Human Genome
Project
Potential Applications
In March, 2002
Doctors successfully screened embryos
for gene mutation linked to early onset
Alzheimer's
JAMA, March, 2002
A Great Success
Basics
Inside the nucleus of every cell in the
body, a complex set of genetic
instructions, known as the human
genome, con...
Chromosomes are long chains of
DNA-deoxyribonucleic acid.
Base code
Hereditary instructions are written in
a four-letter code, with each letter
corresponding to one of the
chemical...
Gene
A gene is a chromosomal region
capable of making a functional
transcript.
Thus
A genome is all the DNA in the cell,
including its genes.
Errors in genes--the smallest units of
heredity-- may cause...
However
Many genes are co-expressed with their
own antagonist
The result
All diseases have a genetic component,
whether inherited or resulting from the
body's response to environmental...
Genomics
Structural genomics: to identify all the
approximate 30,000 genes in human
DNA
Functional genomics: to understand...
Objectives
determine the sequences of the 3 billion
chemical base pairs that make up
human DNA,
store this information in ...
The concept
How & Which
genes play a role in disease
causation
Tools
An increasing number of gene tests are
becoming available commercially
Micro-array composed of five separate
array e...
Genomic Medicine
Diagnosis
Monitoring of progress
treatment of disease
Prevention
Example
Using tools emerging from the Human
Genome Project, an international team
tracked the gene for hereditary
nonpolyp...
But
The road from gene identification to
effective treatments is long and full of
challenges
So Why?!!!
We as Doctors must be aware about
the new genetic era and its potential
impacts on our specialty so as to offer...
Implantation : the model
Repeated failure of implantation was
linked to Leukemia inhibitory Factor
gene (LIF)
However,
Implantation
Micro-array analysis has shown 36 up-
regulated genes and 27 down-regulated
genes at the implantation site.
R...
Categorised in
genes with recognized roles in
implantation,
genes with potential roles in this
process
genes whose functio...
Polycystic Ovary
Syndrome
the insulin gene called variable number
tandem repeat (VNTR) gene appears to
be a promising cand...
Polycystic Ovary
Syndrome
follistatin gene as a potential disease
locus implicated in ovarian follicular
development
Polycystic ovary
syndrome
CYP11a gene -encoding P450 side
chain cleavage-appears to be a major
susceptibility locus for st...
MUC 1: a genetic link to
infertility?
Women with unexplained infertility were
found to have a genetic susceptibility to
fa...
Inherited breast and ovarian cancer
(BRCA 1 and 2; early-onset tumors of
breasts and ovaries)
Pre-eclampsia
A polymorphism in the gene for
microsomal epoxide hydrolase is
associated with pre-eclampsia
Zusterzeel et a...
Women with the glutathione S-
transferase P1b-1b genotype, which
could result in lower glutathione S-
transferase detoxifi...
Gynecological oncology
The increased ovarian cancer risk
associated with the high-activity of
human EPHX gene (epoxide hyd...
Cystic Fibrosis
three hundred affected children born each year
in UK
Although improvements in care and treatment mean that...
Currently Available
DNA-Based Gene Tests
Some Alpha-1-antitrypsin deficiency
Alzheimer's disease
Cystic fibrosis
Ataxia telangiectasia
Gaucher disease
Inherited breast and ovarian cancer
Hereditary nonpolyposis colon cancer
Charcot-Mar...
Duchenne muscular dystrophy/Becker
muscular dystrophy
Fanconi anemia
Factor V-Leiden
Fragile X syndrome
Hemophilia A and B...
Phenylketonuria
Adult Polycystic Kidney Disease
Prader Willi/Angelman syndromes
Sickle cell disease Spinocerebellar ataxia...
Gene Therapy
It means modification of the genetic
material of living cells
This applies to genetically determined
diseases...
Highly promising
Treatment
Prevention
Immunity enhancing (e.g., by adding a
gene that suppresses tumor growth).
Still experimental
more technological barriers are
encountered than foreseen and
therefore, the clinical success up to now...
How
Cells may be modified ex vivo for
subsequent administration to patients,
or may be altered in vivo by gene
therapy giv...
Germ cell gene therapy
Two techniques
Deposit corrective
genes in the cell’s
nucleus,
integrate genes into
the chromosomes..
