JCCSS (KC)
Aspects of application of genetics
1.
Human genetics
2.
Plant and animal breeding
3.
Recombinant DNA technology and its application
4.
DNA fingerprinting and its forensic use
Human genetics
Previous knowledge related to human genetics:
1.
genes are vehicle of heredity and determine the phenotype of an organism
2.
the genetic material, DNA, is found in the nucleus of all cells
3.
chromosomes in the metaphase of cell division is visible under microscope
4.
inheritance of character determined by a single gene follows the pattern of Mendelian monohybrid cross
5.
mutation can occur at chromosomal or gene level resulting in changed phenotype (e.g. malformed red blood cells in sickle-cell anaemia; the typical physical features and varying degree of mental retardation caused by an extra chromosome in Down’s syndrome)
(1) Pedigree analysis (e.g. colourblindness)
(2) Genetic screening (e.g. detection of Down Syndrome)
(3) Prenatal and postnatal counselling of genetic diseases (e.g. glucose-6-phosphate dehydrogenase deficiency, thalassaemia)
(4) Gene therapy (a potential treatment of genetic diseases) ( e.g. cystic fibrosis)
(5) The implication of the Human Genome Project
(1) Pedigrees: Family Trees
• we need to analysis an existing population (especially for human) through an approach called pedigree analysis when
-- in situations that controlled crosses cannot be performed,.
-- with progeny data from several generations is limited and (
-- species with a long generation time.
• Is one of the central tasks of the human geneticist to study the inheritance of genes in humans.
• Pedigree analysis involves the construction of family trees
• Family history information is often collected at major family gatherings
• A pedigree is used to trace inheritance of a trait over several generations.
Symbols used in pedigree charts:
Once phenotypic data is collected from several generations and the pedigree is drawn , careful analysis may allow you to determine whether the trait is dominant or recessive . Also to know whether a phenotypically normal individual is a carrier of a recessive trait (especially some hereditary recessive disorder)or not

for counselling of genetic diseases .
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JCCSS (KC)
Three primary patterns of inheritance:
1.
autosomal dominant (For those traits exhibiting dominant gene action):
2.
autosomal recessive (F or those traits exhibiting recessive gene action):
3.
sex-linked (X-chromosomal)
Ref: http://www.ndsu.nodak.edu/instruct/mcclean/plsc431/mendel/mendel9.htm
http://web.ukonline.co.uk/webwise/spinneret/genes/pedigr.htm
Three primary patterns of inheritance:
Autosomal Dominant inheritance (DD or Dd) e.g.
Dwarfism, Huntington’s disease
Autosomal Recessive inheritance (rr) e.g. Albinism, Cystic fibrosis,
Sickle cell anaemia and
Thalassemia
X-linked recessive inheritance
(X r X r or X r Y) e.g. Colour-blindness, G-6-PD deficiency and
Haemophilia identification of dominant and recessive traits
Phenotype in majority of progeny : Affected
(Most of this type of affected individuals are heterozygous for this characteristic)
phenotype generally appears every generation
two affected parents may have unaffected progeny
affected progeny should have at least one affected parent (i.e. no unexpected affected progeny from normal parents)
Phenotype in majority of progeny : unaffected
appearance of phenotype may not be shown in every generation
two affected parents produce only affected children
many affected children have normal parents
(i.e. normal parents may have unexpected affected progeny  genetic counseling required )
**It is usually found in pedigrees with a high proportion of marriages between relatives e.g. cousins.
It is because the related parents have a greater chance of producing offspring that is homozygous for a particular recessive allele than unrelated parents.**
many affected boys have normal parents and many affected girls have normal mother
(i.e. normal parents may have unexpected affected progeny)
* Down’s Syndrome is not gene mutation as above. It is a kind of chromosome mutation
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Autosomal Dominant inheritance (DD or Dd) e.g. dwarfism, Huntington’s disease
Autosomal Recessive inheritance (rr) e.g. albinism, cystic fibrosis
JCCSS (KC)
X-linked recessive inheritance
(X r X r or X r Y) e.g. colour-blindness, G-6-PD deficiency and haemophilia
Is the affected phenotype related to sex?
