) appreciate the way heredity contributes to the disorder, and the risk of recurrence in
specified relatives; (3) understand the options for dealing with the risk of recurrence; (4) choose the
course of action which seems most appropriate to them in view of their risk and the family goals and act
in accordance with that decision; and (5) make the best possible adjustment to the disorder in an affected
family member and/or to the risk of recurrence of that disorder. Reassurance that an individual is NOT at
41
risk for the occurrence or recurrence of a disorder is also an inseparable component of genetic
counselling.
Genetic diagnosis/evaluation – the process of determining the presence or absence of a condition
through physical evaluation and/or laboratory testing. Once a diagnosis has been made, appropriate
genetic counselling can be performed and an acceptable treatment plan developed. Diagnostic
procedures performed that focus on a foetus are referred to as prenatal services while all others are
referred to as clinical services. The clinical evaluation and diagnostic process is typically performed by a
physician who is certified by the American Board of Medical Genetics as a clinical geneticist, while
prenatal evaluation and diagnostic testing may be performed by an obstetrician/perinatologist, in
consultation with genetic professionals as needed.
Genetic screening – A process by which an individual undergoes a procedure and/or test to indicate if
they are at greater or lesser risk than the general population for having a specific condition. If a positive
screening result is encountered, the individual is typically referred for diagnostic (confirmatory) testing.
Current examples of genetic screening include newborn screening for PKU, or maternal serum alphafetoprotein screening during pregnancy to identify foetuses with spina bifida or Down syndrome.
Genetics – The branch of biology which deals with heredity and variation: Human Genetics – The branch
of biology which deals with heredity and variation in the human species; Medical Genetics – The
application of human genetics to diseases and abnormalities of human development; Clinical Genetics –
The provision of medical services to individuals, families and populations who have or are at risk for
disorders with genetic implications.
Reference:

Guidelines for Clinical Genetic Services for the Public’s health, Council of Regional Networks for
Genetic Services (1997): http://genes-r-us.uthscsa.edu/resources/pdf/geneticguidelns.pdf
HGSA - Human Genetics Society of Australasia (2009)
Presymptomatic and predictive testing refers to a test performed on a person with a family history of a
heritable disorder and who lacks symptoms or signs of the disorder with the objective being to determine
whether the person has inherited the mutation responsible.
References:


Presymptomatic and Predictive Testing for Genetic Disorders (8 Dec 2009): permalink:
/2009/12/presymptomatic-and-predictive-testing-for-genetic-disorders
Prioritising Genetic Tests (May 2009): https://www.hgsa.org.au/website/wpcontent/uploads/2009/12/2009GL03-Prioritising-Genetic-Tests.pdf
HGSA - Human Genetics Society of Australasia (2008)
For the purpose of this document:
 "predictive genetic information" is taken to mean a refinement of risk for an individual based on the
measurement of specific genotype(s) ("predictive genetic test(s)") and not risk that could be deduced
by reference to a family history alone.
 "insurance" can be considered to include life insurance, disability insurance and crisis/trauma
insurance but not health insurance while the latter remains subject to Section 73(2A) of the
Commonwealth's National Health Act (1953) which precludes refusal to insure persons by reason of
their state of health.
42
 "adverse selection" is a term used in the insurance industry to describe the situation in which the
distribution of risk in the pool of insured individuals is skewed adversely as, for example, when a high
risk group selectively takes out insurance or seeks abnormally high insurance cover.
Reference:

Genetic Testing and Life Insurance in Australia: https://www.hgsa.org.au/website/wpcontent/uploads/2009/12/2008PS01-Genetic-testing-and-life-insurance.pdf
HGSA - Human Genetics Society of Australasia (2007)
Categories of genetic testing
 carrier testing, where the implications are usually for reproduction options
 diagnostic testing, for the benefit of the person who is already symptomatic or for whom treatment is
required
 pre-symptomatic testing where the identification of a specific mutated gene means the person is
almost certain to develop the condition during their lifetime (if they live long enough), and
 predictive testing where the person with the mutated gene has an inherited predisposition to develop
the condition i.e. is at increased risk but may never develop the condition unless other factors are
present.
References:


Protection of Human Genetic Information (Jul 2007): https://www.hgsa.org.au/website/wpcontent/uploads/2009/12/2007GD01-Protection-of-Human-genetic-Information.pdf
Direct to Consumer Genetic Testing (July 2007): https://www.hgsa.org.au/website/wpcontent/uploads/2009/12/2007IP01-Direct-to-Consumer-Testing.pdf
HGSA - Human Genetics Society of Australasia (1999)
Genetic Counsellor-A health professional with specialised training in genetics and counselling who can
provide information and support to individuals or families with concerns about a genetic disorder that
may run in the family. Those genetic counsellors who have not completed their training usually denote
themselves as Associate genetic counsellors.
The process of genetic counselling is complex as it is a communication process which involves making or
discussing a diagnosis, providing accurate information about the disorder and options available to the
client, and considering the impact the information has on clients and their families. Harper defines genetic
counselling as “the process by which patients and relatives at risk of a disorder that may be hereditary are
advised of the consequences of the disorder, the probability of developing or transmitting it and of the
ways in which this may be prevented, avoided or ameliorated”. (Peter S. Harper (1998) “Practical Genetic
Counselling” Butterworth-Heinemann. Oxford)
Diagnostic test: A diagnostic test is usually ordered by a clinical geneticist to make or confirm a suspected
diagnosis, or to exclude a differential diagnosis. A clinical diagnosis or ordering a genetic test is reliant
upon the judgement and expertise of the clinical geneticist and is within his/her responsibility. Geneticists
may delegate the responsibility of arranging a genetic test to a genetic counsellor with appropriate
supervision. A prenatal test may be a diagnostic test when carried out on a developing fetus.
Genetic carrier testing: A test to determine if an individual, with or without symptoms, has a genetic
mutation or a chromosome abnormality, which increases the chance of his/her children, having the
43
disorder in question. The term carrier is used with respect to autosomal recessive and X-linked genes and
balanced chromosome rearrangements.
Screening tests: Screening tests are non-diagnostic, population-based tests providing the client with a
personalised risk. When performed prenatally, screening tests may identify fetal abnormalities or reveal
an increased risk of fetal abnormalities. When performed post-natally, the aim of genetic screening is to
identify individuals at increased risk of developing symptoms of a disorder in the future, with a view to
offering intervention eg, newborn screening. The nature of a screening test should be clearly
distinguished from a diagnostic test to the client. Appropriate written and/or verbal information should
be provided prior to testing. Support and counselling should be made available to persons receiving a
high-risk result so that future options are understood.
Predictive/pre-symptomatic tests: These tests are performed on an individual who has no symptoms of a
specific disorder at the time of testing, to determine whether he/she has a mutant gene. If the mutant
gene(s) is present the individual is at a increased probability of developing symptoms at sometime in the
future. Guidelines for predictive/pre-symptomatic testing for late- onset disorders have been developed
by the HGSA.
Research tests: Tests carried out as part of a research study supported by special funding approved by an
institutional ethics committee. The NHMRC's National Statement on Ethical Conduct in Research Involving
Humans (1999) provides guidelines for genetic testing when performed as part of a research study.
Presymptomatic testing refers to a genetic test performed on a person who has a family history but no
symptoms of a specific disorder at the time of testing, to determine whether or not the mutation for that
disorder (known to be present in the family) has been inherited.
If the test reveals that the mutation is present, the person is almost certain to develop the disorder at
some time in the future, provided he or she lives long enough. Huntington disease, familial adenomatous
polyposis (FAP) and myotonic dystrophy are examples of disorders to which the term ‘presymptomatic’
testing applies.
Predictive testing refers to a genetic test performed on a person who has a family history but no
symptoms of a specific disorder at the time of testing, to determine whether or not the mutation for that
disorder (known to be present in the family) has been inherited.
If the test reveals that the mutation is present, the person has an increased probability, rather than
certainty, of developing the disorder at some time in the future, provided he or she lives long enough.
Testing for mutations in BRCA1 and BRCA2 (breast cancer) and MLH1 and MSH2 (colon cancer) are
examples of predictive testing. (NHMRC (2000). Ethical Aspects of Human Genetic Testing: An Information
Paper. www.nhmrc.health.gov – publications/ethics/human)
There are three categories of Genetic testing:
 Carrier testing, where the implications are usually for reproduction
 Diagnostic testing, for the benefit of the person who is already symptomatic or for whom
treatment is required and
 Predictive testing, where the test predicts the onset of a disease at some future time.
Reference:

Privacy Implications of Genetic Test (1999):
http://hgsa.com.au/images/UserFiles/Attachments/PrivacyImplicationsofGeneticTesting1.pdf
44
5. Other Genetics Organizations
HGP - Human Genome Project (2010) [16]
What is gene testing? How does it work?
Gene tests (also called DNA-based tests), the newest and most sophisticated of the techniques used to
test for genetic disorders, involve direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic examination of stained or fluorescent chromosomes. Genetic tests are used for several reasons, including:

carrier screening, which involves identifying unaffected individuals who carry one copy of a gene
for a disease that requires two copies for the disease to be expressed
 preimplantation genetic diagnosis (see the side bar, Screening Embryos for Disease)
 prenatal diagnostic testing
 newborn screening
 presymptomatic testing for predicting adult-onset disorders such as Huntington's disease
 presymptomatic testing for estimating the risk of developing adult-onset cancers and
Alzheimer's disease
 confirmational diagnosis of a symptomatic individual
 forensic/identity testing
In gene tests, scientists scan a patient's DNA sample for mutated sequences. A DNA sample can be
obtained from any tissue, including blood. For some types of gene tests, researchers design short pieces
of DNA called probes, whose sequences are complementary to the mutated sequences. These probes will
seek their complement among the three billion base pairs of an individual's genome. If the mutated
sequence is present in the patient's genome, the probe will bind to it and flag the mutation. Another type
of DNA testing involves comparing the sequence of DNA bases in a patient's gene to a normal version of
the gene. Cost of testing can range from hundreds to thousands of dollars, depending on the sizes of the
genes and the numbers of mutations tested.
Reference:

