Patho-Ch.5

genes associated with breast cancer

BRCA 1/2, CHK2, ATM, PALB2, TP53

variations in angiotensinogen genes increase risk for

HTN

variation is caused by combined effects of multiple genes

polygenic

genes associated with type 2 DM

•n which encodes transcription for insulin, noted an association in 50% increase risk of developing DMT2. PPAR-Y, KCNJ11, variant of TCF7L2 (50% increase), glucokinase gene associated with maturity onset diabetes of young

alcholism and its recurrence

-- 3-5x greater in individual with an alcoholic parent -- 4fold increase even when raised w/nonalcoholic parents

recurrence risk for type 2 DM

-- MZ twins have 90% risk first degree relatives have 15-40% risk

recurrence risk criteria associated with multifactorial genes

-- RR increases if more than 1 family member is affected -- if expression of disease in proband is more severe then recurrence risk is higher -- if proband is of less commonly affected sex, then RR is higher -- RR for disease usually decreases rapidly in remotely related relatives

recurrence risk for schizophrenia

-- Recurrence risk among offspring of one affected parent is 10 times higher than the general population --If an individual has an affected sibling and an affected parent, then the risk is approximately 20%. --If an individual has two affected parents, then the risk is 50%.

recurrence risk increases in risk for breast cancer if:

-- first degree relative with breast cancer (risk doubles) -- increases if age of onset in affected relative is early and if cancer is bilateral

explain recurrence risk in colorectal cancer

-- risk is two to three times higher than the general population in those with one affected first-degree relative -- clusters in families

genes associated with alcholism

-ALDH2- excesive flushing, lightheadness, nausea, decreases alcholic state --> less likely to become alcoholics GABA receptors- calming effects --> susceptible to EtOH--> increase risk

genetic variations that promote autoimmunity are associated with type --- diabetes

1

chromosomes associated with BRCA2 and BRCA1

BRCA2- 13 BRCA1- 17 *- 50-80% risk of developing breast cancer and increases risk of ovarian cancer

mutlifactorial congenital malformations

Cleft lip, heart defects, hydrocephaly, neural tube defects, pyloric stenosis

shared by members of a twin pair

Concordant Trait

not shared by both members of a twin pair

Discordant trait

concordance rates for spina bifida are very different for monozygotic (0.72) and dizygotic (.33) twins? what does this indicate?

Spinda bifidahas sizable genetic component

variations in presenilin genes increase the risk for ----

alzheimers

Produces amyloid plaques and neurofibrillary tangles in the brain (cerebral cortex and hippocampus) and what is recurrence risk

alzheimers -- risk dobles if first degree relative has it

traits that have a ---- distribution usually are caused by additive effects of many genetic and environmental factors

bell shaped

second leading cause of death in US

cancer

coronary heart disease is caused by ------ and increase risk for what?

caused by atherosclerosis and can cause stroke or myocardial infarction

concordant vs discordant

concordant- Both members of a twin pair share a trait (always in monozygotic twins discordant- does not share trait

present at birth

congenital

variations in LDl receptor genes increase the risk for ----

coronary heart disease

leading cause of blindness, heart disease, and kidney failure

diabetes mellitus

driver vs passenger genes

drive- carry at least one driver mutation that increase cell growth advantage passenger- genes that undergo somatic mutations during tumorigenesis, but do not directly confer a growth advantage to cells

mutations/genes relating to alzheimers

early onset: presenilin 1 (PS1), presenilin 2 (PS2), and amyloid-beta precursor protein (APP) gene late onset: allelic variation in apolipoprotein E (APOE)

recurrence risks are calculated for single-gene disorders, but --- risks may be calculated instead for multifactorial disorders.

empirical

based on direct observation of data; specific multifactorial disease.

empirical risks

autosomal dominant condition caused by reduction in number of LDL receptors on cell surfaces

familial hypercholesterolemia

what does dizygotic mean?

fraternal twins rather than identical twins- do not look alike

genetic predisposition may interact with an environmental factor to increase the risk for a disease to a much higher level than either factor would alone

gene environment interaction

i wish people would quit telling me to exercise and stop smoking. That will not do me any good because my father died of a heart attack when he was only 52. i hear that tendency to heart attack is inherited, so i am doomed to die early.

good news is that although heart attacks have a genetic component, they also have environmental component. that means. you are not doomed. your health behaviors such as choosing to stop smoking and to exericse regularly can make a difference and reduce your heart attack risk.