Somatic cell gene
therapy
Vector
Viral genes targeting
the cell's nucleus
are retained in the
vector, while harmful
viral genes are
removed and
repl...
Steps
Viruses recognize and attach to
receptors (a) and work their way
through, into the cell (b). Once inside,
the virus ...
Specific Target
Each virus is particularly adapted to use
one or a few specific receptors, which
limits the range of cells...
Familial
Hypercholesterolemia
A corrective low-
density lipoprotein
(LDL) receptor gene.
A piece of the
patient's liver wa...
Is it the future!!!
gene therapy for single-gene diseases
may be routine and successful in 20
years.
Role in oncology
• It has been proven that many cancers are
caused by the mutation of certain genes or
lack of gene functi...
Cancer Gene Therapy
• The RIZ1 gene is the best example
• has potent tumor suppressive activities in
causing apoptosis, G2...
May be in the future
Patients with cancer may receive
combination chemotherapy together
with gene therapy for six cycles o...
Gene Therapy: Simple
in Theory but Difficult
in Practice
Obstacles
Safety
Costs
Ethics : Baby designers
all of the current approaches to gene therapy seek to introduce the good gene into the so-called
somatic cells of a child ...
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
Genomics for Obstetrics & Gynecology
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Genomics for Obstetrics & Gynecology

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Genomics could be difficult to understand for gynecologists. In this talk we will try to make it simple .

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Genomics for Obstetrics & Gynecology

  1. 1. Human Genome Project Potential Applications
  2. 2. In March, 2002 Doctors successfully screened embryos for gene mutation linked to early onset Alzheimer's JAMA, March, 2002
  3. 3. A Great Success
  4. 4. Basics Inside the nucleus of every cell in the body, a complex set of genetic instructions, known as the human genome, contained on pairs of chromosomes.
  5. 5. Chromosomes are long chains of DNA-deoxyribonucleic acid.
  6. 6. Base code Hereditary instructions are written in a four-letter code, with each letter corresponding to one of the chemical constituents of DNA: A, G, C, T.
  7. 7. Gene A gene is a chromosomal region capable of making a functional transcript.
  8. 8. Thus A genome is all the DNA in the cell, including its genes. Errors in genes--the smallest units of heredity-- may cause or contribute to disease
  9. 9. However Many genes are co-expressed with their own antagonist
  10. 10. The result All diseases have a genetic component, whether inherited or resulting from the body's response to environmental stresses like viruses or toxins
  11. 11. Genomics Structural genomics: to identify all the approximate 30,000 genes in human DNA Functional genomics: to understand gene-gene interaction
  12. 12. Objectives determine the sequences of the 3 billion chemical base pairs that make up human DNA, store this information in databases explore potential application in practical life
  13. 13. The concept How & Which genes play a role in disease causation
  14. 14. Tools An increasing number of gene tests are becoming available commercially Micro-array composed of five separate array each of which has about 10,000 target
  15. 15. Genomic Medicine Diagnosis Monitoring of progress treatment of disease Prevention
  16. 16. Example Using tools emerging from the Human Genome Project, an international team tracked the gene for hereditary nonpolyposis colon cancer to a region of chromosome 2.
  17. 17. But The road from gene identification to effective treatments is long and full of challenges
  18. 18. So Why?!!! We as Doctors must be aware about the new genetic era and its potential impacts on our specialty so as to offer our patients the most appropriate and informed care.