No, the traits are expressed in both male and female in roughly equal number.
Yes,
phenotypic expression is much more common in males (who are hemizygous) than in females:
a normal male has all the daughter be phenotypically normal,
normal mother of affected boys should be carrier
an affected female has all the son be affected.
Homozygous normal mother has all boys and girls are normal
all affected girls has an affected father.
the occurrence of the affected trait in boys is independent of the phenotype and genotype of the father
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Colour blindness
Colour-blind people cannot see some or all colours. It is due to reduced number of some defect in one or more of the three types of cone cells. The most common form of defect is red-green colour blindness.
This is due to the lack of red or green cones. People who lack green cones cannot see green while people who lack red cones cannot see red. People who lack both green and red cones will see red and green as the same colour. Therefore, they are unable to distinguish between these two colours normally. It is common for such people to mistake brown as green or red.
Human beings seldom have total colour blindness, i.e. cannot detect any colours. If this is the problem, all objects seen by them appear in black and white only.
Colour blindness is a kind of sex-linked hereditary diseases, most patients are male and there is no cure for it at the present moment.
A possible Sex-Linked Pedigree of Red-Green colour blindness
• Color blind male (I) is father of "carrier" daughters and normal sons.
• Carrier daughters (II) have 50% chance to have color blind sons.
• Color blind male x carrier female can produce color blind daughters (IV)
By pedigree analysis we can:
Know whether a phenotypically normal female is a carrier or not.

This can be very important in giving imformation to a couple with a colour blind husband about genotype of the wife so that the couple can decide whether to have a baby or not.
Human Sex-Linked Traits
Colour blindness, deutan type
Colour blindness, protan type
Glucose-6-phosphate dehydrogenase deficiency
(G-6-PD deficiency)
Hemophilia A
Hemophilia B insensitivity to green light
Insensitivity to red light
Deficiency of glucose-6 –phosphate dehydrogenase; severe anaemic reaction following intake of primaquine in drug and certain food, such as fava bean
Classical form of clotting deficiency, lack of clotting factor VIII
Christmas disease, deficiency of clotting factor IX
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(2) Genetic screening
Ref : http://www.yourgenesyourhealth.org/ygyh/mason/ygyh.html?syndrome=ds&section=cause&video=0
Better understanding of the genetic basis of specific diseases will lead to earlier detection and improved methods of treatment of disease. Hence, identification of a gene and its corresponding influence on human characteristics allows for identification of that gene and its potential effects in both prenatal and postnatal beings. This is known as genetic screening.
Genetic screening is a process used to find out if a person / newborn (postnatal testing) has a genetic condition (carrier status screening) or disease ( diagnostic testing) or is likely to get the disease (predictive screening) or to detect any known genetic diseases that a foetus might inherit from his or her parents (prenatal testing).
Genetic screening involves genetic tests such as chromosome study or DNA analysis
- Techniques used in genetic screening:
1.
The analysis of blood or tissue samples taken from a newborn (Postnatal testing) or a person
2.
Prenatal testing i.
Amniocentesis 羊膜穿刺術 ii.
Maternal blood tests 母血測試 iii.
Ultrasound scans 超聲波掃描 iv.
Chorionic villus sampling (CVS) 絨膜絨毛檢驗 v.
Percutaneous umbilical blood sampling (PUBS) 經皮臍帶血採樣
However
• There is no single test that will detect the risk of any genetic disease in a couple’s offspring.
•
Genetic screening may help identify couples at risk for certain genetic disorders but not all birth defects.
•
Screening for genetic diseases that may affect offspring depends upon the racial or ethnic background of the couple,
• their family and medical history, and associated conditions.
