Module C: Complex Diseases & Genetic Screening

Question 1

What is heritability?

Answer 1

measure of extent to which trait is determined by genetic factors

Question 2

How is heritability defined mathematically?

Answer 2

proportion of total variance in trait expression that is caused by genetic factors

Question 3

What tests can be undertaken to study heritability? (2)

Answer 3

adoption and twin studies (to study genetic vs. environmental conditions)

monogenic vs. fraternal twins

Question 4

What is recurrence risk?

Answer 4

probability of a child being affected with a disease given a positive family history of that disease

Question 5

How is recurrence risk calculated for Mendelian diseases?

Answer 5

can be calculated from pedigree and known mode of inheritance

Question 6

How is recurrence risk calculated for complex diseases?

Answer 6

recurrence risk must be calculated empirically from observations in large samples

Question 7

What is the relationship between recurrence risk and the risk of the trait in the population?

Answer 7

recurrence risk is proportional to the risk of the trait in the population

Question 8

What is the relationship between recurrence risk and the severity of presentation disease?

Answer 8

recurrence risk is proportional to the severity of presentation disease

Question 9

In what cases would recurrence risk of a disease be higher? (2)

Answer 9

higher if more than one family member has the disease

higher in relatives of patients who have the disease (even if the disease favors a particular sex)

Question 10

What is the relationship between recurrence risk and the risk of the disease appearing in a second degree relative?

Answer 10

recurrence risk is much lower in second degree relatives

Question 11

What is the utility of relative risk (λ)?

Answer 11

it can indicate genetic factors in the development of a trait

Question 12

What does a higher relative risk (λ) indicate?

Answer 12

if there’s a higher relative risk (λ) for a relative to develop the disease, then it means there is likely a greater genetic contribution to the disease

Question 13

What is the relationship between relative risk and autosomal dominant traits?

Answer 13

for autosomal dominant traits, the relative risk decreases by a factor of 2 with each more distant degree of relationship

Question 14

Compare the relative risk for siblings of a Mendelian disease and a complex disease.

Answer 14

relative risks for siblings are higher for Mendlian traits than for complex traits

Question 15

Define linkage.

Answer 15

inheritance of two genetic markers (either traits or DNA variants) together

Question 16

Define haplotype.

Answer 16

sequence of alleles in a block (on a chromosome)

Question 17

Define linkage disequilibrium.

Answer 17

occurrence of a group of alleles in a given haplotype at a frequency different than what would be expected from random association

Question 18

What is the purpose of genome-wide association studies?

Answer 18

attempt to identify particular markers or haplotypes associated with complex diseases

Question 19

Draw out the table associated with calculating screening test parameters. Write out the formulas for sensitivity, specificity, positive predictive value, and negative predictive value.

Answer 19