Nurs_337_Genetics

tumor suppressor genes that directly regulate cell proliferation

genes produce proteins that regulate the growth of tumors inhibiting mitosis and enhancing apotosis

• maintain integrity of the genome
• mismatch repair genes such as BRCA 1 and colon cancer.

• 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

• Isolated; the causative mutation occurs only in cells of the affected tissue
• Somatic Mutation (nonsex cells)
• Not directly passed on to future generations

• 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

• 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

• 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

BCRA1 and BCRA 2

MLH1, MSH2, and MSH6

• 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

• 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)

• 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

• 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.

Study of how genetic differences in a SINGLE gene influence variability in drug response (i.e., efficacy and toxicity)

Study of how genetic (genome) differences in MULTIPLE genes influence variability in drug response (i.e., efficacy and toxicity)

• 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

• § 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)

• § •The neurotransmitter system
• § ( GRM3 responds to neurotransmitter)
• § •Metabolism
• § •Genetic changes & deletions
• § identical twins 50%, non identical 15%, 1% general pop

• § •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

• § •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

• § aggressive behavior gene
• § a single gene mutation
• § an inborn error of metabolism
• § persons are basically functional - but have improper control of behavior

MAOH,Bipolar, Autism, Skizo

• § Absorption, distributions, metabolism (liver), elimination (kidney)
• § We want to give the lowest dose given the best effect with the less toxicity

• 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.

• § 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