10/29 Genetics

Question 1

based on the is pedigree, what is the recombination rate between the autosomal recessive disease locus and the STR marker locus?

Answer 1

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!

Question 2

What are a couple of disease examples that are multi-factorial

Answer 2

neural tube deffects! defects can lead to spinabifida (occulat, memingocele or myelominingocele) or anencephaly or encephalocele

Question 3

how does spina bifida lead to hydrocyphilus?

Answer 3

it leads to a downward displacement of the cerebellar vermis (bottom of brain) and this leads to CSF problems

Question 4

What is the best prevention of neural tube deffects?

Answer 4

folic acid supplementation.

Question 5

what is the sib recurrence risk:

Answer 5

2-4% (so there is clustering in families)

Question 6

How do we estimate the recurrence risk for multifactorial disease

Answer 6

estimated empirically

Question 7

How is the recurrence risk for a multifactoriafl disease different then mendalian disease

Answer 7

use punnet square for mendalian and for multifactorial put together a cohort and then look at siblings and estimate the recurence (empirically determine)

Question 8

the # of affected relatives increase how does it change recurrence risks for mutifactorial diseases?

Answer 8

up risk

Question 9

how does the recurrence risk of multi-factorial disease change with severity of disease

Answer 9

up risk

Question 10

how does the recurrence risk for multifactorial disease change if lower risk gender is the parent that is affected?

Answer 10

much higher risk

Question 11

how is the threshold model of genetic multifactorial disease explain recurrence risk for these diseases?

Answer 11

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!

Question 12

if distant causin has neural tube deffect am I at more risk?

Answer 12

not so much falls off quick

Question 13

what if neural tube deffects are very common in my population?

Answer 13

thaen risk for me is much higher.

Question 14

how can we seperate the environmental and the genetic factors for a multi-factorial disease?

Answer 14

Twin Studies (Monozygotic W/100% genes same and dizygotic W/50% genes) and Adoption studies

Question 15

the proportion of a trait’s variation that can be ascribed to genes

Answer 15

Heritability

Question 16

how to measure heritability:

Answer 16

H= Cmz -Cdz / 1-Cdz (concordinance in mono vs. dizygotic) or estimate with H= 2(Cmz -Cdz)

Question 17

what is the concordinance of a trait in twins

Answer 17

% of twins who share a trait.

Question 18

mon twin concord is 47% and dia twin concord is 12% what is the heritability of this disease

Answer 18

70%

Question 19

How does alcholism adoption studies show that genes play a strong role in this disease?

Answer 19

adopted offspring have same rate as those that are raised by alcoholics

Question 20

how can disulfiram be used to treat alcoholism?

Answer 20

it can block ALDH that is a metabolism enzyme of alcohol and make it much less enjoyable to drink alcohol.

Question 21

How can we find genes that underly multifactorial traits?

Answer 21

Find a subset where the disease is strongly inherited; Do linkage analysis; Do association studies; trials in animal models.

Question 22

What would answer the question: “is a SNP allele more common in cases then controls?”

Answer 22

Association studies

Question 23

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?

Answer 23

The multifactorial threshold model, early onset indicates more of a genetic factor, closer realative more shared genes

Question 24

What are some traits of familial hypercholesterolemia?

Answer 24

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)

Question 25

how would you treat hypercholesteriolemia?

Answer 25

statins or liver transplant!

Question 26

what are the common genes that lead to familial hypercholesterolemia?

Answer 26

LDL receptor mutations; Apolipoprotein B mutations. or PCSK9 gain of functinon (loss of function mutation would lead to low MI rates)

Question 27

what does PCSK9 do to lead to MI?

Answer 27

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!