Making babies:
Genetically Correct
Zhi Hua Ran
The department of Gastroenterology
Ren Ji Hospital
A Glossary of Genetics Terms
Gene: basic unit of inheritance for all living organisms
Genome: Genetic endowment of a species
Gene mapping: Determining location of genes on chromosome
Gene sequencing: Determining identity of genes from the
distinctive order (sequence) of base pairs, such as A-T and G-C
Chromosome: Threadlike structure in the nuclei of plant
and animal cells; it carries the linearly arranged genetic
units (genes)
A Glossary of Genetics Terms
Nucleic acid: Large, chainlike molecule of phosphric acid,
sugar and purine and pyrimidine bases
Marker: Gene with a known location on a chromosome
Template: Macromolecular model for another macromolecule,
as in the synthesis of RNA from a DNA template
Transgenic: Organism, such as a mouse, containing
experimentally transferred genetic material from another
organism, such as mammal
Mutation: Abrupt change in the genotype of an organism
that is not the result of recombination
A Glossary of Genetics Terms
Recombination: Formation in offspring of genetic
combinations not present in parents
Genotype: The genetic constitution of an individual
Phenotype: The observable characters of an organism; the result
of the way the genes are expressed
Genetic defect: Pathological changes that occur by
duplication, deletion or rearrangement of DNA
Transcription: The process by which RNA is formed from
DNA
Nucleotide: The structural unit of nucleic acid
A Glossary of Genetics Terms
RT-PCR: Reverse transcriptase polymerase chain reaction
Gene therapy: A technique for correcting defective genes responsible
for disease development
DNA microarray: An experimental tool for obtaining highthroughput gene expression data
Stem cell: have the remarkable potential to develop into many different
cell types in the body. Serving as a sort of repair system for the body, they
can theoretically divide without limit to replenish other cells as long as the
person or animal is still alive. When a stem cell divides, each new cell has
the potential to either remain a stem cell or become another type of cell
with a more specialized function, such as a muscle cell, a red blood cell, or
a brain cell.
Milestones of Genetics
Discover the double-helix structure of DNA---by
James Watson and Francis Crick
Create the first recombinant DNA molecule---by
Paul Berg
Mapping the human genome---The Human
Genome Project, completed in 2001
Discover the DNA structure
1953---James
Watson/Francis Crick
Double-helix structure
of DNA
Biography---James Watson
Born in Chicago, April 6, 1928
His father‘s ancestors were originally
of English descent
His mother‘s father was Scottish-born
taylor married to a daughter of Irish
immigrants who arrived in the US
about 1840
Spent entire boyhood in Chicago
Biography---James Watson
Study at University of Chicago at 1943
In 1947, received a B.Sc.degree in
Zoology
During these years, his boyhood interest
in bird-watching had matured into a
serious desire to learn genetics
In 1950, received Ph.D degree in
Zoology at Indiana University
His Ph.D thesis was a study of the effect
of hard X-rays on bacteriophage
multiplication
Biography---James Watson
In the spring of 1951, he change his
direction of his research toward the
structural chemistry of nucleic acids
and proteins
Met Crick at 1952, common
interest in solving the DNA
structure
Solved in early March, 1953---the
proposal of the complementary
double-helical configuration
Biography---James Watson
1953~1955 at the California Institute
of Technology as Senior Research
Fellow in Biology
1956, Assitant Professor, Harvard
Biology Department
1958, Associate Professor
1961, Professor
1962, The Nobel Prize in Physiology
or Medicine
Biography---Francis Crick
Born on June 8, 1916 at
Northampton, England
In 1937, obtained a B.Sc. In Physics
at London
Started to learn biology in 1937,
interrupted by World War Two
During the war, he worked as a
scientist for the British Admiralty
Left the Admiralty in 1947 to study
biology
Biography---Francis Crick
Joined the Medical Research Council
Unit since 1949
Restarted in 1950, obtained Ph.D in
1954
Worked out the general theory of Xray diffraction by a helix
1962, The Nobel Prize in Physiology
or Medicine
Died at 2004
Biography---Paul Berg
Born on June 30, 1926, New York
Gained early recognition/influence when he
delineated the key steps in which DNA
produces proteins
Best known for his development of a
technique for splicing together DNA from
different types of organisms.
His achievement gave scientists a tool for
studying the structure of viral chromosomes
and the biochemical basis of human genetic
diseases.
Awarded the Nobel Prize for Chemistry in
1980
The Human Genome Project
Began at 1990
Founded by US department of Energy (DOE), US
National Institute of Health (NIH) in collaboration
with Britains Wellcome trust
Draft sequence was published in 2001
The Human Genome Project
Celera Genomics, a private company based in
Maryland, is publishing its findings in Science.
A public international effort, led by the United
States, is publishing its analysis of the genome in
Nature, a British journal.
Human have about 30,000 genes
Genetic differences between any two
people are relatively small
The Human Genome Project--more powerful tools
Durg development, customizing drugs to
individual genetic profiles
Earlier diagnosis of disease
In Vitro Fertilization---history
The technique was developed in the UK by Dr. Patrick Steptoe
and Robert Edwards
First “test tube“ baby: In UK, Louise Brown (July,1978
Second “test tube“ baby: In India, Kanupriya Agarwal by Dr.
