Making babies: Genetically Correct

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Making babies Genetically Correct

• Zhi Hua Ran
• The department of Gastroenterology
• Ren Ji Hospital

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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)
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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
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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
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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 high-throughput 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.
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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
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Discover the DNA structure

• 1953---James Watson/Francis Crick

Double-helix structure of DNA
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Biography---James Watson
Born in Chicago, April 6, 1928
His fathers ancestors were originally of English
descent
His mothers father was Scottish-born taylor
married to a daughter of Irish immigrants who
arrived in the US about 1840
Spent entire boyhood in Chicago
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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
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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
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Biography---James Watson
19531955 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
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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
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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 X-ray
diffraction by a helix
1962, The Nobel Prize in Physiology or Medicine
Died at 2004
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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
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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
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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
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The Human Genome Project---more powerful tools
Durg development, customizing drugs to individual
genetic profiles
Earlier diagnosis of disease
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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
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In Vitro Fertilization---history
1y
The first test-tube baby
Louise Brown born in England in July 25, 1147
PM, 1978
25 y
With parents
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In Vitro Fertilization---history
Dr. Patrick Steptoe
At birth
Oldham General Hospital
Dr. Robert Edwards
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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
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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
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In Vitro Fertilization
Phase 3
The third phase involves fertilization of the eggs
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ICSI---Intracytoplasmic sperm injection
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1
2
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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
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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
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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
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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
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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
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Prenatal Genetic Analysis
Heterozygosity testing for recessive disease
could only be attempted for eugenic purposes
Gregor Mendel 18221884
Mendels law of independent assortment ?????????
Mendels law of segregation ???????
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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 Huntingtons disease
Presymptomatic testing for estimating the risk of
developing adult-onset cancers and Alzheimers
disease
Confirmational diagnosis of a symptomatic
individual
Forensic/identity testing
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Gene testing---HD
Huntingtons disease (HD) Usually midlife onset
progressive, lethal, degenerative neurological
disease
Caused by a single abnormal gene
An autosomal dominant disorder
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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
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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
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Pre-implantation diagnosis
Single cell analysis
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Technology RT-PCR
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Technology --- RT-PCR
Electrophoresis
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DNA microarray
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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
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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.
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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
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Ethical challenges
Potential to creat embryos for medical purposes
Potential to select embryos
Potential to modify embryos
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Potential to modify embryos
Alteration of genetic traits Beauty/handsome,
longevity, healthy
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Potential to select embryos
A girl or boy, you pick?
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We can test for lots of things, the question is,
should we?
Ethical challenges
--- Dr. Mark Hughes