Lecture 2.3 (not on exam 1): Multifactoral disorders

Question 1

1) What is complex inheritance?
2) Give examples
3) Are these diseases common?

Answer 1

1) What we say about diseases that appear to “run in families” but don’t follow Mendelian inheritance patterns
2) DM, MI, Alzheimer’s
3) Two in three individuals at some point during their lifetime

Question 2

True or false: with multifactorial familial inheritance, there is a complex interplay between environment and genetic endowment that potentially involves numerous genes that have an effect on disease

Answer 2

True

Question 3

What makes multifactorial inheritance diseases different?

Answer 3

1) It’s not just one or two alleles
2) The inheritance pattern is “complex”
3) The etiology is “multifactorial”

Question 4

Families share much of their genetic material and their environmental exposures. Therefore, family members share what? (2 things)

What does this lead to?

Answer 4

1) Gene to gene interactions
2) Gene to environment interactions
-Hence, disease tends to “run in families”

Question 5

Qualitative vs. Quantitative Trait: Define each and give examples

Answer 5

1) Qualitative: You have it or you don’t
-Lung cancer, arthritis, color blindness
2) Quantitative: You have a certain amount of it that is measurable
-Height, hypercholesterolemia, hypertension, obesity

Question 6

Define concordance

Answer 6

Pertains to a pair of relatives regarding both types of traits:
1) They both share a qualitative trait or
2) They share a quantitative trait that is similar in magnitude

Question 7

Define discordance

Answer 7

Pertains to relative pair regarding both types of traits:
1) One of them has a qualitative trait that the other does not or
2) They have values of a quantitative trait that are at opposite ends of the distribution

Question 8

True or false: the more closely related two individuals are in a family, the more alleles they have in common, the more distant the relative the less they have in common

Answer 8

True

Question 9

True or false: all alleles are the same in monozygotic twins

Answer 9

True

Question 10

What are examples of first-degree relatives?

Answer 10

1) Parent and child
2) Siblings
3) Di-zygotic twins

Question 11

Familial aggregation in qualitative traits:
1) Math would dictate that if an allele increases the chance of developing a disease, we would expect what about families?
2) What is this called? Explain.

Answer 11

1) An affected individual would have a greater number of affected relatives than the general population
2) This is called “familial aggregation of disease”
-Because mutated alleles cause genetic disease, and families share alleles, disease aggregates in families

Question 12

This aggregation of qualitative traits in families can be measured what two ways?

Answer 12

1) Relative Risk Ratio: Compare the frequency of dz in relatives of affected proband with prevalence in general population
2) Family history and case-control studies: Compares the “positive family history” in patients with the disease to ‘control families’ of similar demographic

Question 13

1) Define familial aggregation in quantitative traits
2) How is this different from qualitative traits?

Answer 13

1) The more alleles contributing to a given range of quantitative trait, the more that family displays its measured traits within that range
2) You’re measuring an average range that pertains to the trait

Question 14

Give an example of familial aggregation in quantitative traits

Answer 14

Height is not something that you either have or do not have, but it does deviate from the mean in groups of family members

Question 15

What we see when familial aggregation in quantitative traits is measured is what? Give an example

Answer 15

1) A degree of correlation (reflected by “the coefficient of correlation = r”)
2) Example: We claim to have a positive correlation in the following case: Cholesterol is measured in a group of people. For those individuals in that group with high cholesterol, we see that the higher their cholesterol is, the higher it also is in their family

Question 16

1) Define genetic variance
2) Define environmental variance

Answer 16

1) The phenotypic variance of a trait in a population that is attributed to genotypic differences
2) The phenotypic variance of a trait in a population that is attributed to differences in the environment

Question 17

1) Define heritability of quantitative trait
2) How is it measured?

Answer 17

1) The fraction of the total phenotypic variance of a quantitative trait that is due to allelic variation in the broadest sense
2) Measured from 0 to 1: The higher it is, the more that genetic inheritance contributes to disease
1 = totally genetic
0 = not genetic at all

Question 18

1) _______________ among twins is a powerful tool for studying genetic influence.
2) Define this term

Answer 18

1) Concordance
2) Agreement between traits exhibited by both twins

Question 19

Define twin study

Answer 19

Study of monozygotic (MZ) and dizygotic (DZ) twins.

Question 20

In twin studies, the degree of concordance for a trait is compared in MZ and DZ twins. The greater the difference in concordance between MZ and DZ, the greater the ______________

Answer 20

heritability

Question 21

1) What are the pros of these studies?
2) What are the limitations?

Answer 21

1) Familial aggregation studies, analysis of disease concordance in twins, and estimates of heritability
2) Tell us if there is a genetic component to a multifactorial disease, do not tell us which genes or how many genes