Human Genome Project Information: Gene Testing:
http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetest.shtml
HUGO - Human Genome Organization
Documents, but no definitions found.
ORPHANET - The Portal for Rare Diseases and Orphan Drugs
Documents, but no definitions found.
EDDNAL - European Directory of DNA Diagnostic Laboratories
Documents, but no definitions found.
45
GeneTests (2004) [17]
(funded and supported by University of Washington, Seattle, National Library of Medicine, NIH, National
Human Genome Research Institute, NIH)
WHAT IS GENETIC TESTING?
A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order
to detect alterations related to a heritable disorder. This can be accomplished by directly examining the
DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing
gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes
(cytogenetic testing). Selected methodology terms are used in the GeneTests Laboratory Directory.
Although genetic testing shares some features in common with other kinds of laboratory testing, in many
ways it is unique and requires special considerations.
Points to consider: Genetic testing may be used for medical management and for personal decisionmaking. Genetic test results usually apply not only to the patient but also to other family members.
Genetic testing may be performed in the context of a genetics consultation and should include informed
consent, test interpretation, and follow-up medical and psychosocial services as indicated. Because most
genetic disorders are rare, genetic testing is often done only by specialized laboratories. Intense research
efforts in molecular genetics result in the rapid development and availability of new genetic tests;
therefore, healthcare providers need to continuously update their knowledge. In order for genetic testing
to yield meaningful results: multiple test methodologies may be required; other family members may
need to be tested; a genetics consultation may be appropriate. These services will entail additional costs.
What is a Clinical Test?
Clinical tests are those in which specimens are examined and results reported to the provider or patient
for the purpose of diagnosis, prevention or treatment in the care of individual patients.
Points to consider: United States laboratories performing clinical tests must be CLIA approved. There is a
charge for clinical tests; cost varies by complexity. Test results are reported in writing. The time between
specimen submission and reporting of results varies between laboratories and may be based in part on
the complexity of the testing.
What is a Research Test?
Research tests are those in which specimens are examined for the purpose of understanding a condition
better, or developing a clinical test.
Points to consider: Laboratories performing research testing are not subject to CLIA regulation. The cost
of research testing is generally covered by the researcher. Test results are generally not given to patients
or their providers. Rarely, a research laboratory will, at the patient's request, share potentially useful
findings with a clinical laboratory so the patient's test results can be confirmed and a formal report issued.
Requests for participation in research may be denied, at the laboratory's discretion, if the laboratory has
sufficient samples or the family does not fit the research project goals.
What is an Investigational Test?
Investigational tests are deemed to be of value but not yet scientifically valid or generally accepted by the
medical community as accurate and useful.
Points to consider: Test results may or may not be shared, and it may be a long time before results are
available. If test results are shared with the provider or patient, the laboratory must be CLIA approved.
There may or may not be a cost for testing.
GeneTests asks that each laboratory define its testing as "Clinical" or "Research." We acknowledge the
category "Investigational," which is used by some laboratories, but it is too loosely defined to be very
helpful to our users. Some tests listed in GeneTests as "Research" may fall into the "Investigational"
category.
46
USES OF GENETIC TESTING
Diagnostic testing is used to confirm or rule out a known or suspected genetic disorder in a symptomatic
individual.
Points to consider: DNA testing may yield diagnostic information at a lower cost and with less risk than
other procedures. Diagnostic testing is appropriate in symptomatic individuals of any age. Confirming a
diagnosis may alter medical management for the individual. Diagnostic testing of an individual may have
reproductive or psychosocial implications for other family members as well. Establishing a diagnosis may
require more than one type of genetic test. DNA testing may not always be the best way to establish a
clinical diagnosis.
Predictive testing is offered to asymptomatic individuals with a family history of a genetic disorder.
Predictive testing is of two types: presymptomatic (eventual development of symptoms is certain when
the gene mutation is present, e.g., Huntington disease) and predispositional (eventual development of
symptoms is likely but not certain when the gene mutation is present, e.g., breast cancer).
Points to consider: Predictive testing is medically indicated if early diagnosis allows interventions which
reduce morbidity or mortality. Even in the absence of medical indications, predictive testing can influence
life planning decisions. Because predictive testing can have psychological ramifications, careful patient
assessment, counseling, and follow-up are important. Many laboratories will not proceed with predictive
testing without proof of informed consent and genetic counseling. Identification of the specific gene
mutation in an affected relative or establishment of linkage within the family should precede predictive
testing. Predictive testing of asymptomatic children at risk for adult onset disorders is strongly
discouraged when no medical intervention is available.
Carrier testing is performed to identify individuals who have a gene mutation for a disorder inherited in
an autosomal recessive or X-linked recessive manner. Carriers usually do not themselves have symptoms
related to the gene mutation. Carrier testing is offered to individuals who have family members with a
genetic condition, family members of an identified carrier, and individuals in ethnic or racial groups
known to have a higher carrier rate for a particular condition.
Points to consider: Identifying carriers allows reproductive choices. Genetic counseling and education
should accompany carrier testing because of the potential for personal and social concerns. Molecular
genetic testing of an affected family member may be required to determine the disease-causing
mutation(s) present in the family. In some situations, DNA testing may not be the primary way of
determining carrier status. Carrier testing can improve risk assessment for members of racial and ethnic
groups more likely to be carriers for certain genetic conditions.
Prenatal testing is performed during a pregnancy to assess the health status of a fetus. Prenatal
diagnostic tests are offered when there is an increased risk of having a child with a genetic condition due
to maternal age, family history, ethnicity, or suggestive multiple marker screen or fetal ultrasound
examination. Routine prenatal diagnostic test procedures are amniocentesis and chorionic villus sampling
(CVS). More specialized procedures include placental biopsy, periumbilical blood sampling (PUBS), and
fetoscopy with fetal skin biopsy.
Points to consider: A laboratory that performs the disease-specific test of interest must be identified
before any prenatal diagnostic test procedure is offered. All prenatal diagnostic test procedures have an
associated risk to the fetus and the pregnancy; therefore, informed consent is required, most often in
conjunction with genetic counseling. In most cases, before prenatal diagnosis using molecular genetic
testing can be offered, specific gene mutation(s) must be identified in an affected relative or carrier
parent(s).
Prenatal testing for adult-onset conditions is controversial. Individuals seeking prenatal diagnosis for
these conditions should be referred to a professional trained in genetic counseling for a complete
discussion of the issues.
47
Preimplantation testing is performed on early embryos resulting from in vitro fertilization in order to
decrease the chance of a particular genetic condition occurring in the fetus. It is generally offered to
couples with a high chance of having a child with a serious disorder. Preimplantation testing provides an
alternative to prenatal diagnosis and termination of affected pregnancies.
Points to consider: Preimplantation testing is only performed at a few centers and is only available for a
limited number of disorders. Preimplantation testing is not possible in some cases due to difficulty in
obtaining eggs or early embryos and problems with DNA analysis procedures. Due to possible errors in
preimplantation diagnosis, traditional prenatal diagnostic methods are recommended to monitor these
pregnancies. The cost of preimplantation testing is very high and is usually not covered by insurance.
Newborn screening identifies individuals who have an increased chance of having a specific genetic
disorder so that treatment can be started as soon as possible.
Points to consider: Newborn screening programs are usually legally mandated and vary from state to
state. Newborn screening is performed routinely at birth, unless specifically refused by the parents in
writing. Screening tests are not designed to be diagnostic, but to identify individuals who may be
candidates for further diagnostic tests. Many parents do not realize that newborn screening has been
done (or which tests were included), even if they signed a consent form when their child was born.
Education is necessary with positive screening results in order to avoid misunderstandings, anxiety and
discrimination.
Reference:

GeneTests – Educational Materials - About Genetic Services (What is Genetic Testing?) (Uses of
Genetic testing): www.genetests.org
EMQN - European Molecular Genetics Quality Network
Documents, but no definitions found.
EuroGentest - Harmonizing Genetic Testing across Europe (Unit 3 2008) [18]
The recommendations apply to genetic counselling related to genetic testing, whereby the term genetic
test is used mainly for tests performed in genetic testing laboratories (cytogenetics, molecular genetics
and biochemical genetics) as part of genetic services. It is acknowledged that the same need for genetic
counselling may exist when analysing other elements that may disclose equivalent genetic information
(histological, imaging, family history, etc).
…
Different types of genetic testing situations and need for genetic counselling:
Depending on the context, the disease being tested and the implications for the individual and his or her
relatives, there may be different needs. It is assumed that clinical utility of the tests concerned is
adequate. This paper focuses on the average situations, but the authors realise that there may be
exceptions in each category.
Diagnostic testing means a genetic test performed in a symptomatic individual to confirm or exclude a
genetic condition. This is usually not very different from other medical tests performed in order to achieve
a diagnosis, except for the possible involvement of relatives or implications concerning them. Pre-test
genetic counselling may not always be necessary. As in case of any medical test, there should be free and
informed consent which includes pre-test information, minimally what the test is for and what its
implications are for the tested and for the family. If the test result is positive, the patient and the relatives
48
should be offered genetic counselling. Even when the test result is negative, genetic counselling may be
indicated.
Predictive testing refers to genetic testing in a healthy high-risk relative for a specific later-onset
monogenic disorder. The mutation in the family leads to the disease or a considerably high risk for the
disease (like in high risk familial cancers). There is not a complete consensus on the terminology: Some
use "presymptomatic testing" as a synonym for "predictive testing" - and even prefer this term - while
others restrict the terminology "presymptomatic testing" to mutations with full penetrance. Those in
favour of "predictive testing" use the term in the context of mutations with incomplete as well as
complete penetrance. Even if the family has previously been counselled, further pre- and post-test
genetic counselling has to be offered, often accompanied by psychosocial evaluation and support.
Susceptibility testing (sometimes referred to as risk profiling) means a genetic test of a marker or
simultaneous testing of several genetic markers with the aim to detect an increased or decreased risk for
a multifactorial condition in a healthy individual. The clinical validity and utility of risk profiling for
diseases of complex aetiology needs to be proven before clinical use. If the test is or is claimed to be
capable of detecting high relative risk for a serious condition and thus has significant implications for risk
assessment, treatment or prevention in a person or his/her near relatives, then pre- and post-test genetic
counselling is needed. At present, this is rarely the case in multifactorial diseases when testing healthy
individuals with non-specific family history.
Pharmacogenetic testing means testing for a genetic susceptibility for adverse drug reactions or for the
efficacy of a drug treatment in an individual with a given genotype. They are ordered mainly by specialists
other than clinical geneticists; and the need for proper genetic counselling by a genetic specialist will
depend on whether the results have other implications than the decisions about the drug treatment for
the person tested and his/her near relatives.
Carrier testing means a genetic test that detects a gene mutation that will generally have limited or no
consequence to the health of that individual. However, it may confer a high risk of disease in the
offspring, if inherited, from one parent (in case of X-linked inheritance, autosomal dominant premutation
or chromosomal translocation) or in combination with the same or another mutation in the same gene
from the other parent (in case of autosomal recessive inheritance). Pre- and post-test genetic counselling
needs to be offered.
Prenatal testing refers to a genetic test (either to detect a mutation, linked haplotype or chromosomal
change) performed during a pregnancy, where there is increased risk for a certain condition in the foetus.
Pre- and post-test genetic counselling for the prospective parents needs to be offered.
Preimplantation genetic diagnosis (PGD) means testing the presence of a mutation, linked haplotype or
chromosomal change in one or two cells of an embryo in a family with a previously known risk for a
Mendelian or chromosomal disorder, in order to select the unaffected embryos to be implanted. Pre- and
post-test genetic counselling for the prospective parents has to be offered. This should be differentiated
from preimplantation genetic screening (PGS), which aims at improved results of infertility treatment in
families with no known genetic risks. In case of PGS, reproductive counselling by assisted reproduction
professionals is usually appropriate.
Genetic screening means testing where the target is not high risk individuals or families, but where the
test is systematically offered to the general population or a part of it (e.g. newborns, young adults, an
ethnic group, etc.). All of the previously mentioned testing types can, in principle, be performed either in
families at risk or as screening programs in different parts of the population. In screening programmes,
pre-test information and post-test information has to be an integral part of the program, though the
extent and content of information in these lower risk situations, and the professionals involved, may vary.
In addition to this information, those who are found to be in a high-risk group, as a result of screening,
should be offered genetic counselling.
49
Reference:

