10/29 Genetics Flashcards
based on the is pedigree, what is the recombination rate between the autosomal recessive disease locus and the STR marker locus?
figure out which allele is in linkage phase and then count the number of times that this allele shows up without the disease being present. This is the number of recombinants and then take the # of recombinants and divide by the number of meiosis given by the parent!
What are a couple of disease examples that are multi-factorial
neural tube deffects! defects can lead to spinabifida (occulat, memingocele or myelominingocele) or anencephaly or encephalocele
how does spina bifida lead to hydrocyphilus?
it leads to a downward displacement of the cerebellar vermis (bottom of brain) and this leads to CSF problems
What is the best prevention of neural tube deffects?
folic acid supplementation.
what is the sib recurrence risk:
2-4% (so there is clustering in families)
How do we estimate the recurrence risk for multifactorial disease
estimated empirically
How is the recurrence risk for a multifactoriafl disease different then mendalian disease
use punnet square for mendalian and for multifactorial put together a cohort and then look at siblings and estimate the recurence (empirically determine)
the # of affected relatives increase how does it change recurrence risks for mutifactorial diseases?
up risk
how does the recurrence risk of multi-factorial disease change with severity of disease
up risk
how does the recurrence risk for multifactorial disease change if lower risk gender is the parent that is affected?
much higher risk
how is the threshold model of genetic multifactorial disease explain recurrence risk for these diseases?
explains the less affected gender affected parent etc. in short you need a whole bunch of risk factors to pile up to cause the disease!
if distant causin has neural tube deffect am I at more risk?
not so much falls off quick
what if neural tube deffects are very common in my population?
thaen risk for me is much higher.
how can we seperate the environmental and the genetic factors for a multi-factorial disease?
Twin Studies (Monozygotic W/100% genes same and dizygotic W/50% genes) and Adoption studies
the proportion of a trait’s variation that can be ascribed to genes
Heritability
how to measure heritability:
H= Cmz -Cdz / 1-Cdz (concordinance in mono vs. dizygotic) or estimate with H= 2(Cmz -Cdz)
what is the concordinance of a trait in twins
% of twins who share a trait.
mon twin concord is 47% and dia twin concord is 12% what is the heritability of this disease
70%
How does alcholism adoption studies show that genes play a strong role in this disease?
adopted offspring have same rate as those that are raised by alcoholics
how can disulfiram be used to treat alcoholism?
it can block ALDH that is a metabolism enzyme of alcohol and make it much less enjoyable to drink alcohol.
How can we find genes that underly multifactorial traits?
Find a subset where the disease is strongly inherited; Do linkage analysis; Do association studies; trials in animal models.
What would answer the question: “is a SNP allele more common in cases then controls?”
Association studies
why would the risk of coronary artery disease be higher if you have first degree relative, an early onset first degree relative, or an affected relative is female?
The multifactorial threshold model, early onset indicates more of a genetic factor, closer realative more shared genes
What are some traits of familial hypercholesterolemia?
LDL receptor mutations: high levels of LDL in hetero and very high (600mg/di) in homozygotes. 2-3 fold increase in MI in hetero and before 20 in homoz. they have deposits of fats at the knucles (Xanthomas)
how would you treat hypercholesteriolemia?
statins or liver transplant!
what are the common genes that lead to familial hypercholesterolemia?
LDL receptor mutations; Apolipoprotein B mutations. or PCSK9 gain of functinon (loss of function mutation would lead to low MI rates)
what does PCSK9 do to lead to MI?
It is a protease that will eat up the LDL receptors! so drugs that block this will lower cholesteral by alot even when on statins!
