Lecture 29

Question 1

Define heritability

Answer 1

Proportion of the total phenotypic variation that is due to genetic difference for a particular population in a given environment

Question 2

What are the limitations of heritability?

Answer 2

Does not indicate the degree to which a characteristic is genetically determined; an individual does not have heritability; indicates nothing about the nature of population differences in a characteristic

Question 3

What is the significance of quantitative trait loci (QTLs)?

Answer 3

Mapped by identifying molecular markers that correlate (segregate with) an observed trait; often an early first step in identifying and sequencing the actual genes that cause the trait variation

Question 4

Examples of complex diseases

Answer 4

Diabetes (insulin/non-insulin dependent), alzheimer’s, asthma, rheumatoid arthritis, hypertension, schizophrenia

Question 5

What is segregation analysis?

Answer 5

Choice of families affects results; multiple genes analyzed together

Question 6

What is association analysis?

Answer 6

Small areas of genome examined, larger areas lead to false positives

Question 7

Environmental influences on the following diseases:

Type 2 diabetes, Hypertension, Obesity, Alzheimer’s, Cancer, Schizophrenia

Answer 7

Type 2 Diabetes: diet, obesity, lifestyle
Hypertension: diet, obesity, lifestyle
Obesity: diet, lifestyle
Alzheimer’s: head trauma, aluminum exposure, vascular disease
Cancer: lifestyle, diet
Schizophrenia: possibly developmental issues?

Question 8

Characteristics of Alzheimer’s disease

Answer 8

Most common form of senile dementia, neurons lost in cerebral cortex and hippocampus, 2 formations in brain are characteristic (neurofibrillary tangles/tau proteins and amyloid plaques)

Question 9

What is the genetics of the autosomal dominant form of Alzheimer’s?

Answer 9

Mutations in APP (A-beta peptide precursor); greater aggregation and greater production of A-beta 42

Mutations in presinilin I (part of gamma-secretase); most cases of familial AD are attributable to completely penetrant missense mutations in this subunit

Question 10

What is the concordance of AD in mono/di-zygotic twins?

Answer 10

80% MZ, 35% DZ; suggests that AD is familial or that there is a genetic influence, but difficult to separate genetics from shared environmental influences

Question 11

What is the function of APOE and what percent have the APOE-epsilon4 allele?

Answer 11

Cholesterol transport; found in plaques and tangles; 25-35% have allele