Nurs 337:Genetics

  1. Gatekeeper Genes P53
    genes produce proteins that regulate the growth of tumors inhibiting mitosis and enhancing apotosis
  2. Care taker Genes
    • maintain integrity of the genome
    • mismatch repair genes such as BRCA 1 and colon cancer.
  3. Inherited/ Germline
    • Directly passed on to future generations because it is in every cell
    • Cancer develops when a second mutation occurs in a somatic cell in the affected body part
  4. Sporadic/ Acquired
    • Isolated; the causative mutation occurs only in cells of the affected tissue
    • Somatic Mutation (nonsex cells)
    • Not directly passed on to future generations
  5. Oncogenesis
    • multistep process resulting from the accumulation of numerous genetic mutations that cause uncontrolled cellular growth
    • Checkpoints in cancer cells are thought to be weak or deficient
    • Alteration in apotosis
  6. Breast Cancer
    • Personal history of breast cancer an or ovarian before age 50
    • Relative with male breast cancer Both breast and ovarian cancer
    • Clusters in family
    • Affected or unaffected women or men with a maternal or paternal blood relative with mutant gene
    • Risk is always greater for first degree relatives of affected individuals
    • Cancer is two succeeding generations within the family, autosomal dominant inheritance of caner predisposition is likely
    • Also many hereditary cancers has reduced penetrance
  7. Cancer
    • may develop when an environmental trigger causes mutations in a somatic cell (sporadic) or when a somatic mutation compounds an inherited susceptibility (germline)
    • All cancer is result of accumulated inherited and/or acquired genetic mutations causing:
    • 1. oncogene activation
    • 2. tumor suppressor gene inactivation
    • 3. production of telomerase
  8. Breast and ovarian
    BCRA1 and BCRA 2
  9. Colon
    MLH1, MSH2, and MSH6
  10. Knudson Theory
    • 2 hit theory
    • 1. single hit by DNA damage
    • 2. second hit in the undamaged chromosome pair is required gene function is lost
    • 3. mechanism is important in P53 gene – tumor suppressor gene
    • Need at least 4 bad genes for cancer
  11. retinoblastoma
    • The most common eye cancer in children
    • Life-threatening cancer of the retina
    • Usually discovered in babies from 6-24 mos
    • Develops from a single affected cell in the retina and it is invisible at its inception
    • Later a small white nodule is noted in the retina (not visible to parents or affecting the child)
  12. Colon cancer
    • Hereditary nonpolypsis colorectal cancer
    • Autosomal dominant
    • Germline mutations in mismatch repair genes
    • Develop cancer between 40-50 yrs ( diagnosis between 14-82 yrs)
    • High risk of developing other cancers
    • FAP – patients have hundred of polyps
    • Defect in the APC gene
    • Genetic testing done as early as 10-12 yrs of age
    • Pt ‘s with inflammatory bowel disease are at risk for colorectal cancer approximately 8-15 yrs after diagnosis Colorectal cancer is the second leading cancer causing death
  13. What is teratoma?
    • germ cell tumor derived from pluripotential cells and made up of elements of different types of tissue from one or more of the three germ cell layers.
    • Congenital (present at birth– not inherited)
    • Teeth/ hair/ etc. – ewwies picture in ppt.
  14. Pharmacogenetics
    Study of how genetic differences in a SINGLE gene influence variability in drug response (i.e., efficacy and toxicity)
  15. Pharmacogenomics
    Study of how genetic (genome) differences in MULTIPLE genes influence variability in drug response (i.e., efficacy and toxicity)
  16. P450
    • Hepatic system
    • Enzymes known as the super family
    • Oxidizing many chemicals and drugs
    • Subfamilies groups
    • Vary in ethnic groups
    • Poor metabolizers break down drug slowly
    • Ultra metabolizers process drug more quickly
  17. CYP
    • § CYP2D6 is responsible for the metabolism of a number of different drugs
    • § Antidepressants, antipsychotics, analgesics, cardiovascular drugs
    • § Over 100 polymorphisms in CYP2D6 have been identified
    • § Based on these polymorphisms, patients are phenotypically classified as:
    • § Ultrarapid metabolizers (UMs)
    • § Extensive metabolizers (EMs)
    • § Stays in body for a really long time
    • § Poor metabolizers (PMs)
  18. Skizo
    • § •The neurotransmitter system
    • § ( GRM3 responds to neurotransmitter)
    • § •Metabolism
    • § •Genetic changes & deletions
    • § identical twins 50%, non identical 15%, 1% general pop
  19. Autism
    • § •First description in the 1940’s
    • § •Range of disorders: poor social interaction, failure to develop appropriate peer relationships, language and developmental delays, and lack of flexibility with routines
    • § •Genetic susceptibility might depend on combinations of an unusually large number of genes ( 20 or >)
    • § •New mutations
    • § 25% change if DiGeorge’s
  20. Bipolar
    • § •About 1% of the US population suffers from bipolar disorders
    • § •Age of onset can be as early as adolescence, often occurs in
    • § •20s and 30s
    • § •Males and females similar hyperactivity, acceleration of thought process, low attention span, creativity and feelings of elation and
    • § •power
    • § •Many manic depressives are highly creative people “thin line that separates genius and madness”
    • § • Manic depressive have unique patterns of metabolism and blood flow in the prefrontal cortex-a part of the brain associated with intellect
  21. MAOH
    • § aggressive behavior gene
    • § a single gene mutation
    • § an inborn error of metabolism
    • § persons are basically functional - but have improper control of behavior
  22. general research mental disorders
    MAOH,Bipolar, Autism, Skizo
  23. Drugs
    • § Absorption, distributions, metabolism (liver), elimination (kidney)
    • § We want to give the lowest dose given the best effect with the less toxicity
  24. narcolepsy
    • o •Daytime sleepiness with tendency to rapidly fall
    • o asleep (narcolepsy) and periods of muscle weakness (cataplexy)
    • o •Genetic contribution is indicated:
    • o - 0.02-0.06% general population in US and Europe
    • o - 1-2% risk with first degree relative
    • o - 25-31% concordance among MZ twins
    • o •Model of narcolepsy in dogs:
    • o -Fully penetrant autosomal recessive trait due to
    • o allele at gene canarc-1.
  25. Stem cell
    • § Embryos produce early stem cells called totipotent
    • § Blastocyst stage- embroyonic stem cells in are called pluripotent
    • § Fetal stage of human development- stem cells called pluripotent
    • § Umbilical cord blood and adult stem cells called multipotent
Card Set
Nurs 337:Genetics
Final Spring 2011