8/27/14 - Genetics of Complex Diseases

Question 1

Familial aggregation of a disease provides evidence of what?

Answer 1

A genetic component to a disease.

Question 1

What major environmental factor is associated with neural tube defects?

Answer 1

Folic acid deficiency

Question 2

What is discorance?

Answer 2

The presence of a certain trait in only one member of a twin pair.

Question 2

What is a monozygotic twin?

Answer 2

Identical twin; one zygote splits into two shortly after fertilization

Question 3

How would you interpret a relative risk ration

Answer 3

When

Question 4

How would you interpret a relative risk ratio >1?

Answer 4

When >1, there is likely a genetic component to the disease

Question 4

What is a modifier gene?

Answer 4

One gene that can modify the expression of another.

Question 4

How might a modifier gene influence incomplete penetrance?

Answer 4

It may completely silence a disease-causing gene, in which case the individual would not have clinical symptoms of the disease.

Question 5

Diseases where greater concordance is seen in monozygotic twins than dizygotic twins suggest what?

Answer 5

There is a genetic component to the disease.

Question 5

Why might there exist a complex and Mendelian form of Hirschprung disease?

Answer 5

Locus heterogeneity; either the loss/mutation of a single gene or a number of genes can lead to the same phenotype.

Question 7

What is a quantitative or continuous trait?

Answer 7

A trait with a variable phenotype; it is not simply present or absent (e.g. height).

Question 7

What is the most common mode of inheritance of retinitis pigmentosa?

Answer 7

Dominant

Question 9

How is the heritability of complex traits determined and why?

Answer 9

Empirical risk tables, since they can’t be predicted based on the principles of Mendelian inheritance.

Question 10

How might young women be at an increased risk for idiopathic cerebral vein thrombosis?

Answer 10

Oral concentrations increases blood plasma levels of factor X and prothrombin. Combined with mutations in the genes encoding Factor V and prothrombin, there is a 20-fold increase in susceptibility

Question 11

What were the findings in concordance studies between monozygotic twins reared together and apart?

Answer 11

They have similar concordance, suggesting that genetic factors are more important than environmental factors to a specific disease.

Question 13

What is the definition of relative risk?

Answer 13

A quantitative measure of the degree of familial aggregation of a disease.

Question 14

What is a qualitative or dichotomous trait?

Answer 14

A trait that is either present or absent, and is almost always attributable to different alleles of single genes.

Question 15

What is concordance?

Answer 15

The presence of a certain trait in both members of a twin pair.

Question 15

What is a dizygotic twin?

Answer 15

Fraternal twin; two eggs are fertilized by two sperm

Question 16

What is the relationship between variance and the contributions of genes and environment to quantitative traits?

Answer 16

Values near 0 imply that variability for a specific measurement is almost exclusively due to environmental factors. Values near 1 imply that variability is almost exclusively due to genetic factors.

Question 17

What gene is most commonly mutated in Hirschprung disease?

Answer 17

RET

Question 19

What is familial aggregation of a disease?

Answer 19

The occurence of a disease in more members of a family than can be explained by chance.

Question 20

Qualitative traits almost always follow the principles of which type of inheritance?

Answer 20

Mendelian

Question 21

How might a modifier gene influence variable expressivity?

Answer 21

It may reduce or increase expression of a disease-causing gene, leading to less or more severe symptoms, respectively.

Question 23

What is the role of MHC in type I diabetes?

Answer 23

Mutations in certain MHC genes result in an increased susceptibility to type I diabetes; MHC molecules are important in distinguishing cells of self and non-self, and diabetes is thought to be autoimmune.

Question 24

ROM1 and peripherin genes are often mutated in what disease?

Answer 24

Retinitis pigmentosa

Question 25

Diseases with less than 100% concordance in monozygotic twins suggests what?

Answer 25

Non-genetic factors play a role in the disease.

Question 27

What is the relationship between apolipoprotein E and Alzheimer’s disease?

Answer 27

Individuals who have at least one copy of the E4 allele of apolipoprotein E are 2-3 times more likely to develop Alzheimer’s than those who do not.

Question 28

What two genetic components result in increased susceptibility to idiopathic cerebral vein thrombosis?

Answer 28

Mutant alleles of the genes encoding factor V and prothrombin promote clotting.

Question 29

What is the relative risk ratio?

Answer 29

RRR (lambda) = prev. of disease in relatives of affected person / prev/ of disease in gen. pop.

Question 30

What is h2 heritability?

Answer 30

h2 = variance in DZ twins - variance in MZ twins / variance in DZ twins

Question 32

What are five common types or categories of congenital mutations?

Answer 32

1. Cleft lip with or without palate 2. Congenital heart defects 3. Pyloric ste 4. Hip dysplasia 5. Neural tube defects

Question 33

How can qualitative traits be inherited in a complex manner?

Answer 33

An underlying, polygenic susceptibility exists; above a certain threshold of susceptibility, the disease will manifest itself.

Question 34

What are two common mental disorders known to have a genetic component?

Answer 34

Schizophrenia, bipolar disorder