Birth defects may occur that are not genetically based (e.g., environmental and toxic exposure, or random and unexplained) and may not be detected with genetic screening.
Diagnosis of Down’s syndrome is confirmed with testing of karyotype 核型測試 by Amniocentesis and Chorionic villus sampling (CVS):
It is quite common for expectant mothers of an advanced age to have fetal cells (at particular stage of pregnancy) examined to check for a trisomy of chromosome 21 which will result in Down's syndrome (as the affected foetus has 47 chromosomes in the nucleus and chromosomes in the metaphase of cell division is visible under microscope).

Many parents want to know this information so they can make informed decisions about the pregnancy .
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JCCSS (KC)
(3) Prenatal and postnatal counselling of genetic diseases
Genetic counselling can be defined as the counselling that deals with the problems of giving advice to people faced with a diagnosis of genetic disease or families having or likely to have children with genetic disorders.
( People seeking genetic counselling may be newly diagnosed patients, new parents or couples planning a pregnancy, or family members concerned that they too may carry a disorder.)
- Treatment of genetic disorders is available for only a few disorders and this is where genetic counselling finds its importance in diagnosis and prevention of disorders.
-- Pre-pregnancy counseling is very important, and women should consult their physician or other primary caregiver prior to conception, or at least very early in the first trimester, so as to determine any risk factors for genetic diseases; e.g. familial disorders such as cystic fibrosis, muscular dystrophy, hemophilia, sickle cell anemia, thalassemic , Tay-Sachs Disease or chromosomal disorders, the most common being Downs Syndrome (Trisomy 21).
( For families who have been identified at risk for these or other hereditary diseases, carrier states can then be detected prior to conception or early in the pregnancy. )
- Various diagnotic methods are employed for this purpose
-- Appropriate diagnostic tools may be utilized as described before: pedigree analysis, blood sampling, chorionic villus sampling, amniocentesis and high resolution ultrasound.
The purposes of genetic screening and counseling
The counselling aims to help people to understand both the factual information about the disease and the effect it will have on their lives (e.g thalassemic patients who may have to receive blood transfusion for life) , so that they can reach their own decisions about the future.
Crucially, genetic counselling is non-directive, supporting people in reaching their own decisions, based on their own unique medical and social circumstances.
In H.K.: http://www.info.gov.hk/dh/ar0001/pdf/ch_04_7.pdf
http://www.info.gov.hk/dh/main_ser/index.htm
1. Prenatal counseling inform the prospective parents:
- based on their family histories of genetic diseases, about the risk of giving birth to offspring bearing genetic diseases (e.g. thalassaemia) and to explain their causes.
- whether the foetus is suffering from some genetic diseases
(e.g. screened for Down’s syndrome in expectant mothers of an advanced age )
 To help prospective parents make informed decisions, e.g. whether to terminate the pregnancy for a foetus with the genetic disorder.
2. Postnatal counseling help parents to take appropriate care of the affected children and to provide proper treatment
(all newborns in Hong Kong have postnatal screening for G6PD deficiency , parents are provided with information on what types of drugs and food to be avoided in raising G6DP deficient / glucose-6-phosphate dehydrogenase deficient children).
Ethical concern about genetic counselling
1. Genetic counselling touches very deeply on human emotions of guilt, grief and fear, and on deeply felt moral beliefs.
2. Counsellors are trained to help people through the inevitable emotions that a diagnosis arouses – and which ripple through the whole family because of their shared genetic inheritance.
3. No two patients are the same, and genetic counselling has to be sensitive to the fact that a diagnosis can have very different meaning to different people.
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( 4) Gene therapy - a new method for correcting genetic diseases
Gene therapy is a novel approach to treating diseases based on modifying the expression of a person’s genes toward a therapeutic goal. Gene therapy is most often been discussed in the context of treating lethal and disabling diseases although it also has a potential for disease prevention. With an 11 year history of clinical trials, there is some recent evidence that gene therapy may be efficacious in the treatment of certain single gene deficiency diseases. Nevertheless, gene therapy remains a highly experimental collection of technologies whose full potential is yet to be realized.