  19. 19. Implantation : the model Repeated failure of implantation was linked to Leukemia inhibitory Factor gene (LIF) However,
  20. 20. Implantation Micro-array analysis has shown 36 up- regulated genes and 27 down-regulated genes at the implantation site. Reese J et al, 2001
  21. 21. Categorised in genes with recognized roles in implantation, genes with potential roles in this process genes whose functions have yet to be defined in this event
  22. 22. Polycystic Ovary Syndrome the insulin gene called variable number tandem repeat (VNTR) gene appears to be a promising candidate
  23. 23. Polycystic Ovary Syndrome follistatin gene as a potential disease locus implicated in ovarian follicular development
  24. 24. Polycystic ovary syndrome CYP11a gene -encoding P450 side chain cleavage-appears to be a major susceptibility locus for steroidogenic abnormalities Franks et al, 2001
  25. 25. MUC 1: a genetic link to infertility? Women with unexplained infertility were found to have a genetic susceptibility to failure of embryo implantation due to small MUC 1 allele size. Horne A, et al,2001
  26. 26. Inherited breast and ovarian cancer (BRCA 1 and 2; early-onset tumors of breasts and ovaries)
  27. 27. Pre-eclampsia A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia Zusterzeel et al 2001
  28. 28. Women with the glutathione S- transferase P1b-1b genotype, which could result in lower glutathione S- transferase detoxification capacity, has been linked to higher susceptibility to preeclampsia Zusterzeel 2000
  29. 29. Gynecological oncology The increased ovarian cancer risk associated with the high-activity of human EPHX gene (epoxide hydrolase)
  30. 30. Cystic Fibrosis three hundred affected children born each year in UK Although improvements in care and treatment mean that people with cystic fibrosis can now live for up to twenty-five years, there is no cure
  31. 31. Currently Available DNA-Based Gene Tests Some Alpha-1-antitrypsin deficiency Alzheimer's disease Cystic fibrosis
  32. 32. Ataxia telangiectasia Gaucher disease Inherited breast and ovarian cancer Hereditary nonpolyposis colon cancer Charcot-Marie-Tooth Congenital adrenal hyperplasia
  33. 33. Duchenne muscular dystrophy/Becker muscular dystrophy Fanconi anemia Factor V-Leiden Fragile X syndrome Hemophilia A and B Huntington's disease Myotonic dystrophy Neurofibromatosis type 1
  34. 34. Phenylketonuria Adult Polycystic Kidney Disease Prader Willi/Angelman syndromes Sickle cell disease Spinocerebellar ataxia Spinal muscular atrophy Thalassemias Tay-Sachs Disease
  35. 35. Gene Therapy It means modification of the genetic material of living cells This applies to genetically determined diseases but also to diseases that occur later in life
  36. 36. Highly promising Treatment Prevention Immunity enhancing (e.g., by adding a gene that suppresses tumor growth).
  37. 37. Still experimental more technological barriers are encountered than foreseen and therefore, the clinical success up to now is limited.
  38. 38. How Cells may be modified ex vivo for subsequent administration to patients, or may be altered in vivo by gene therapy given directly to the subject.
  39. 39. Germ cell gene therapy
  40. 40. Two techniques Deposit corrective genes in the cell’s nucleus, integrate genes into the chromosomes..
  41. 41. Somatic cell gene therapy
  42. 42. Vector Viral genes targeting the cell's nucleus are retained in the vector, while harmful viral genes are removed and replaced with the corrective gene.
  43. 43. Steps Viruses recognize and attach to receptors (a) and work their way through, into the cell (b). Once inside, the virus discharges its contents (c). Viral genes progress through the cell and into the nucleus (d).
  44. 44. Specific Target Each virus is particularly adapted to use one or a few specific receptors, which limits the range of cells each one can infect.
  45. 45. Familial Hypercholesterolemia A corrective low- density lipoprotein (LDL) receptor gene. A piece of the patient's liver was removed, and the cells were treated with a retrovirus carrying a good copy of the gene. Cells with the corrective gene were reimplanted into the patients's liver.
  46. 46. Is it the future!!! gene therapy for single-gene diseases may be routine and successful in 20 years.
  47. 47. Role in oncology • It has been proven that many cancers are caused by the mutation of certain genes or lack of gene function • The introduction of those genes into cancer cells where gene function is compromised, can work to restore gene function and stop tumor progression
  48. 48. Cancer Gene Therapy • The RIZ1 gene is the best example • has potent tumor suppressive activities in causing apoptosis, G2/M arrest, or both. • Preclinical animal studies have shown that a recombinant adenovirus expressing the gene, AdRIZ1, can suppress the growth of colon cancer Canote 2002
  49. 49. May be in the future Patients with cancer may receive combination chemotherapy together with gene therapy for six cycles of treatment and, at that point, the chemotherapy is stopped and patients continue with chronic maintenance biologic therapy Ozols 2002
  50. 50. Gene Therapy: Simple in Theory but Difficult in Practice
  51. 51. Obstacles Safety Costs Ethics : Baby designers
  52. 52. all of the current approaches to gene therapy seek to introduce the good gene into the so-called somatic cells of a child or an adult.

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