Mukhopadhyay (Oct, 1978)
The first in US: Elizabeth Carr by Dr. Howard and GS Jones
(1981)
Since then, IVF has exploded in populatiry, accournts 1% of all
birth, 115,000 in total in US
In Vitro Fertilization---history
1y
The first “test-tube “ baby
Louise Brown born in England
in July 25, 11:47 PM, 1978
25 y
With parents
In Vitro Fertilization---history
Dr. Patrick Steptoe
At birth
Oldham General Hospital
Dr. Robert Edwards
In Vitro Fertilization
Phase 1:
The first phase consists of stimulating the ovary with hormones
injected, in order to cause several eggs to mature
Normally, only one egg matures per menstrual cycle, so
additional hormones are usually required to prevent the body
from negatively to this excess of eggs
The last injection given is that of human chorionic
gonadotropin (hCG), the hormone normally produced during
pregnancy
In Vitro Fertilization
Phase 2:
The second phase, that of egg retrieval,
occurs about 34-36 hours after the hCG
injection
The entire procedure usually takes
8-20 mins
In Vitro Fertilization
Phase 3:
The third phase involves fertilization of the eggs
ICSI---Intracytoplasmic sperm
injection
3
1
2
In Vitro Fertilization
Phase 4:
Phase four is the actual embryo replacement
A pregnancy test usually is done 12-14 days after retrieval
2 Cell embryo
4 Cell embryo
8 Cells embryo
Thumbing through the
encyclopedia of life
Technology often drives science, science drives
medicine, and medicine is always pushing society
in to ethical corners
Dr. Mark Hughes
Prenatal Genetic Analysis
One of the ethically most problematic applications
of genetics
If detected in the fetus, are incurable, may lead to
selective abortion
Prenatal diagnosis of genetic traits typically can
only provide information to assist the prospective
parents in their decision making whether to carry
the pregnancy to term or to terminate it
Prenatal Genetic Analysis
It requires both a medical indication and informed
conset of the parents
Parents have a right to refuse medically indicated
prenatal diagnosis even if there is a high risk for
fetal condition that is incompatible with life
There are a few genetic traits (such as gender) are
accessible to prenatal diagnosis today but unrelated
to health
Prenatal Genetic Analysis
Prenatal diagnosis is carried out only to give parents and physicians
information about the health of the fetus
The use of prenatal diagnosis for paternity testing, except in cases of
rape or incest, or for gender selection, apart from sex-linked disorders,
is not acceptable
WHO 1998
Prenatal Genetic Analysis
Heterozygosity testing for recessive disease could only be attempted for
eugenic purposes
Gregor Mendel
1822~1884
Mendel‘s law of independent assortment
孟德儿独立分配定律
Mendel‘s law of segregation
孟德儿分离定律
Novel parameters for prenatal
selection--- gene testing
Carrier screening, which involves indentifying unaffected individuals
who carry one copy of a gene for a disease that requires two copies for
the diasese to be expressed
Preimplantation genetic diagnosis (screening Embryos for disease)
Newbone screening
Presymptomatic testing for predicting developing 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
Gene testing---HD
Huntington‘s disease (HD):
Usually midlife onset; progressive, lethal, degenerative neurological
disease
Caused by a single abnormal gene
An autosomal dominant disorder
Gene testing---SMA
One of the neuromuscular diseases. Muscles weaken and waste away (atrophy)
due to degeneration of motor neurones which are nerve cells in the spinal cord
Gene was located Proximal portion of the long arm of chromosome 5 , 1990
Gene testing--- Fanconi Syndrome
A disorder in which the
proximal renal tubules of the
kidney do not properly
reabsorb electrolytes and
nutrients back into the body
Excessive drinking, urination
and glucose in the urine
Muscle wasting, acidosis and
poor condition will also occur
Pre-implantation diagnosis
Single cell analysis
Technology:
RT-PCR
Technology --- RT-PCR
Electrophoresis
DNA microarray
Gene therapy
A normal gene may be inserted into a nonspecific
location within the genome to replace a nonfunctional
gene. This approach is most common
An abnormal gene could be swapped for a normal gene
through homologous recombination
The abnormal gene could be repaired through selective
reverse mutation, which returns the gene to its normal
function
The regulation of a particular gene could be altered
Dr. Mark Hughes
A Professor and Director of Molecular
Medicine and Genetics at Wayne State
University and Director of the Genomics
Center Hub for the State of Michigan's Life
Sciences Corridor.
His work has centered on understanding
gene expression in the early human embryo
He pioneered the field of PGD for couples at
very high reproductive genetic risk and offers
this technology in conjunction with IVF
Centers in the U.S. and Canada.
Ethical challenges
Bypassing the natrual method of conception
Creating life in the laboratory
Fertilizing more embryos than will be needed
Discarding excess embryos
Unnatural environment for embryos
Contributes to overpopulation
Ethical challenges
Potential to creat embryos for medical purposes
Potential to select embryos
Potential to modify embryos
Potential to modify embryos
Alteration of genetic traits:
Beauty/handsome, longevity, healthy
Potential to select embryos
A girl or boy, you pick?
Ethical challenges
We can test for lots of
things, the question is,
should we?
--- Dr. Mark Hughes