Gene therapy is the use of modern genetic engineering (employs the techniques of DNA recombination and transplantation) as an attempt to treat genetic disease that cannot be treated by conventional medicine.
Potential use of gene therapy
•
With the advancement of the Human Genome Project, more and more genes associated with genetic diseases will be found out.
•
If these diseases are found to be caused by recessive genes in which the damages are confined to accessible tissues, gene therapy by gene supplementation could be a promising treatment.
•
Gene therapy is not restricted to recessive, single-gene defects only, but also has a great potential in treating cancers and infectious diseases (e.g. AIDS).
Genetic diseases that can potentially be treated by gene therapy:
•
Haemophila
•
Thalassaemia
•
Sickle-cell anaemia
•
Cystic fibrosis (CF)
• Phenylketonuria (PKU)
• Severe combined immunodeficiency disease (SCID)
Method of gene therapy
Introduction of selected foreign gene(s) into the patient / replacing the defective genes in cells of the patient with the normal one so that the cells can function normally to produce necessary products.
The foreign gene that has been introduced into an organism is known as a transgene, and the organism possessing the foreign gene is said to be transgenic.
A successful and effective DNA transplantation plays an essential role in the gene therapy. Depending on the type of the target cell or the disease, the method and the efficiency of DNA transplantation are different. Here are some common methods for gene transplantation:
(I) (a) In vitro gene transfer
It refers to the transfer of normal copies of a gene into cells from an affected individual in culture, followed by in vitro culture and re-introduction of the genetically modified cells to the affected individual.
(b) In vivo gene transfer (e.g. gene therapy on cystic fibrosis)
The normal functional gene is incorporated into a viral carrier (retrovirus or adenovirus -- with harmful genes removed) or enclosed in liposomes (spheres of lipid bilayer constructed artificially), and then transferred directly into the tissue of patients
(II) (a) somatic-cell gene therapy
This method will cure the disease of an affected individual, but the defective gene will still be present in germ cells and transmitted to the offspring.
(b) Germ-line gene therapy the functional gene could be passed to the next generation.
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Limitation of gene therapy
• 1. The functional gene may not be integrated into right positions in the chromosome in somatic-cell gene therapy.
• 2. Germ-line gene therapy arise a lot of ethical dilemma and is unlikely to be approved by the law. (prohibited in
Britain)
• 3. Any more ??? :
• die of treated cells  repeat treatments to replace the dead cells
• difficulty in deal with stem cells
• use of retrovival vector  risk of mutation caused by insertion of viral DNA into chromosome
Social concerns caused by genetic screening and gene therapy
Concern Questions
Reliability Are genetic screening and gene therapy reliable?
Are healthcare professionals well prepared for the new genetic technology ?
Do healthcare professionals properly inform parents about the limitations of genetic screening and risks in gene therapy? e.g. effect of removal of dominant disorder (disorder due to gain of function or neutralization) alleles
Ethical issues
Should prospective parents have the right to test their foetuses for genetic diseases ?
Should prospective parents have the right to terminate the pregnancy if the foetuses are found to have genetic diseases ?
Should we have the right to alter the genes / alter human genome of future generations ?
Controversy arises from gene therapy
If an infant is found to have genetic defects before birth, can gene therapy be applied? There is still a long way to go in using human bodies in the therapy. At this stage, only congenital anemia and congenital immunity deficiency can be treated by the technology. The benefits of gene therapy are believed to be on the near horizon; however, the side effects it brings need to be paid attention to:
1. The structure of genes cannot be entirely altered in the application of gene therapy. Hence even when the mother can successfully deliver the baby, the infant who has undergone the therapy is unlikely to grow healthily.
