Multifactorial Inheritance

Question 0

What factors may interact to create complex traits?

Answer 0

Variants in multiple genes and non-genetic factors may interact.

Question 1

Two basic characteristics of complex traits.

Answer 1

Aggregate (cluster) in families

Do not follow single Mendelian mode of inheritance

Question 2

What is the relationship between complex traits and genetic variants at the population level?

Answer 2

There is no simple relationship between genetic variant and trait when looking at the population.

Question 3

What three sorts of study designs are used to estimate the degree to which genetic variation is responsible for the observed variation in disease incidence?

Answer 3

Twin, adoption, and immigration studies

Question 4

What two factors must be distinguished in complex trait studies?

Answer 4

Genetic factors

Environmental factors

Question 5

How are monozygous vs dizygous twin studies used to show the relative contribution of genetic variation on a trait?

Answer 5

Assuming that the MZ and DZ twins shared equally similar non-inherited factors, a higher Concordance Rate for diseases in MZ twins suggests that genetic variation contributes more to the risk than non-inherited factors.

Question 6

What is the heritability of a trait?

Answer 6

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

Question 7

What does an allele or environment need in order to explain variability in a trait?

Answer 7

The allele or environment itself must demonstrate variability. If it doesn’t vary, it can’t cause variation in the trait.

Question 8

Does high heritability imply that non-genetic factors are unimportant?

Answer 8

No. Heritability is independent of environmental (non-genetic) factors. PKU is a highly heritable disorder, but there must also be phenylalanine in the diet for the disease to occur.

Question 9

How does studying monozygotic twins raised separately help determine the heritability of a disease?

Answer 9

If MZ twins develop the same disease in two different environments, that points to a strong genetic factor in the disease.

Question 10

How do adoption studies demonstrate genetic or non-genetic factors?

Answer 10

Unrelated siblings raised together show a 100% environmental factor and 0% genetic.
Related siblings raised separately show a 50% genetic factor and 0% environment.

Question 11

How do you calculate the risk of disease in relatives of a patient?

Answer 11

Lambda = (risk of disease in siblings of affected)/(risk of disease in general population)

Question 12

What is penetrance?

Answer 12

Penetrance describes the relationship between the gene and the trait. The penetrance of a genotype is the probability that and individual will develop the trait if they have the genotype.

Question 13

What is incomplete penetrance and how is it associated with complex diseases?

Answer 13

Incomplete penetrance means that some individuals with the genotype will not get develop the disorder. Genotype for complex disorders are generally thought to have low penetrance, thus their development is difficult to trace and predict.

Question 14

Name one disorder that shows incomplete penetrance.

Answer 14

Type 1 diabetes.

20% of the general population carries at least one of the two highest risk haplotypes, but only 4% develop the disease.

Question 15

What is variable expressively?

Answer 15

No two individuals with the same genetic variant express exactly the same disorder.

Question 16

What is Maturity Onset Diabetes in the Young?

Answer 16

A diabetic condition closely related to Type 1 diabetes which displays variable expressivity. Individuals with identical variants develop the disorder at widely varying times in life.

Question 17

What is allelic heterogeneity?

Answer 17

Review this subject and edit this card

Question 18

What is locus heterogeneity?

Answer 18

Differences in genes at different loci produce an identical trait or disorder.

Question 19

What characteristic of complex traits does early onset Alzheimer’s display?

Answer 19

It displays locus heterogeneity. Differences in genes at three separate loci may result in the same clinical disorder.

Question 20

What are phenocopies?

Answer 20

A disease or trait that mimics a genetic disorder but actually results from factors that are not primarily genetic. Thalidomide-induced limb malformation mimics a genetically induced defect, but results from an environmental factor (thalidomide)

Question 21

Four pieces of evidence that demonstrate a genetic component in Type 2 diabetes.

Answer 21

Type 2 aggregates in families
Concordance rates for MZ twins ~ twice that of DZ twins (35%-100%)
Risk to 1st degree relatives of affected ~3-4 times general population
Intermediate traits of blood glucose and insulin levels approx 50% heritable

Question 22

Because many simple Mendelian traits have characteristics of complex traits, what factor distinguishes them as “simple Mendelian”?

Answer 22

They have one major gene with high penetrance.

Question 23

What two factors converge to cause impaired glucose tolerance leading to Type II diabetes?

Answer 23

Insulin resistance

Insulin deficiency