Complex inheritence

Question 1

What is the difference between mutation, silent polymorphism and functional polymorphism?

Relative to effects in activity of the gene.

Answer 1

Mutation: DNA change that severely alters expression of a gene.

Silent polymorphism: silent change in DNA that doesn’t affect expression or activity of the gene.

Functional polymorphism: subtle changes that alter activity of gene and is still in normal range.

Question 2

How to calculate relative risk (relatives) and heritability?

Answer 2

(Prevalence of disease within the family of an affected individual) / (prevalence of disease in the general population)

Heritability

h^2 = (variance in DZ - variance in MZ)/ (DZ)

0 means not due to heritability. 1 means trait is entirely heritability.

Question 3

What is semi-dominant inheritance?

What is incomplete penetrance?

What is differential expressivity ?

Answer 3

It is still autosomal but it is not a binary yes or no. It is dependent on the number inherited. So two copies will be more severe than one copy.

Despite having the allele for a dominant autosomal disease, some people just don’t express it. It could mean that there are nongenetic factors at play.

Unlike incomplete which is yes or no for the disease, differential expressivity is different on a spectrum of severity. The exact same mutation yield different resutls.

Question 4

What is genetic linkage?

Answer 4

Essentially we have a polymorphic marker. And this marker is present in all those who have a disease and not those who don’t. Therefore we know approximately the location of the mutation. Then sequence the region. Look for similar mutations across other individuals who are affected. If there is a reoccurence, then this polymorphism causes the disease.

Question 5

What is Hirschsprung’s disease and what kind of inheritance is it an example of?

Answer 5

Hirschsprung is a developmental defect in the ganglia of the intestine which regulate peristalsis. What happens is food gets stuck and you get constipation in children.

This is an example of simple complex. A small handful of mutations contribute to the disease. Its not a one to one relationship. Majority will share just three specific mutations.

Question 6

Common diseases are multifactorial, what does that mean?

Answer 6

It means a trait is attributable to two or more genes (aka polygenic) and possibly including the environment.

The inheritance is complex which varying levels of genetic basis.

Question 7

What are association studies looking at common variants?

Answer 7

Its going backwards, looking at diseased individuals, you should see a polymorphism more frequently inherited by those with the disease. And the non SNP is inherited more often by those without the disease.

Question 8

What is penetrance

What is expressivity

What is heritability?

Answer 8

Penetrance = the fraction of individuals who carry an allele that show phenotypic manifestations of that allele (unaffected vs affected)

Expressivity = the extent to which an allele affects the phenotype (severity of affected)

Heritability = the degree of which genetic variance affects the population variance for a trait

Question 9

IF a condition is caused by autosomal dominant alleles, what would be concordance between MZ and DZ?

If condition was caused by autosomal recessive alleles, what would be concordance between MZ and DZ?

Answer 9

1. MZ=100%
   DZ = 50%
2. MZ = 100%
   DZ = 25%