Recommendations for genetic counselling related to genetic testing:
http://www.eurogentest.org/web/info/public/unit3/final_recommendations_genetic_counsel
ling.xhtml
EuroGentest - Harmonizing Genetic Testing across Europe (Patients leaflets 2007)
Genetic Testing
A genetic test can help identify if there is a change in a particular gene or chromosome. It is usually a
blood or tissue test. There are a number of reasons why a person might take a genetic test. Some of the
reasons are listed below:
 You or your partner have a child with learning difficulties, developmental delay or health problems.
The doctor thinks it might be a genetic condition.
 Your doctor thinks you may have a genetic condition and wants to confirm the diagnosis.
 There is a genetic condition that happens in your family. You want to know if you are at high risk of
developing the condition during your lifetime.
 You or your partner have a genetic condition that might be passed on to your children.
 You have had another type of test that is done during pregnancy (such as an ultrasound, nuchal
translucency scan or blood test). It has shown that there is an increased risk that your baby has a
genetic condition.
 You or your partner have had a miscarriage or stillbirth.
 Particular types of cancer have occurred in several close relatives.
 There is an increased risk of having a child with a particular genetic condition because of your ethnic
background. Examples of this include sickle cell in people of Afro- Caribbean descent, beta thalassaemia in people of Mediterranean descent, cystic fibrosis in people of Western European
descent and Tay Sachs in people of Ashkenazi Jewish descent. These conditions are more prevalent in
these particular ethnic groups, but may occur in others.
It will not always be necessary for the doctor or health professional to do a genetic test. They may be able
to diagnose a genetic condition through a clinical examination, or tell you about your risk by looking at a
detailed family history.
Reference:
 What is a Genetic Test? Information for Patients and Families:
www.eurogentest.org/blocks/leaflets/pdf/english/genetic_test.pdf
6. NATIONAL HEALTH INSTITUTIONS
Health Council, Netherlands (2006)
Pre-implantation genetic diagnosis (PGD) is the examination in vitro of an embryo (or an egg cell prior to
fertilisation) in order to exclude a genetic condition in case a very high risk of that condition is known.
PGD can only be used in combination with in vitro fertilisation (IVF).
50
Reference:

Pre-implantation Genetic Diagnosis, Health Council of the Netherlands (2006):
http://www.gr.nl/adviezen.php?ID=1333&highlight=genetic
Health Council, Netherlands (1999)
The regulations on clinical genetic testing and counselling in the Netherlands apply to "postnatal and
prenatal chromosome, biochemical and DNA testing, the clinical removal of foetal material, advanced
ultrasound scanning for foetal abnormalities and complex genetic counselling". The regulations are
designed to assure the quality and continuity of the procedures in question, which are regarded as a form
of medical care.
Experimental research has increased the potential applications of clinical genetic testing considerably. As
indicated in the Health Council's earlier advisory report "DNA Diagnostics", both the Human Genome
Project and research into specific hereditary conditions have yielded a great deal of clinically relevant
information. It should also be pointed out that diagnostic DNA tests, including tests for germline
mutations, are not carried out exclusively as a basis for genetic counselling. Furthermore, the results of
diagnostic biochemical tests are frequently not of a clinical genetic nature.
Reference:

Health Council of the Netherlands: Standing Committee on Genetics. Clinical genetic testing
and counselling. The Hague: Health Council of the Netherlands (1999); publication no.
1999/07), ISBN 90-5549-259-0: http://www.gezondheidsraad.nl/en/publications/clinicalgenetic-testing-and-counselling
Health Council, Netherlands (1994)
Prenatal testing - amniocentesis, chorionic-villus sampling (CVS), and tests on foetal blood from the
umbilical cord - can be used to determine the sex of a foetus, or to detect chromosomal abnormalities or
an increasing number of metabolic disorders (Royal College of Physicians. Prenatal diagnosis and genetic
screening. Report. Londen 1989). Germline-cell gene therapy involves the correction of one or more
genes in cells which form part of the germ line, that is, egg and sperm cells, and the totipotent cells of the
pre-embryo. Genetic counselling is a communication process which deals with the human problems
associated with the occurrence, or the risk of occurrence, of a genetic disorder in a family. This process
involves an attempt by one or more appropriately trained persons to help the individual or family to 1)
comprehend the medical facts, including the diagnosis, probable course of the disorder, and the available
management; 2) appreciate the way in which heredity contributes to the disorder, and the risk of
recurrence in specified relatives; 3) understand the alternatives for dealing with the risk of recurrence; 4)
choose the course of action which seems to them appropriate in view of their risk, their family goals, and
their ethical and religious standards, and to act in accordance with that decision and 5) make the best
possible adjustment to the disorder in the affected family member, and/or to the risk of recurrence of the
disorder. (Health Council Report: Gezondheidsraad. Ethiek van de erfelijkheidsadvisering. Den Haag 1980).
The main purpose of genetic counselling is to provide clients with the information they need to make the
choices appropriate to their beliefs and circumstances. Clients usually ask questions related to their
potential offspring; the information they receive covers a wide range. This may include the diagnosis of
the condition about which guidance is sought, the prognosis, the risk that a child - whether a first or
subsequent - will be handicapped, the treatment available for particular conditions, and the options open
to the client. The options generally are:
 to accept the risk (or perhaps certainty) that a child will be born with a handicap;
51
 to seek abortion, if prenatal testing reveals an abnormality;
 to opt for artificial procreation (insemination using donor sperm, or in vitro fertilization using a

donor egg) ;
to decide not to have (more) children, and perhaps to adopt.
Carriers - those not themselves affected but able to transmit the condition to their offspring
Genetic screening may involve chromosome testing, be carried out to determine the presence of
mutations directly, or it may involve biochemical examination of substances indicating the presence of a
mutation or a heightened risk of congenital abnormalities or hereditary disorders. In addition, ultrasound
scanning can be used at the prenatal stage to detect anatomical defects in the fetus.
The committee understands ‘genetic screening’ to mean any kind of test performed on people for the
systematic early detection or exclusion of a hereditary disease, the predisposition to such a disease or to
determine whether a person carries a predisposition which may produce a hereditary disease in their
offspring. In the following pages, the committee provides a further explanation of this definition, and of
the boundaries which were drawn during the preparation of this report.
The committee understands ‘early detection’ to mean: the search for disease, predisposition or carrier
status in those who have not (yet) been led to seek medical aid because of physical signs, symptoms or
anxiety. In the case of carriers, detection occurs at a time when there are still opportunities for genetic
counselling, or further tests, with regard to reproduction. In screening it is the care system which takes
the initiative with regard to detection. The committee understands ‘screening’ to mean determining in
advance those who are eligible for early detection (the target group) and approaching this group in a
systematic way. Here, ‘systematic’ is taken to mean that (in principle) every member of the target group is
specifically invited to take part in (or is expressly informed concerning the opportunities offered by) early
detection of the disease, predisposition or of carrier status.
The definition of genetic screening therefore has the following distinguishing characteristics:
 hereditary disease, predisposition or carrier status
 no reason for those involved to seek assistance
 systematic approach to the target group.
All of these characteristics must be present before the term genetic screening can be used. In the
committee’s view, characteristics such as the organisational form, the scale involved, the place where
early detection is actually carried out and the question whether it is a new or a previously accepted part
of the health service) are not of overriding importance for the definition. In any case, such characteristics
can vary from one screening programme to another. Therefore, screening need not take the form of large
scale population testing.
The committee acknowledges that even the definition selected here is still not totally sound. By way of
illustration: From the viewpoint of public health, a comprehensive publicity campaign which causes
virtually all members of the target group to request early detection has the same implications as issuing
individual invitations to the members of a target group. The character and the extent of such publicity
campaigns tend to obscure the distinction between individual requests and making an offer. The
committee sees the express provision of information as constituting an offer. Another point is that genetic
testing in relatives (necessary in order to respond to individual requests for genetic counselling) can also
be included within the definition. In the field of genetics, it would appear to be difficult to draw clear
borders between individual genetic testing, genetic testing within families, and genetic screening. These
show considerable similarities in terms of the desired effects (enabling people to make meaningful
choices), the possible risks and the conditions for good implementation and supervision. As a result,
within the framework of this report, the committee has opted for an overly broad interpretation of the
concept of genetic screening rather than an overly narrow one. This means that the committee has also
included in its deliberations the family testing as currently performed in clinical genetics centres.
However, this in no way implies that the committee feels that the status of such family testing should be
changed in any way whatsoever. It is simply that the committee views family testing from a different
52
perspective to that usually adopted by the medical profession. The profession sees family testing as
constituting individual medical aid, while it views screening as studies involving (large parts of) the
population. The committee considers that screening is not necessarily (by definition) a large scale activity
while family testing is not necessarily a small scale undertaking.
The committee will return later on (7.2) to the matter of the relationship between the concepts of
‘genetic screening’ and ‘population screening’ (within the context of the Population Screening Act) and to
the role played by family testing.
There is yet another reason for applying a broad interpretation of the concept of genetic screening.
Screening during the prenatal phase involves the use of ultrasonography, which also detects nonhereditary foetal defects. It is the committee’s view that the search for such defects (which is irrevocably
linked to this technique) also falls within the scope of this report.
The State Secretary also requested that consideration be given to testing for non-hereditary disorders.
The committee thinks that, from the viewpoint of the technology used, there is actually very little
difference between the early detection of hereditary diseases and of diseases lacking a hereditary
component. Exceptions to this are certain factors which play a part in infectious diseases. Thus, when
examining the question of genetic screening, problems could (in principle) be encountered which are
involved in other types of disorders. However, the objectives and the social implications of genetic
screening often extend much further, since such screening can also have repercussions for others (in this
instance for descendants or for other members of the family). This is something which genetic screening
has (to some extent) in common with the detection of infectious diseases such as tuberculosis or AIDS.
However, the committee has not studied the special aspects and specific implications associated with the
detection of infectious diseases. Since it considers the investigation of genetic screening to be a complex
matter in itself, the committee will restrict itself to this topic in the present report.
Reference:

Genetic Sreening – A Report of a Committee of the Health Council of the Netherlands (19 Dec
1994): www.gezondheidsraad.nl/pdf.php?ID=1221p=1
Health Council, Netherlands (1989)
4.1.1 Content and quality of genetic counselling
There is a number of different definitions for the term 'genetic counselling'. That which is now almost 67
universally accepted, and which is here endorsed, was formulated in an earlier Health Council report
(GR80): Genetic counselling is a communication process which deals with the human problems associated
with the occurrence, or the risk of occurrence, of a genetic disorder in a family.
This process involves an attempt by one or more appropriately trained persons to help the individual or
family to 1) comprehend the medical facts, including the diagnosis, probable course of the disorder, and
the available management; 2) appreciate the way in which heredity contributes to the disorder, and the
risk of recurrence in specified relatives; 3) understand the alternatives for dealing with the risk of
recurrence; 4) choose the course of action which seems to them appropriate in view of their risk, their
family goals, and their ethical and religious standards, and to act in accordance with that decision and 5)
make the best possible adjustment to the disorder in the affected family member, and/or to the risk of
recurrence of the disorder.
According to this definition, the purpose of genetic counselling is not to maintain or to improve general
standards of health, but to assist individuals who are seeking advice. This is a task for the counsellor. In
the following section, this task will be examined more closely, with respect to three aspects: information,
advice and support.
53
Reference:

Heredity: Science and Society - On the Possibilities and Limits of Genetic Testing and
Gene Therapy (HCN 1989), Report issued by a Committee of the Health Council of
The Netherlands, submitted to the Minister and State secretary of Health, Welfare
and Cultural Affairs, No 89/31, The Hague (29 Dec 1989):
http://www.gezondheidsraad.nl/sites/default/files/heredity.pdf
SACGHS - US Secretary's Advisory Committee on Genetics, Health, and Society, NIH
(2006) [19]
Scientific and technical advances have expanded our knowledge of genetic contributions to disease and
have made possible the development of genetic tests that are capable of diagnosing current disease,
assessing the risk of future disease and enabling treatment to be tailored to individual genetic variation.
Genetic/genomic tests and technologies - processes or methods used to analyse human DNA, RNA,
genes, chromosomes, proteins or metabolites that detect mutations, chromosomal changes, karyotypes,
phenotypes and/or expression pattern variation.
Genetic/genomic technologies are applied to tests for germline, inherited, and/or acquired variations in
the genome, transcriptone and proteome. Genetic tests generally focus on testing one or a few genes,
whereas genomic tests assess larger numbers of genes and sequences up to the context of the entire
genome. Throughout this report, use of the terms “genetic test”, “genetic technology”, or some variation
thereof implies inclusivity of all genetic and genomic technologies.
Historically, genetic tests have been used to identify germline or heritable variations in an individual’s
genome, whether analysing DNA, RNA or proteins. Currently, the term “genetic test” is used more broadly
to refer to any test performed using molecular biology methods to test DNA or RNA, including germline,
heritable, and acquired somatic variations. As we advance toward genomic medicine, with acquired
somatic variations evaluated in the context of an individual’s entire genome variations, the definition of a
genetic test will become even broader. Therefore although this report focuses on genetic tests and
services with a narrower definition, it is SACGHS’s intention that lessons learned from genetic tests and
services be applied to future innovation in clinical care developed using genetic/genomic technologies
involving germline inherited and acquired alterations. However, because tests for germline heritable
variations have more implications for all blood relatives of an individual patient compared with somatic
acquired variations, in some contexts, including but not limited to science policy, testing oversight, and
ethical contexts, the narrower definition of a genetic test as a test for a germline and/or heritable
alteration, and not for somatic variants, should be used.
Genetic/genomic tests can be used to diagnose a disease, predict future disease, predict risk or
susceptibility to disease, direct clinical management, identify carriers of genetic mutations and establish
prenatal or clinical diagnosis or prognosis in individuals, families or populations. Genetic/Genomic tests
may be used, for example, in preimplantation diagnosis and newborn screening.
Predictive testing determines the probability that a healthy individual might develop a certain disease in
the future.
Pharmacogenetic/pharmacogenomic tests are used to determine the likelihood of a person being
responsive to a particular drug and/or having an adverse event.
(Genetic/genomic technologies used for nonmedical purposes such as forensic identification or
establishing paternity or familial relationships are not considered in this report)
54
Reference:

Coverage and Reimbursement of Genetic Tests and Services – Report of the Secretary’s
Advisory Committee on Genetics, Health and Society, SACGHS, US Department of Health and
Human Services (Feb 2006): http://www4.od.nih.gov/oba/sacghs/reports/CR_report.pdf
SACGT - US Secretary's Advisory Committee on Genetic Testing, NIH (2000)
(also NHGRI task force; same as NIH-DOE-ELSI report) [20]
A genetic test is an analysis performed on human DNA, RNA, genes and/or chromosomes to detect
heritable or acquired genotypes, mutations, phenotypes, or karyotypes that cause or are likely to cause a
specific disease or condition.
A genetic test also is the analysis of human proteins and certain metabolites, which are predominantly
used to detect heritable for acquired genotypes, mutations or phenotypes. The purposes of these genetic
tests include predicting risks of disease, screening of newborns, directing clinical management, identifying
carriers, and establishing prenatal or clinical diagnoses or prognoses in individuals, families or
populations. Tests that are used primarily for other purposes, but that may contribute to diagnosing a
genetic disease (e.g. blood smear, certain serum chemistries), would not be covered by this definition.
Also excluded from the definition are tests conducted exclusively for forensic identify purposes.
Genetic tests can be performed for a number of purposes. Moreover, a test can be used in more than one
way, such as when a test used for diagnostic purposes is also used to predict risk of disease.
Preimplantation diagnosis is used following in vitro fertilization to diagnose a genetic disease or condition
in a preimplantation embryo.
Prenatal diagnosis is used to diagnose a genetic disease or condition in a developing fetus.
Newborn screening is performed in newborns in state public health programs to detect certain genetic
diseases for which early diagnosis and treatment are available.
Carrier testing is performed to determine whether an individual carries one copy of an altered gene for a
particular recessive disease. Recessive diseases occur only if both copies of a gene that an individual
receives have a disease-associated mutation; thus, each child born to two carriers of a mutation in the
same gene has a 25-percent risk of being affected with the disorder.
Diagnostic/confirmatory testing is used to identify or confirm the diagnosis of a disease or condition in an
affected individual. Diagnostic testing may also be useful to help determine the course of a disease and
choice of treatment.
Predictive testing determines the probability that a healthy individual with or without a family history of a
certain disease might develop that disease.
Presymptomatic testing refers to predictive testing of individuals with a family history. Historically, the
term presymptomatic testing has been used when testing for diseases or conditions such as Huntington
disease where the likelihood of developing the condition (known as penetrance) is very high in people
with a positive test result.
Reference:

Enhancing the oversight of genetic tests: Recommendations of the SACGT, Secretary's Advisory
Committee on Genetic Testing (Jun 2000):
http://www4.od.nih.gov/oba/sacgt/gtdocuments.html
55
NHGRI - National Human Genome Research Institute (2005) [21]
Genetic test -The analysis of human DNA, RNA, chromosomes, proteins, and certain metabolites in order
to detect heritable disease-related genotypes, mutations, phenotypes or karyotypes for clinical purposes.
Such purposes include predicting risk of disease, identifying carriers and establishing prenatal and clinical
diagnosis or prognosis. Prenatal, newborn and carrier screening, as well as testing in high-risk families, are
included. Tests for metabolites are covered only when they are undertaken with high probability that an
excess or deficiency of the metabolite indicates the presence of heritable mutations in single genes. Tests
conducted purely for research are excluded from the definition, as are tests for somatic (as opposed to
heritable) mutations, and testing for forensic purposes.
Reference:

Promoting Safe and Effective Genetic Testing in the United States (2005):
http://www.genome.gov/10002405
NCI - National Cancer Institute, NIH, US
Genetic Testing - Analyzing DNA to look for a genetic alteration that may indicate an increased risk for
developing a specific disease or disorder.
Genetic Analysis - The study of a sample of DNA to look for mutations (changes) that may increase risk of
disease or affect the way a person responds to treatment.
Genetic Counseling - A communication process between a specially trained health professional and a
person concerned about the genetic risk of disease. The person's family and personal medical history may
be discussed, and counseling may lead to genetic testing.
Genetic Marker - Alteration in DNA that may indicate an increased risk of developing a specific disease or
disorder
Genetic Susceptibility - An inherited increase in the risk of developing a disease.
Reference:

Dictionary of Cancer Terms: http://www.cancer.gov/dictionary
7. Health Professionals Organizations
WMA - World Medical Association (2005; amended 2009)
Genetic Testing
The identification of disease-related genes has led to an increase in the number of available genetic tests
that detect disease or an individual's risk of disease. As the number and types of such tests and the
diseases they detect increases, there is concern about the reliability and limitations of such tests, as well
as the implications of testing and disclosure. The ability of physicians to interpret test results and counsel
their patients has also been challenged by the proliferation of knowledge.
Genetic testing may be undergone prior to marriage or childbearing to detect the presence of carrier
genes that might affect the health of future offspring. Physicians should actively inform those from
populations with high incidence of certain genetic diseases about the possibility of pre-marital and pre-
56
pregnancy testing, and genetic counselling should be made available to those individuals or couples who
are considering such testing.
Genetic counselling and testing during pregnancy should be offered as an option. In cases where no
medical intervention is possible following diagnosis, this should be explained to the couple prior to their
decision to test.
In recent years, with the advent of IVF, genetic testing has been extended to pre-implantation genetic
diagnosis of embryos (PGD). This can be a useful tool in cases where a couple has a high chance of
conceiving a child with genetic disease.
Since the purpose of medicine is to treat, in cases where no sickness or disability is involved, genetic
screening should not be employed as a means of producing children with pre-determined characteristics.
For example, genetic screening should not be used to enable sex selection unless there is a gender-based
illness involved. Similarly, physicians should not countenance the use of such screening to promote nonhealth related personal attributes.
Genetic testing should be done only with informed consent of the individual or his/her legal guardian.
Genetic testing for predisposition to disease should be performed only on consenting adults, unless there
is treatment available for the condition and the test results would facilitate earlier instigation of this
treatment.
Valid consent to genetic testing should include the following factors:
The limitations of genetic testing, including the fact that the presence of a specific gene may denote
predisposition to disease rather than the disease itself and does not definitively predict the likelihood of
developing a certain disease, particularly in multi-factorial disorders.
The fact that a disease may manifest itself in one of several forms and in varying degrees.- Information
about the nature and predictability of information received from the tests.
The benefits of testing including the relief of uncertainty and the ability to make informed choices,
including the possible need to increase or reduce regular screenings and checkups and to implement risk
reduction measures.
The implications of a positive result and the prevention, screening and/or treatment possibilities.
The possible implications for the family members of the patient involved.
In the case of a positive test result that may have implications for third parties such as close relatives, the
individual tested should be encouraged to discuss the results of the test with such third parties. In cases
where not disclosing the results involves a direct and imminent threat to the life or health of an individual,
the physician may reveal the results to such third parties, but should usually discuss this with the patient
first. If the physician has access to an ethics committee, it is preferable to consult such a committee prior
to revealing results to third parties.
Genetic Counselling
Genetic counselling is generally offered prior to marriage or conception, in order to predict the likelihood
of conceiving an affected child, during pregnancy, in order to determine the condition of the fetus, or to
an adult, in order to determine susceptibility to a certain disease.
Individuals at higher risk for conceiving a child with a specific disease should be offered genetic
counselling prior to conception or during pregnancy. In addition, adults at higher risk for various diseases
such as cancer, mental illness or neuro-degenerative diseases in which the risk can be tested for, should
be made aware of the availability of genetic counselling.
Because of the scientific complexity involved in genetic testing as well as the practical and emotional
implications of the results, the WMA sees great importance in educating and training medical students
and physicians in genetic counselling, particularly counselling related to pre-symptomatic diagnosis of
57
disease. Independent genetic counsellors also have an important role to play. The WMA acknowledges
that there can be very complex situations requiring the involvement of medical genetics specialists.
In all cases where genetic counselling is offered, it should be non-directive and protect the individual's
right not to be tested.
In cases of counselling prior to or during pregnancy, the prospective parents should be given information
to provide the basis for an informed decision regarding childbearing, but should not be influenced by the
physicians' personal views in this matter and physicians should be careful not to substitute their own
moral judgment for that of the prospective parents. In cases where a physician is morally opposed to
contraception or abortion, he/she may choose not to provide these services but should alert prospective
parents that a potential genetic problem exists and make note of the option of contraception or abortion
as well as treatment alternatives, relevant genetic tests, and the availability of genetic counselling.
Reference:

WMA Statement on Genetics and Medicine. Adopted by the 56th WMA General Assembly,
Santiago, Chile (Oct 2005); and amended by the 60th WMA General Assembly, New Delhi, India
(Oct 2009): http://www.wma.net/en/30publications/10policies/g11/
FIGO - International Federation of Gynecology and Obstetrics
Documents, but no definitions found.
ISONG - International Society of Nurses in Genetics (2005)
Genetic information refers to any information about a person that identifies inherited traits or
characteristics, or genetic alterations that are acquired during a person's lifetime.
Reference:

Privacy and confidentiality of Genetic Info: the role of nurses, ISONG (2005):
http://www.isong.org/about/ps_privacy.cfm
RCP - Royal College of Physicians, Royal College of Pathologists and British Society for
Human Genetics (Joint Committee on Genetic Testing 2011)
Historically, genetic tests in the UK have been performed largely by regional genetic services – a series of
NHS-funded clinics to which individuals or families can be referred. The genetics professional usually
starts by taking a detailed family history, identifying details about the relationship and health of members
of three or four generations in that family. This allows conclusions to be drawn about likely inheritance
patterns and may help direct genetic testing. It will also identify named individuals who might benefit
from the information gleaned through this process. Rather than holding individual records, genetic
services often hold family records which group all the relevant genetic information into one set of case
notes. Over recent years, genetic technologies have become faster and cheaper, and the evidence basis
for diagnostic or predictive information arising from such tests, greater.
Genetic testing is now being integrated rapidly into mainstream medical specialties. The issues
surrounding consent, confidentiality and sharing of genetic information are therefore now pertinent to
most branches of medicine. See Box 1 for some practical aspects of clinical genetic practice.
58
Whilst genetic information is relevant to an individual, as noted, it may also be relevant to that person’s
family because much genetic information will be common to both. Indeed, genetic testing may only be
requested because of wider knowledge about a condition within a family. The traditional medical
approach which focuses on the individual patient to the exclusion of others may be difficult to apply to
the use of genetic information. For example, testing one person can reveal information about the chances
of a condition occurring in their close relatives and providing the tested person with a right of veto over
such risk information in all situations may be legally and ethically unsound. At the same time, respecting
confidential information is an important aspect of clinical practice and is vital in securing public trust and
confidence in healthcare.
Once a genetic diagnosis has been made, health professionals will usually ask an individual to share their
genetic results with the relatives to whom it may be relevant. Discussion of the family history and the
pattern of inheritance will facilitate identification of those to whom such information might be relevant.
Clinical genetic services often offer help with this process of cascading information, and may provide
letters or information leaflets to be passed on. There is considerable variation in practice in such
communication, and the degree to which patients directly contact their relatives. Some research suggests
that direct contact of relatives by professionals is more effective in identifying those at risk than awaiting
intrafamilial communication whilst others are concerned about invading the privacy of relatives who have
not asked for contact. Notwithstanding ethical objections, there are significant practical hurdles in
contacting a range of relatives who may be difficult to identify and locate. For these reasons, current UK
genetic practice largely leaves the onus of communication with the individual first diagnosed. Such
communication may take place effectively but at times, perhaps where family members are not in close
contact, or because of concerns to protect people from distressing information, or through fear of blame
or stigmatisation, relatives may remain in ignorance. Health professionals may not know whether
information has been passed on and may meet individuals from a family to whom they could provide
more accurate information, but concern about breaching the confidentiality of another prevents them
from doing so.
The distinction between diagnostic and predictive genetic testing: although some tests will have both
diagnostic and predictive elements, there are different implications for understanding and management
of genetic conditions depending on whether a test is diagnostic or predictive of ill health in the future,
and these differences may need highlighting to other health professionals involved in a patient’s care.
Reference:

Royal College of Physicians, Royal College of Pathologists and British Society for Human
Genetics. Consent and confidentiality in clinical genetic practice: guidance on genetic testing
and sharing genetic information. Report of the Joint Committee on Medical Genetics. RCP,
RCPath (2011): http://www.geneticseducation.nhs.uk/media/47812/report.pdf
BMA - British Medical Association (Board of Science 2005)
Screening is a public health service in which members of a defined population, who do not necessarily
perceive that they are at risk of, or are already affected by, a disease or its complications, are questioned
or offered a test. The aim is to identify those individuals who are more likely to be helped than harmed by
further tests or treatment to reduce the risk of a disease or its complications. (UK National Screening
Committee at www.nsc.nhs.uk - go there now - accessed September 2004).
A distinction needs to be made between genetic screening and genetic testing.
Screening involves testing members of a population for a disorder for which there is no prior evidence of
the condition, although they may be part of a higher risk group, such as Ashkenazi Jews who are at risk of
developing Tay Sachs disease (National Institute of Neurological Disorders and Stroke, www.ninds.nih.gov
- accessed January 2005).
59
Testing relates to those who know that they are at risk, such as people belonging to families that may
carry high penetrance genes associated with breast cancer, or with a history of Huntington’s disease
(National Institute of Neurological Disorders and Stroke, www.ninds.nih.gov). Genetic testing can mean
carrying out a genetic test for a condition, such as Alzheimer’s (National Institute of Neurological
Disorders and Stroke, www.ninds.nih.gov) and coronary heart disease (Diabetes, heart disease and stroke
(DHDS) prevention pilot project, www.nelh.nhs.uk/screening). It can also be testing for a genetic disease,
which may or may not involve identifying the genetic makeup. Examples include cystic fibrosis (Cystic
Fibrosis Trust, www.cftrust.org.uk) and sickle cell disease. (Sickle Cell Society, www.sicklecellsociety.org).
Genetic screening raises specific concerns where a hereditary condition is being tested for, as it will have
implications not only for the individual, but also for family members.
Predisposition testing may show lower levels of risk. While this does not resolve issues of uncertainty
about developing the disease, it may be useful where changes can be made to reduce the chance of
developing the disease, for example lifestyle changes relating to heart disease.
Presymptomatic genetic testing, which establishes whether a disorder will develop, raises few concerns
where effective medical intervention is available.
Genetic testing may identify people as carriers of a genetic mutation, and while not actually suffering
from the disease themselves, the discovery would have implications for their children, siblings and
relatives of childbearing age.
Preimplantation genetic diagnosis (PGD) is ‘a technique which involves the genetic testing of embryos
created in vitro for deleterious heritable genetic conditions which are known to be present in the family of
those seeking treatment and from which the embryos are known to be at risk’ (Human Fertilisation and
Embryology Authority, www.hfea.gov.uk - accessed December 2004)
Pharmacogenetics is the study of how a response to a drug is influenced by genetic makeup (Royal
Society, www.royalsoc.ac.uk (accessed January 2005), Wolf C R, Smith G & Smith R L (2000) Science,
medicine and the future: Pharmacogenetics. BMJ 320: 987-90).
Reference:

Population screening and genetic testing (Aug 2005):
http://www.bma.org.uk/ap.nsf/AttachmentsByTitle/PDFscreeningbriefingsecond/$FILE/Screenin
gBriefing2.pdf
AMA - American Medical Association (2005)
Genetic testing usually refers to the analysis of DNA to identify changes in gene sequence (deletions,
additions, or misspellings) or expression levels. Genetic testing can also refer to biochemical tests for gene
products (proteins) and for microscopic analysis of stained chromosomes. Genetics testing still is in its
early stages, so both patients and experienced physicians may need guidance when it comes to navigating
this new and emotionally complex territory.
How is genetic testing used clinically?
 Diagnostic medicine: identify whether an individual has a certain genetic disease. This type of test
commonly detects a specific gene alteration but is often not able to determine disease severity or
age of onset. It is estimated that there are >4000 diseases caused by a mutation in a single gene.
 Predictive medicine: determine whether an individual has an increased risk for a particular
disease. Results from this type of test are usually expressed in terms of probability and are
therefore less definitive since disease susceptibility may also be influenced by other genetic and
nongenetic (e.g. environmental, lifestyle) factors.
60
 Pharmacogenomics: classify subtle variations in an individual's genetic makeup to maximize a
drug's effectiveness and safety.
Genetic testing is performed for the following reasons:
 conformational diagnosis of a symptomatic individual
 presymptomatic testing for estimating risk developing disease
 presymptomatic testing for predicting disease
 prenatal diagnostic screening
 newborn screening
 preimplantation genetic diagnosis
 carrier screening
 forensic testing
 paternal testing
Gene testing involves examining a person’s DNA for some anomaly that could cause or increase the risk
for a disease or disorder. The DNA usually is taken from cells in a sample of blood or occasionally from
other body fluids or tissues. In addition to studying chromosomes or genes, genetic testing in a broader
sense can also include biochemical tests for the presence or absence of key proteins that signal aberrant
genes.
Pharmacogenomics is the study of how genes affect the way individuals respond to drugs. In this report,
the term pharmacogenomics refers to products that use any variety of biomarkers for diagnosis, drug
prescription, or patient treatment. These biomarkers can include differences in the DNA, RNA, alleles, and
single nucleotide polymorphisms (SNPs) among patients. This definition also includes all technologies that
involve gene therapy, gene expression, proteomics and bioinformatics.
References:


Genetic Testing (updated Jul 2005): http://www.ama-assn.org/ama/pub/category/9178.html
Basic Genetics (updated Jun 2005): http://www.ama-assn.org/ama/pub/category/4646.html
ICMR - Indian Council Medical Research (2000)
Somatic cell gene therapy is the only method that may be permissible for the purpose of preventing or
treating a serious disease when it is the only therapeutic option. It should be restricted to alleviation of
life threatening or seriously disabling genetic disease in individual patients and should not be permitted to
change normal human traits. However, rapid advance in science necessitates periodic review of guidelines
in this area. This includes evaluation of safety and efficacy of DNA vaccines and transgenic foods as well
Reference:

Ethical Guidelines for Biomedical Research on Human Subjects (2000):
http://www.icmr.nic.in/ethical.pdf
61
8. Clinical Pathologists Organizations
Royal College of Pathologists, UK (Joint Committee on Genetic Testing 2011)
See RCP - Royal College of Physicians, Royal College of Pathologists and British Society for Human
Genetics (Joint Committee on Genetic Testing 2011)
CAP - College of American Pathologists (2000) [22]
Definition of Genetic Testing:
CAP has defined genetic tests as those which provide information used for diagnosing or predicting an
inherited condition or carrier trait. The term “genetic tests” would properly include those used to detect
an inherited susceptibility or resistance to a disease. CAP believes that a narrow definition is necessary to
target exactly those tests which will generate information that is important enough clinically to warrant
counseling patients and their family members as to the risks of diseases. SACGT’s preliminary report
appears to define genetic tests as those which involve the analysis of chromosomes, DNA, RNA, genes,
and/or gene products to determine whether an alteration is present that is causing or is likely to cause a
specific disease (page 1). CAP believes this definition to be inappropriately broad and urges SACGT to take
a leadership role on determining genetic testing in a medically precise and approprite manner.
CAP cautions that an overly broad definition for genetic tests will inadvertently encompass the majority of
laboratory tests and thereby over-regulate even the simplest tests. This will add to costs but not enhance
quality. CAP understands how and why the term “genetic test” is often improperly defined. Virtually all
diseases have a genetic component, but not necessarily a classically inherited one. CAP restricts the term
“genetic tests” to those that detect classic hereditary disorders that are inherited when a mutation in
DNA is transmitted from one generation to another; for example, inheritance of a mutation in the BRCA-1
gene conferring predisposition to breast and ovarian cancer. We would exclude tests, even those that are
DNA-based, which target acquired or somatic mutations. These somatic gene mutations are far more
common than classic genetic disorders and are not heritable or transmitted to offspring.
CAP believes it is incumbent upon the SACGT to recognize the difference between germline and somatic
disorders and the tests that diagnose them. A definition that is too broad will encompass most laboratory
tests, such as routine cholesterol or glucose measurements, basic blood counts, as well as many DNA
based tests for noninheritable abnormalities, such as the bcr-abl translocation (Philadelphia chromosome)
in chronic myelogenous leukemia. Surely these tests have markedly different implications and concerns
from predictive genetic tests. An overly broad definition will defeat the mission of the SACGT to
specifically advise the Secretary of Health and Human Services about a subset of clinical laboratory tests
and would result in over-regulation and increased costs for tests which do not raise unique issues or
concerns.
Reference:

Paul Bachner, FCAP President: Public Comments on Preliminary Conclusions and
Recommendations on Oversight, p.28 (24 May 2000):
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2F
contentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}
=advocacy%2Fcomments%2Fgencomm.html&_state=maximized&_pageLabel=cntvwr
62
CAP - College of American Pathologists (2004) [22]
The College of American Pathologists has defined genetic tests as those that are used to detect an
inherited condition and that generate information that warrants counseling of patients and their family
members. Excluded from this definition are those tests that detect genetic abnormalities that represent
acquired or somatic mutations, such as with most cancers. It is worrisome that a broad interpretation of
Section 79-I could include tests for acquired mutations (e.g. Her 2/neu) under the ambiguous definition of
a genetic test as testing for a “genetic variation linked to a...disability in the individual...”
Reference:

Quality Assurance Standards for Genetic Testing (8 Mar 2004):
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2F
contentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentRefere
nce%7D=statline%2Fgenetic_tests.html&_state=maximized&_pageLabel=cntvwr~
AMP, Association for Molecular Pathology (2005) [23]
AMP continues to support the limitation in the definition of a genetic test to inheritable germline
variations, and not including somatic variations. If a genetic test is more broadly defined as any molecular
biology-based test, then there needs to be a distinction that allows for the discussion of the ethical, social,
and regulatory issues specific to inheritable genetic tests, separate from testing for somatic mutations, or
DNA and RNA-based infectious disease testing, which do not carry the same ethical and social concerns.
We realize that this distinction may not be relevant to the Coverage and Reimbursement Report, but it
may be relevant to future reports of the SACGHS.
One specific concern is the inclusion of pharmacogenetics testing in this discussion, since this testing
identifies allelic variants that are not associated with disease, but only affect drug metabolism. Only in the
presence of an external challenge (drug) will health risks be apparent
References:


Public Comment from the Association for Molecular Pathology presented by Mary Steele
Williams, AMP comments on Proposed Best Practices for the Licensing of Genomic Inventions,
Secretary’s Advisory Committee on Genetics, Health and Society (1 Mar 2005):
http://72.14.221.104/search?q=cache:7MD0H4dAGHwJ:www.amp.org/SACGHS/SACGHS030105.doc+Public+Comment+from+the+Association+for+Molecular+Pathology+presented+by
+Mary+Steele+Williams&hl=en&gl=uk&ct=clnk&cd=1
Comments on the Draft Coverage and Reimbursement, Mark A. Lovell, President, Association
for Molecular Pathology (6 May 2005): http://amp.org/SACGHS/AMPComments.doc
9. RESEARCH FUNDING AGENCIES
Welcome Trust
Documents, but no definitions found.
63
MRC - Medical Research Council, UK (2004)
Pre-implantation genetic diagnosis - A screening procedure in which a recognised practitioner removes
one or two cells from an embryo to test for specific genetic disorders/characteristics before proceeding
with embryo transfer.
Reference:

Assisted Reproduction – a safe and sound future (2004): http://www.mrc.ac.uk/prn/pdfassisted_reproduction.pdf
10. Industry
EuropaBio - European Association for Bioindustries (2004) [24]
Within this document we define human medical genetic testing as the use of a DNA sequence or
structure, in direct DNA-based tests or in any other test that provides DNA-specific health information
(including cytogenetic and biochemical tests).
Genetic testing by strict definition is any test that yields information about inherited characteristics based
on the analysis in vitro, (in a laboratory, i.e. outside the human body), of structural properties of DNA, or
of RNA, or proteins or other substances (which are a direct consequence of the underlying DNA
structure). The broader use of the term, genetic testing, also includes testing of structural properties of
DNA or RNA in specific cells, tissues or organs which are acquired during an individuals lifetime, e.g. in
certain forms of cancer. The broader use of the term genetic testing is used in this paper.
Medical genetic testing is the application of genetic testing to derive information relevant to health care,
as it relates to disease risk prediction, disease diagnosis, disease treatment, and reproductive health.
Non-medical genetic testing comprises the application of genetic testing for all purposes that do not
involve a medical decision, mainly for the purpose of identification, e.g. paternity and forensic testing,
and identification of the presence of animal and plant materials in foods or other materials
Reference:

Human Medical Genetic Testing. A EuropaBio Position Paper, The European Association for
BioIndustries (May 2004): http://www.europabio.org/articles/article_317_EN.doc
ABPI - Association of the British Pharmaceutical Industry (2002)
Pharmacodynamics The study of the effects of the drug on the body and the echanisms by which it acts
(what the drug does to the patient).
Pharmacogenetics The branch of biology that looks at how an individual’s genes affect the way that they
react to a particular drug.
Genetic Testing - To detect the presence or absence of, or alteration in, a particular gene, chromosome or
a gene product, in relation to a genetic disorder.
64
NOTE: ACGT’s definition of a genetic test is not restricted to a DNA or chromosome test. Many ‘biochemical’ tests will indicate that a person is likely to have a genetic or familial disorder and these should be treated by RECs as ‘genetic tests’.
(a) Diagnostic Genetic Testing – Use of genetic testing in a symptomatic individual to aid in their
diagnosis, treatment and management.
(b) Presymptomatic Genetic Testing – primarily carried out in healthy or asymptomatic individuals to
provide information about that individual's future health, with respect to specific inherited diseases. Such
a test result may indicate that the individual has a high likelihood of developing the disorder or of
excluding it.
Presymptomatic testing is most frequently used in late onset autosomal dominant disorders such as
Huntington’s Disease.
(c) Susceptibility Testing – which provides information about the genetic component in a multifactorial
disorder.
(d) Carrier Testing – used to detect individuals who possess a single copy of a gene which follows an
autosomal recessive pattern of inheritance (see below). Such an individual will not normally develop any
disease or disorder but may pass on the gene to his or her offspring.
References:


Introduction to the Work of Research Ethics Committees – What Is Involved in Being on a
Research Ethics Committee Considering Human Pharmacology:
http://www.abpi.org.uk/publications/pdfs/ethics_web.pdf
Personalized Medicine – The Emerging Pharmacogenomics Revolution:
http://www.pwc.com/techforecast/pdfs/pharmaco-wb-x.pdf
Glaxo, Smith and Kline
Documents, but no definitions found.
Novartis
No documents relating to genetic testing were found.
Roche (2005) [25]
Genetic testing can refer to several different things. In general, genetic testing is used to learn about
human genes. In some cases, we can analyze the parts of a person’s genome that relate to their health or
the health of their children. Patients need to be aware that genetic testing does have limits. Some
mutations may not be identified by tests at present, and for many diseases, genes are only one risk factor
and therefore may not tell the whole story.
Genetic testing can also refer to tests on the DNA of infectious agents. These agents may be found in
humans or in the environment. The hepatitis B virus is an example of an infectious agent.
Finally, genetic testing also refers to using DNA to identify someone. Examples are tests for paternity
(fatherhood) and for matching blood and hair found at a crime scene.
65
Pharmacogenetics is the study of the genetic basis for differences between people in the way they
respond to drugs. This information may help in drug research and development. It may also be helpful in
prescribing effective drugs in the right amounts to various patients.
Pharmacogenomics is the study of how all of a person’s genes (their genome) may affect how they
respond to certain drugs.
What are the medical uses of genetic tests?
Medical uses of genetic tests include finding inherited diseases, such as Huntington’s disease and sickle cell
anemia. People who have the genes for these disorders have a high risk of getting the disease. Therefore,
tests may also be used as possible preventative measures for persons at risk.
Tests for some disorders are done when the mother is pregnant or soon after the baby is born. These
include Fragile X Syndrome and Down syndrome. (Both these genetic disorders can cause mental
retardation.) Genetic testing is also used to advise prospective parents of the risk of having a baby with an
inherited disease, such as cystic fibrosis. This type of testing is called carrier testing.
Newborns are also routinely screened for some inherited disorders that may keep them from using certain
nutrients. These disorders can lead to severe disabilities if they aren’t treated soon after birth. Examples of
these disorders include phenylketonuria (PKU), hyperthyroidism and biotinidase deficiency.
Another example is a disorder that causes iron to build up in the body. It is called familial
hemochromatosis. Iron build-up can be fatal. Members of families with a history of this disorder can now
be tested for the genetic defect. If it is present, they can be followed closely to see if they develop the
disease (not all do). If they do get symptoms, they can be treated.
In the future, genetic testing may be used even more to guide doctors and patients in designing the best
treatments for each person enabling early treatment and prevention. For example, research is already
underway to better understand how genes affect the way a person responds to medications.
What are the non-medical uses of genetic tests?
Genetic tests are commonly used to determine the identity of a person. They are used to identify accident
victims. Police use them to test whether tissue (such as blood or hair) left at a crime scene matches up with
the suspect’s DNA. Genetic tests can also be used to determine paternity and other family relationships.
These tests don’t tell any other medical information about the person, though.
What is the impact of genetic testing within Roche?
Genetic testing is done in a laboratory, using cells gathered from inside the cheek or a blood sample. This
is called diagnostic or molecular testing.
Genetic testing is also used to advise prospective parents of the risk of having a baby with an inherited
disease, such as cystic fibrosis. This type of testing is called carrier testing.
Reference:

Genetic Testing in Research & Healthcare, Roche: http://www.roche.com/scigenetictesting.pdf
Genzyme (2010)
Genetic Counselor: A health care professional trained in the field of genetics who reviews a person's
family and medical history and determines the risks for possible diseases or conditions. Genetic
counselors explain the benefits, risks and limitations of testing options and procedures and facilitate
patient decision making regarding these options.
66
Reference:

Genzyme Glossary of terms:
http://www.genzymegenetics.com/hcp/prenatal/resources/gene_p_hcp_pre_resources_glos.
asp
11. Insurance Organizations
NAHU - National Association of Health Underwriters (2003)
NAHU's Position: NAHU supports the prohibition of the use of genetic information in the health insurance
underwriting process, provided that the definition of genetic information is limited to DNA, RNA and
related gene testing. Our position statement explains our views in greater detail, but in general we feel
that expanding the definition of genetic information to include an individual's personal and family medical
history will interfere with normal individual health insurance policy underwriting process. We are
concerned that the result of such interference will be higher premiums for the consumer and a greater
number of uninsured people.
NAHU supports a definition of genetic information that is limited to DNA and related gene testing done
for the purpose of predicting risk of disease in asymptomatic or undiagnosed individuals, and which
clearly excludes such items as age, gender, and information from physical exams and lab work including
items like cholesterol tests, performed to detect symptoms, clinical signs, or a diagnosis of disease.
References:


Genetic Discrimination: http://www.nahu.org/legislative/genetic/index.cfm
Position on Genetic testing (2003): http://www.nahu.org/legislative/Genetic_position.pdf
12. Patient/Consumers Organizations
DPI - Disabled Peoples International (2000)
Gene Therapy
Gene therapy involves making changes to the gene in order to treat a condition.
This could be done by adding a working copy of the faulty gene, by developing genetic-based drug therapy
or, as has already been unsuccessfully tried, by imparting a virus into the faulty gene.
There are two kinds of gene therapy:
 Somatic gene therapy - alters the individual gene level.
 Germ line therapy (or human genetic engineering) – alters all the cells in the b o d y, including the
reproductive cells and therefore can be passed on through reproduction. This therapy is prohibited
in most countries at the moment.
67
Reference:

Disabled People Speak on the New Genetics, DPI Europe Position Statement On Bioethics And
Human Rights (Nov 2000): http://freespace.virgin.net/dpi.europe/downloads/bioethicsenglish.pdf
EPPOSI - European Platform for Patient Organisations, Science and Industry
Documents, but no definitions found.
EURORDIS - European Organisation for Rare
Documents, but no definitions found.
Genetic Alliance (1997/2000) [26]
Carrier testing - The goal of these tests is identifying individuals, or couples, who carry a particular
recessive gene allele that would result in a particular genetic condition if a child were to inherit copies of
this allele from both parents. "Carrier testing is designed for healthy people who have no symptoms of
disease, but who are known to be at high risk of being a carrier for the disorder" (NCI, 1995, p.25)
Genetic testing - examining a sample of blood or other bodily fluid or tissue for biochemical,
chromosomal, or genetic markers that indicate the presence or absence of genetic mutations or genetic
conditions, including evidence of carrier status or a predisposition to developing a condition which has
multifactorial components.
Gene therapy - this refers to a medical procedure that treats a disorder by replacing the faulty gene.
PGD (Pre-implantion Genetic Diagnosis) - this is the testing of a fertilized egg for genetic disorders after invitro fertilization, before placing the embryo in the uterus for development.
Predictive gene tests - tests to identify gene mutations that may make a person susceptible to certain
diseases or disorders.
Prenatal diagnosis - examining fetal cells taken from the amniotic fluid, the primitive placenta (chorion),
or the umbilical cord for biochemical, chromosomal, or gene alterations.
Carrier - an individual who possesses one copy of a mutant allele that causes disease only when two
copies are present. Although carriers not affected by the disease, two carriers can produce a child who
has the disease. (National Human Genome Research Institute, National Institutes of Health (2000)
"Glossary of Genetic Terms")
Pharmacogenetics - The study of how people respond differently to medicines due to their genetic
inheritance. The term has been pieced together from the words pharmacology (the study of how drugs
work in the body) and genetics (the study of how traits are inherited). An ultimate goal of
pharmacogenetics is to understand how someone's genetic make-up determines how well a medicine
works in his or her body, as well as what side effects are likely to occur. In the future, advances gleaned
from pharmacogenetics research will provide information to guide doctors in getting just enough of the
right medicine to a person--the practice of "personalized medicine." (National Institute of General
Medical Sciences. National Institutes of Health (2000) "What is Pharmacogenetics?" Information)
Gene Therapy - the introduction of a normal, functioning gene into a cell in which that gene is missing or
defective.(National Institute of General Medical Sciences. National Institutes of Health (1993) "Medicines
by Design: The Biological Revolution in Pharmacology" NIH Publication No. 93-474.)
68
Genetic Counseling - a short-term educational counseling process for individuals and families who have a
genetic disease or who are at risk for such a disease. Genetic counseling provides patients with
information about their condition and helps them make informed decisions.(National Human Genome
Research Institute, National Institutes of Health (2000) "Glossary of Genetic Terms")
Genetic Screening: Testing a population group to identify a subset of individuals at high risk for having or
transmitting a specific genetic disorder. (National Human Genome Research Institute, National Institutes
of Health (2000) "Glossary of Genetic Terms")
Reference:

Alphabet Soup: Genetics for Genetics Consumers - Terms and Acronyms:
http://www.geneticalliance.org/ws_display.asp?filter=resources_alphabet_soup
International Genetic Alliance (Alliance - Europe)
No documents relating to genetic testing were found.
EGAN – Patients Networks for Medical Research and Health
No documents relating to genetic testing were found.
GIG - Genetic Interest Group (1998)
‘Genetic information’ is taken to mean any data of clinical relevance to the genetic status of an affected
or at risk individual. No distinction is made between, for example, family information arising from a
counseling session, phenotypic observations made during clinical evaluation or laboratory test results.
Medical genetics is an integrated service comprising clinical genetics and laboratory genetics (molecular
genetics, cytogenetics and biochemical genetics). Medical genetics overlaps with most other specialities
since mutant genes and chromosomal abnormalities may have pathogenic effects in any organ system
and at any age.
Reference:

Confidentiality Guidelines: http://www.gig.org.uk/docs/gig_confidentiality.pdf
GeneWatch
Documents, but no definitions found.
69
13. Policy, Ethics and Religious Organizations
SIBI - International Society of Bioethics
Documents, but no definitions found.
POST - Parliamentary Office of Science and Technology (2004) [27]
Despite no agreed definition, genetic testing generally refers to more direct testing, such as analysis of
the structure of DNA (cytogenetic testing) or changes within the DNA sequence itself (molecular testing).
Tests currently available
Genetic tests are used both before and after the appearance of disease symptoms. Tests to diagnose rare
inherited disorders, such as cystic fibrosis and Huntington’s disease, make up the vast majority of current
services. Testing techniques can now also be used to examine non-inherited conditions, for example,
analysing acquired changes in cancer tumours. Current uses of genetic tests include:
• diagnosing individuals with rare inherited disorders, where individuals inheriting a specific genetic
change will nearly always develop the associated disorder;
• identifying individuals with an inherited genetic change making them at high risk of a small sub-type of
some cancers, such as breast and bowel cancer;
• characterising leukaemias and tumours by analyzing acquired genetic changes;
• prenatal / neonatal screening of a foetus or newborn baby for conditions such as Down’s syndrome;
• examining whether genes are functional, as in tests for blood diseases such as sickle cell disease;
• carrier testing to test for the presence of a genetic change in healthy individuals (such as Fragile X, an
inherited learning difficulty) which may have implications for children or their relatives.
Pharmacogenetics
• potential: pharmacogenetics examines the relationship between genetic variation and an individual’s
response to medicine. It potentially marks a departure from the “one size fits all” approach to prescribing,
to one where the results of a pre-prescription genetic test guide subsequent drug selection and dosage
levels.
• challenges: age, gender and drug interactions also influence the effect of medicines. Stratifying patient
groups according to their genetic profile raises some clinical, regulatory and ethical questions. (Webster et
al, Nature Reviews Genetics, 5, No. 9 (in Press))
Pharmacogenetics will not impact on all drugs and early identification of relevant targets is needed.
• prospects: many clinical geneticists expect pharmacogenetics to drive the future expansion of genetic
testing services. However, a better evidence base is needed and it remains uncertain how the interests of
all relevant stakeholders (industry, clinicians, regulators and patients) can be met.
Preimplantation Genetic Diagnosis (PGD) uses in vitro fertilisation (IVF) to create embryos, tests one or
two cells from each embryo for the specific genetic abnormality and identifies unaffected embryos for
transfer to the uterus. The approach through PGD assists couples at risk of an inherited disorder to avoid
the birth of an affected child. The range of genetically transmissible conditions for which testing is
70
possible is continually increasing and examples licensed by the Human Fertilisation and Embryology
Authority for PGD include fragile X, muscular dystrophy, Huntington’s disease.
References:
 NHS GENETIC TESTING - Parliamentary Office of Science and Technology:
http://www.parliament.uk/documents/upload/POSTpn227.pdf
 Preimplantation Genetic Diagnosis (PGD) – Guiding Principles for Commissioners of NHS services:
http://www.cadasiltrust.org/assets/pdf/PGDNHSGuidelines.pdf
Nuffield Trust (2000)
There was general agreement in all the workshops that counselling was essential for patients both before
and after testing for single high penetrant genes and that it was the predictive power in these
circumstances that made it essential. Counselling had to be supportive and non-directive and had to take
care to avoid particular courses of action. Before agreeing to a test, patients had to understand their pretest risks of developing disease and how the test results might alter that risk for themselves and other
family members. They would also need to be informed about the range of preventive measures that were
available, or, in the case of prenatal testing, of reproductive choices.
Pharmacogenetics was the science by which our knowledge of the individual human genome would
explain how drugs affected individual patients, and how as a consequence of this knowledge, physicians
would be able to tailor interventions to the particular needs of their patients, both in terms of the choice
of drug and its dosage. The individualization of treatment would represent a more refined approach to
drug prescribing. At present it was not always possible to predict how a patient would react to a drug, at
what dosage level it should be given, how effective it might be, and whether the patient would suffer
adverse effects.
Reference:

The Nuffield Trust Genetics Scenario Project - Genetics and Health (May 2000):
http://www.archive.official-documents.co.uk/document/nuffield/policyf/gen-00.htm
Nuffield Council on Bioethics (2003) [28]
Genetic test - A test to detect the presence or absence of, or change in, a particular gene or chromosome.
This can be done directly, by analyzing the DNA of an individual, or indirectly, by examining the products
of their DNA, such as RNA or proteins. In some cases, the presence or absence of particular genes can be
determined by consideration of the family history of an individual, or simply by clinical observation.
Pharmacogenetic test - A test to detect the presence or absence of, or change in, a particular gene or
chromosome in order to predict response to a medicine. The test could examine inherited DNA or somatic
mutations in DNA.
Pharmacogenetics - The study of the effects of genetic differences between individuals in their response
to medicines. These differences may or may not be related to the disease being treated. The research
involves comparing the genotypes of individuals who have different responses to a medicine.
Pharmacogenomics - This term is not distinctly differentiated from pharmacogenetics, but implies the
examination of whole genomes or substantial numbers of genes in order, for example, to identify putative
targets for medicines or to identify large-scale differences in the patterns of gene expression in response
to chemical compounds.
71
Reference:

Pharmacogenetics – Ethical Issues, NCB (Sep 2003):
http://www.nuffieldbioethics.org/go/browseablepublications/pharmacogenetics/report_91.ht
ml]
Nuffield Council on Bioethics (1993)
All forms of genetic test aim to identify particular genetic characteristics but approach this in different
ways.
Chromosomal tests (cytogenetics) - Microscopic examination of chromosomes from cells in blood,
amniotic fluid or fetal tissue may be used to detect the chromosomal changes mentioned above. Until
recent years it was only possible to detect large alterations on a chromosome involving many genes, but
new techniques are making it possible to detect much smaller defects, allowing disorders involving only a
small amount of genetic material to be recognized.
Tests for disorders involving a single gene - Genes cannot be seen using the microscope, so in the past
tests for single gene disorders have been largely indirect, involving what the gene produces (protein), or
another substance affected by it, rather than the gene itself (see paragraph 2.15). Since the protein is still
unknown for the majority of genes, testing for single gene disorders has been very limited until recently.
Direct tests - A variety of techniques have now been developed for identifying important human genes
directly. There are two main approaches: (i) the gene may be isolated if the product (protein) it normally
produces is known. This approach was used for the genes involved with the main blood cell protein
haemoglobin (important for tests involving sickle cell disease and thalassaemias). The genes for some
metabolic diseases, where a specific chemical defect involving an enzyme was already known, have also
been isolated in this way; (ii) the gene may be isolated if its position on a chromosome is known
(positional cloning). This approach is increasingly successful in allowing genes to be isolated even when
we know nothing about their function or what protein they normally produce. One reason for this success
is that detailed genetic maps of the different chromosomes are being produced. This approach not only
pinpoints the chromosome region where the gene lies, but can provide genetic markers (identifiable
pieces of DNA) which lie close to the gene, and can enable an accurate test for a genetic disorder to be
made even before the gene itself is isolated.
Indirect (biochemical) tests - These tests detect not the gene itself, but some aspect of its function. The
most nearly direct are for the specific protein that the gene produces. In a genetic disorder tests may
show that the protein is not being made or is present in reduced amount; or it may be altered so that it
does not function adequately. Such tests are still important, for example, for abnormalities of
haemoglobin (in thalassaemia or sickle cell disease).
Carrier - A healthy individual who has both an abnormal and a normal copy of a pair of genes for a genetic
disorder or character or characteristic. A carrier of a gene for a recessive disorder will usually remain
unaffected through life.
Genetic disease or disorder - Conditions which are the result of alterations in the genetic make-up of an
individual.
They may be the direct consequences of defects in single genes (mutations); or in whole chromosomes,
parts of which may be lost, duplicated or misplaced; or from the interaction of multiple genes and
external factors.
Genetic fingerprinting - A technique which enables genetic relationships between close relatives, or the
identity of individuals to be established - usually beyond reasonable doubt.
72
Genetic map - The body of information on the relative positions of genes on chromosomes. Much of the
effort of the Human Genome Project is directed towards mapping chromosomes.
Reference:
 Genetic Screening Ethical Issues (Dec 1993):
http://www.nuffieldbioethics.org/go/ourwork/geneticscreening/publication_297.html
ACGT - Advisory Committee on Genetic Testing, Department Health, UK (1997) [29]
Genetic Test - A test to detect the presence of, or alteration in, a particular gene or chromosome
Genetic Testing - Testing used to detect the presence of, or alteration in, a gene, chromosome or a gene
product, in relation to a genetic disorder.
References:



ACGT First Annual Report (Jul 1996-Dec 1997):
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digi
talasset/dh_4014379.pdf
Code of Practice and Guidance on Human Genetic Testing Services Supplied Direct to the Public
(Sep 1997):
http://72.14.221.104/search?q=cache:7MD0H4dAGHwJ:www.amp.org/SACGHS/SACGHS030105.doc+Public+Comment+from+the+Association+for+Molecular+Pathology+presented+by
+Mary+Steele+Williams&hl=en&gl=uk&ct=clnk&cd=1
Genetic Testing for Late-Onset Disorders (Jul 1998):
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digi
talasset/dh_4014393.pdf
ELSI - National Institutes of Health and Department of Energy Task Force (2006) [30]
Genetic test - The analysis of human DNA, RNA, chromosomes, proteins, and certain metabolites in order
to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes.
Such purposes include predicting risk of disease, identifying carriers, establishing prenatal and clinical
diagnosis or prognosis. Prenatal, newborn, and carrier screening, as well as testing in high risk families,
are included. Tests for metabolites are covered only when they are undertaken with high probability that
an excess or deficiency of the metabolite indicates the presence of heritable mutations in single genes.
Tests conducted purely for research are excluded from the definition, as are tests for somatic (as opposed
to heritable) mutations, and testing for forensic purposes.
Reference:

The National Institutes of Health (NIH)-Department of Energy (DOE) Working Group on Ethical,
Legal and Social Implications (ELSI): http://www.genome.gov/10002393
PCSBI - US President’s Commission for the Study of Ethical Problems in Medicine and
Biomedical and Behavioral Research (1983)
Cytogenetics - The study of the structure and function of chromosomes.
73
Germ cell - A sperm or an egg, or a formative stage of either.
Somatic cell - One of the cells composing body tissues and body organs other than a germ cell.
Reference:

Screening and Counselling for Genetic Conditions - The ethical, social and legal implications of
Genetic Screening, Counselling and Education Programs:
http://bioethics.gov/reports/past_commissions/geneticscreening.pdf
CEC - Conference of European Churches
Documents, but no definitions found.
ICB – Institute of Catholic Bioethics
No documents relating to genetic testing were found.
14. Human Rights Associations
ACRU - American Civil Rights Union
No documents relating to genetic testing were found.
ACLU - American Civil Liberties Union (1998)
ACLU recommends that the appropriate definition of genetic information should cover: "Any information
about genes, gene products, or inherited characteristics that may derive from the individual or a family
member. This includes, but is not limited to, information regarding carrier status, information regarding
an increased likelihood of future disease or increased sensitivity to any substance, information derived
from laboratory tests that identify mutations in specific genes or chromosomes, physical medical
examinations, family histories, requests for genetic services or counseling, tests of gene products, and
direct analysis of genes or chromosomes." (National Taskforce on Civil Liberties in the Workplace)
Reference:

Testimony Presented to the Senate Labor and Human Resources Committee (1998):
http://www.workrights.org/issue_genetic/gd_house_testimony.html
74