2. In the process of replacing missing or defective genes, false replacement may occur.
3. Once the genome is altered, as a result, there will be great differences in physical characteristics between the forebears and the offspring.
Since the impacts of gene therapy are tremendous, government, academia and the public are encouraged to freely express their views on the therapy in order to raise the awareness of controversial ethical and legal issues raised among scientists.
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(5) The implication of the Human Genome Project (HGP)
The Human Genome Project (HGP) began in 1990 as an effort by researchers from around the world to map and sequence the human genome - the totality of human DNA - as well as the genomes of important experimental organisms, like yeast, the nematode worm, and mouse.
In 2000, the collaborators in the HGP announced the completion of a draft revealing 90% of the human sequence and in February 2001, the initial analysis of the human genome sequence was published in the scientific literature.
The researches of the HGP include
• 1. Determine the complete nucleotide sequences that make up human DNA
(i.e. the sequence of the entire human genome)
• 2. Identify all of the genes in human DNA
• 3. Store the information in databases.
• 4. Develop tools for DNA data analysis
• 5. be aware of the ethical implications
 Objective and future task of HGP: - to identify all the genes on every chromosome in the human body;
- to find out the exact function of each gene in the human body; and
- seek for any potential benefits and possible application of the findings in different fields.
• The project was originally planned to last 15 years. Due to the rapid technological advances and the effort of scientists, the project was completed in April 2003 (50 yrs after Watson and Crick discovered the structure of DNA). The finished human genome sequence will cover all portions of the genome that are accessible to modern sequencing technology.
The genome will be sequenced to approximately 9-fold redundancy; the sequence will be at least 99.99% accurate.
Potential application of the HGP ( http://www.lxyz.net/teacher/ayd/_private/renleijiyinzujihua.htm )
1.
Molecular medicine
2.
Risk assessment
3.
Evolution and human migration
4.
DNA forensics ( http://dna.lifelaw.com.tw/iden.asp
)
Human Genome Study and Implications (on ethical, legal…issues)
• 1. If the genome study obtain a franchise, how can we protect the right of the poor?
• 2. Now, the main area of application of the genome study is for medical purpose. However, with the same technique, it is also possible to manipulate genes for other purposes, such as increasing the longevity of life and I.Q. If then, is it ethical to create such "perfect" human beings?
• 3. Is it ethical to change the genes of other plants and animals? What are the risks behind?
• 4. It may be possible to prepare a tailor-made health-care program for each individual according his or her genes.
• 5. Will the privacy of individuals be respected?
• Scientists are quite optimistic towards the new technology, whereas others are not. Humanists consider that these are not ethical. Moreover, other social problems like employment, insurance (Insurance companies have the rights to genetic test results?), etc., may also arise.
Other possible problems are:
1.People may form groups according to their genetic make up
2.New health policy
3.Speed up the evolution process
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Other opinions
1.If the government can set up proper laws, genetic engineering may be beneficial.
2.It is a norm to employ the most talented, there is nothing wrong about it.
3.If we put ourselves into the shoes of the insurance company, there is nothing wrong about the company's use of the genetic information to set up the insurance fees.
4.Why is cloning human not ethical?
5.If parents want their children to have better genes, why do we have to stop them from seeking help from genetic engineering?
6.Perfect offspring: If parents employ genetic engineering to perfect their children's genes, the children then no longer inherit what their parents have. So the traditional concept of biological parents is blurred. Moreover, parents cannot be sure whether their children welcome the idea that their genes are being manipulated.
Moreover, people may be treated in an unfair way because of the differences in their genetic make-up.
Ed suggested reference:
1. The Human Genome Project – Exploring the Scientific and Humanistic Dimensions http:// www.mcet.edu/genome/ index.html
2. Your genes, your choices http://www.ornl.gov/hgmis/publicat/genechoice/index.html
http://www.ornl.gov/sci/techresources/Human_Genome/publicat/genechoice/contents.html
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