Multifactorial Inheritance

Question 1

Multifactorial inheritance is indicated when there is

Answer 1

an increased risk to relatives, but there is no consistent pattern of inheritance within families.

Question 2

Simple Mendelian diseases are generally _______-gene disorders characterized by inheritance patterns that follow _______ expectations and are discernable by examining _______

Answer 2

single
Mendelian
pedigrees with multiple affected individuals

Question 3

Complex traits

Answer 3

• Aggregate (cluster) in families
• Do not follow simple Mendelian mode of inheritance
• Likely due to variants in multiple genes and non-genetic factors that may interact
• No simple relationship between genetic variant and trait when looking at the population

Question 4

Determining the Relative Contribution of Genetic and Environmental Variation

Answer 4

• Need to distinguish between clustering in families due to genetic factors and those due to shared environmental factors
• Twin, adoption, and immigration studies used
• Each measure of genetic contribution needs to be interpreted carefully, but as a group can provide compelling evidence for genetic contribution to trait.

Question 5

One problem in family studies is that individuals who are genetically related often share a similar

Answer 5

culture and environment

Question 6

Monozygous (MZ) twins are

Answer 6

identically matched for DNA sequence, age, and gender, and perhaps closely matched for environmental exposures

Question 7

Dizygous (DZ) twins

Answer 7

on average share 1/2 of their DNA sequences, but may be about as closely matched for other factors as are MZ twins

Question 8

If it can be assumed that MZ and DZ twins are equally similar with respect to non-inherited factors, then

Answer 8

twins can be used to get an estimate of the relative contribution of genetic vs. environmental variation to the trait

Question 9

A much higher concordance rate for disease in MZ than DZ twins suggests that

Answer 9

genetic variation contributes to variation in risk more than variation in non-genetic factors

Question 10

A much higher correlation among MZ compared to DZ twins for a quantitative trait suggests that

Answer 10

genetic variation is relatively more important than variation in non-genetic factors

Question 11

The Heritability of a trait is

Answer 11

the proportion of total variance in a trait that is due to variation in genes

Question 12

A high heritability implies

Answer 12

that differences among individuals with respect to a trait such as blood pressure in a population can be attributed to differences in the genetic make-up.

Question 13

The key to interpreting heritability estimates is to remember that

Answer 13

we’re talking about and describing variation in BOTH genetic factors AND non-genetic factors. If one (alleles or environment) doesn’t demonstrate much variability, then it doesn’t have much potential to explain variability in a trait

Question 14

Complex traits demonstrate one or more of the following

Answer 14

• Incomplete penetrance:
• Variable expressivity:
• Heterogeneity –
• Presence of phenocopies:

Question 15

Incomplete penetrance

Answer 15

not everyone with predisposing variant develops disease

Example: Type I diabetes and MHC

Question 16

Variable expressivity

Answer 16

no two individuals with the same genetic variant have exactly the same disease characteristics
Example: Maturity Onset Diabetes in the Young (MODY)

Question 17

Heterogeneity

Answer 17

allele and locus: The “same” disease can be caused by different alleles at one location or by alleles at different locations in the genome
Example (allele): Cystic Fibrosis
Example (locus): Alzheimer Disease

Question 18

Presence of phenocopies

Answer 18

Individuals who have the disease or trait for reasons that are not primarily genetic even though clinical presentation mimics the more genetic version
Example: Thalidomide-induced limb malformation vs. genetically-induced

Question 19

Implications of Characteristics of Complex Traits

Answer 19

it is very difficult to predict whether or not individuals will develop a certain complex disease or trait, even when you may know something about their family history or their alleles at a certain locus, and it is difficult to identify the genetic variants that might contribute to disease