Genetic Basis for Complex Diseases Flashcards Preview

Week 8- SHANE > Genetic Basis for Complex Diseases > Flashcards

Flashcards in Genetic Basis for Complex Diseases Deck (18):

What is heritability?

proportion of phenotypic variability that can be attributed to genetic

traits that are largely determined by genes will have heritability approaching 1


What is the term for traits that are either present or absent?



Is risk a continuous spectrum?



What happens to the risk curve of family members of affected people in comparison to the risk curve of the general population?

shift to the right. i.e. the potential to pass the threshold is elevated and they are at an elevated risk


What aspects of family history influence risk of multifactorial disease?

1) Degree of relationship- drops off rapidly after immediate family

2) Number of affected family members

3) Severity of disease expression

4) Associated conditions in family members-i.e. atopy has an increased risk in association with asthma

5) age of relative at onset- younger onset= higher risk


Are multifactorial diseases more or less common than mendelian diseases like CF and Huntington's

more. risk is roughly 1 in 1000 for multifactoral diseases (rough number but a good basis)


For multifactorial disease, is the associated risk of having a disease based on a immediate family member having the disease higher or lower than population risk?

Is it higher or lower than mendelian risk in a similar situation (i.e. one affected family member)

higher than population risk but still much lower than a similar situation with a mendelian disease


What happens to the risk in a multifactorial disease when a 2nd degree family member is involved?

It drops rapidly (say from 4% in the 1st degree to 0.7% in the second)

this is different from mendelian which would only drop off by half (say from 4% to 2%)
due to a single further meiosis occurring


When does the risk of a multifactoral disease based on family relationship drop to near population risk?

3rd degree of relation


Does the threshold model address cause?



What happens to risk when more family members are affected by a multifactoral disease?

it goes up rapidly (say from 4% w/ 1 affected family member, 12% with 2, and 25% with three)


Which have larger risks to relatives, mendelian or complex risk diseases?



Which are more common, mendelian or complex risk diseases?

complex risk diseases (think asthma vs CF)


Which show more variability in symptoms, mendelian or complex risk diseases?

complex risk


Which show younger onset of disease, mendelian or complex risk diseases?



For diabetes, which are a better predictor of risk, risk genes or phenotypic data?

phenotypic data


What is the concept of 'missing heritability'

complex diseases are very often impacted by risk genes (which are highly heritable) but they show little phenotypical correlation to the prevelance/risk of many diseases like diabetes

i.e. the highest risk gene for diabetes only increases risk by 30%


What is the take home message of a Manolio graph?

alleles that are common in the population won't show high penetrance or have that large of a detrmental impact, while rare alleles will show higher penetrance (i.e. CF)