Genomic Medicine Senior Leadership Brazos November 3, 2005

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Genomic MedicineSenior Leadership
BrazosNovember 3, 2005

• Nancy W. Dickey, MD
• Roderick E. McCallum, PhD
• Texas AM Health Science Center

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Some interesting tidbits

• We dont know precisely how many genes the genome
  contains but current data indicate that there are
  30,000-35,000 genes
• Mutations that cause disease have been identified
  in approximately 1000 genes
• Some chromosomes are gene dense (17, 19, 22) as
  compared to others (4, 8, 13, 18)
• Only 2 of the human genome codes for proteins
  though through alternative splicing, over 100,000
  proteins can be derived from these genes
• More than 50 of the human genome represents
  repeat sequences of several types whose function
  is poorly understood
• A complex array of molecular signals allows
  specific genes to be turned on (expressed) or
  turned off in specific tissues at specific times

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A few terms

• Genomic medicine
• A term coined 15 years ago
• Study not just of single genes but of the
  functions and interactions of all the genes in
  the genome, the interactions of multiple genes
  and the impact of the environment

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And more termsgenetics

• The study of single genes and their effects
• A genetic test is the analysis of human DNA, RNA,
  or chromosomes for clinical purposes
• Most available genetic tests address questions
  related to rare or uncommon diseases
• Genetic tests can be done to diagnose genetic
  disease (often in newborns), identification of
  future health risks, assessment of risks to
  future children
• Identification of carrier status (recessive)
• Identification does not necessarily mean
  treatment options Huntingtons Chorea can
  predict with nearly 100 effectiveness but not
  treat (Valley of the Dolls)
• Genetics for preventive care is emerging but
  remains problematic e.g. BRCA1 and 2 mutations in
  breast and ovarian cancer but lifetime risk
  estimates range from 26-85

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Terms continued

• Proteomics
• Proteins are called by some the machines of
  molecules
• Proteomics is a variety of things all of which
  are aspects of understanding proteins, their
  spatial structure, cataloguing or mapping their
  structure in particular membranes
• Proteomics is the study of how proteins are
  modified by enzymes, genetics, chemical
  interactions, etc.
• Proteomics is the study of protein-protein
  interactions and qualitative and quantitative
  changes arising under a variety of influences

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Pharmacogenomics

• Many things influence effects of medications
  including age, organ function, other drugs,
  nature of the disease and genomics
• There are more than 30 families of
  drug-metabolizing enzymes in humans and
  essentially all have genetic variants
• ¾ of whites and ½ of blacks have a genetic
  inability to express the CYP3A5 family of P-450
  enzymes
• If medications are equally metabolized by both
  CYP3A5 and CYP3A4, it is difficult to see the
  problem.
• For medications metabolized substantially more by
  CYP3A5, the inability to express the enzyme could
  mean problems with some medications
• Children with acute lymphoblastic leukemia often
  receive mercaptopurine but 1/300 patients has a
  mutation of a gene that can cause the drug to
  cause serious, even fatal, side effects gene
  testing can lead to reduced dosages and fewer
  problems
• A future is visualized when genetic testing might
  help determine which medication is best for you

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Dilemma posed by genetics/genomics.

• Misuse of information to deny access health
  insurance, employment, loans
• Dilemma of privacy vs. right to know
• Daughter of man with diffuse adenomatous
  polyposis her right to know vs. his right to
  privacy

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Texas Institute for Genomic Medicine - TIGM

• Created by the Governors Enterprise Fund
• Driven by the desire to participate in the KOMP
  (Knock Out Mouse Project)
• Approximately 20,000-30,000 genes with more than
  95 similarity to humans
• Individually knock out each gene creating mice
  missing a particular gene (30,000 different mice!)

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Genomic Medicine by Mouse

• Take the mice minus a gene and give them a souped
  up executive physical find out what works
  better or worse or not at all when THAT gene if
  missing
• Create targets for pharmaceuticals, models to
  understand human disease, and so on

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TIGM

• Scientists at Texas AM University and at the AM
  Health Science Center will have exceptional
  opportunity to be at the cutting edge of genomic
  medicine
• But as you can see from the depiction at the
  right and the numbers throughout none of the
  answers will be available tomorrow