Mr. Medlow's daughter has PKU, an autosomal recessive disorder. Is high BP autosomal recessive? a lot of my relatives have high BP but I exercise and diet to control my BP without drugs? is it really genetic?

high BP is not caused by specific mutated gene as PKU is. high BP is what we call a multifactorial genetic disorder which means that is caused by mutations in several genes and is affected by environmental factors such as diet and exercise. you are doing a great job managing your diet and exercise

environmental factors concering/increasing risk for colorectal cancer

high fat, low fiber diet, smoking

risk factor for heart disease, stroke, and kidney disease

hypertension -- 20-40% genetic; 60-80% environmental

monozygotic twins are also called --- twins

identical

(similar/in contrast to) most single gene disorders, occurrence of multifactorial disorders can change greatly from one population to another

in contrast

number of new cases of a disease reported during a specific period/by # of individuals in population

incidence rate

gene associated with obesity

leptin

according to threshold model, multifactorial diseases that are either present or absent must excess a -(distribution/liability) threshold before disease occurs

liability

what describes traits that do not follow bell curve distribution?

liability distribution-- low end of have little chance of getting disease and those on high end have greater chance

concordance rates for measles are similar for monozygotic. (0.95) and dizygotic (0.87) twins. what does that indicate

measles is unlikely to be influenced markedly by genes.

monozygotic vs dizygotic twins

monozygotic-Embryo divides to form two identical embryos. (identical) dizygotic- embryo divides to form two identical embryos. (50% same DNA)

recurrence risks for multifactorial disorders are higher if disease is (more/less) severe in proband

more

When laterality is a component, the bilateral forms ----

more likely to cluster in families

recurrence risks for multifactorial disorders are higher if (only, more than) one family member is affected

more than

many factors that can be measured numerically, such as BP, are (multifactorial, sex linked liability distributed)

multifactorial

variation is caused by combined effects of environment and genes

multifactorial

when both effects of multiple genes cause variations in traits.

multifactorial traits

nature vs nurture

nature- genetics nuture- environment

Presents a substantial risk factor for heart disease, stroke, cancer (prostate, breast, colon), and type 2 diabetes; strong correlation between parents/children

obesity

variations in leptin genes increase the risk for

obesity

difference between having one vs 2 copies of the ε4 allele in alzheimers?

one- 2-5x at greater risk two- 5-10x at greater risk

ØEffects of multiple genes cause the variations in traits.

polygenic traits

number of new cases of a disease reported during a specific period

prevalence rate

an individual with whom a pedigree begins is called a ---

proband

causes loss of heterozygosity in some regions and associated with several dozen polymorphisms and high fat diet

prostrate cancer

measures on continuous numeric scale following normal bell curve for distribution

quantitative traits

increased rate of a disease among individuals exposed to a risk factor divided by the incidence rate of the disease among individuals not exposed to a risk factor.

relative risk

variations in genes whose products interact with glutamate receptors increase the risk for ---

schizophrenia

Severe emotional disorder characterized by delusions, hallucinations, and bizarre, withdrawn, or inappropriate behavior

schizophrenia brain expressed gene who interact with glutamate and dopaminergic receptors

genes that affect bipolar affective disorder

serotonin, dopamine, and noradrenaline systems

incidence/recurrence risk for type 1 diabetes

siblings of individuals with type 1 DM face substantial elevation in risk incidence is higher in offspring of diabetic fathers

genes/mutations associated with colorectal cancer

somatic mutations inherited adenomatous polyposis coli gene mutations (tumor suppressor gene mutations)

research strategies used to estimate relative influence of genes and environment

twin studies and adoption studies

type 1 DM vs type 2 DM

type 1- insulin dependent -- autoimmune destruction of insulin producing beta cells in pancreas- juvenile onset (<40) type 2- insulin resistant/diminished production of insulin- associated with obesity, positive family history, lack of exericse, high carb diet

Cholesterol deposits in arteries and skin

xanthomas

recurrence risk of bipolar affective disorders

ØRisk rises between 5% and 10% if an individual has an affected first-degree relative, as compared with the normal risk of 0.5%. *60% risk due to genetic factors

risk for coronary heart disease increases if:

•more affected relatives exist. •affected relatives are female rather than male. •age of onset is younger than 55 years. RFs: Autosomal dominant familial hypercholesterolemia, high-fat diet, lack of exercise, smoking, and obesity increase risk