multifactorial inheritance

Question 1

simple medelian trait

Answer 1

genetic variant leads to a trait

Question 2

variable disease progression depends on

Answer 2

other factors besides just genetic variant

different alleles in the same gene associated with varying severity

Question 3

complex traits explain

Answer 3

multifactoial ineritance.

Many things lead to trait

Question 4

examples of multifactorial inheritance

Answer 4

1. cancer
2. type 1/2 diabetes
3. alzheimers
4. IBD
5. schizophrenia
6. cleft lip/palate
7. hypertension
8. asthma

Question 5

complex traits/Multifactorial inheritance

Answer 5

1. complex trait aggregates in family
2. do not follow simple mendelian mode of inheritance
3. need to distinguish between clustering in families due to genetic facts and those due to shared environmental facts.
4. epidemiologic twin, adoption and immigration studies used
5. each measure of genetic contribution need to be interpreted carefully, but as the group can provide compelling evidence fro genetic contribution to trait

Question 6

twin studies: mono vs. dizygotic

Answer 6

mono: share 100% DNA
certain amount of environment

di: share 50% of DNA certain amount of environment

Question 7

if twins raised together and assume same degree of similar environment, then difference in concordance rate between mono and di likely due to

Answer 7

genetic factors

Question 8

If twins raised apart and assume had different environments then similarities in trait are likely due to

Answer 8

genetic factors

Question 9

adoption studies

Answer 9

compare similarity btwn biologic siblings raised apart and adoptive siblings

Question 10

If biological sib 2 more concordant with biological sibling than adopted sibling, then have evidence for _____ as opposed to _____

Answer 10

genetic component as opposed to environmental component

Question 11

risk of disease in relatives

Answer 11

risk of disease in siblings of affected/ risk of disease in general population

Question 12

heritability

Answer 12

h2

proportion of variance in trait that is due to genetic variation

Question 13

low heritability

Answer 13

less than 50%

Question 14

high heritability

Answer 14

more than 50%

Question 15

characteristics of complex traits

Answer 15

1. incomplete penetrance
2. variable epxressivity
3. heterogeneity –allele and locus
4. presence of phenocopies

Question 16

penetrance

Answer 16

relationship between trait and genotype

probability that an individual will develop the trait if they have the genotype

Question 17

complete penetrance

Answer 17

everyone with pre-disposing genotype will get the trait

Question 18

incomplete penetrance

Answer 18

some with genotype will not get the trait

Question 19

susceptibility variants for complex diseases are generally though to have ______

Answer 19

low penetrance

Question 20

example of incomplete penetrance

Answer 20

type 1 diabetes.

up to 20% of general population has two highest risk haplotypes, but incidence is only 0.4%

Question 21

variable expressivity

Answer 21

individuales with the same variant do not show precisely the same disease or quantitative phenotype characteristics
example age dependent diabetes

Question 22

allelic heterogeneity

Answer 22

1. different alleles in the same gene result in the same trait
2. different alleles in the same gene result in different traits
3. ex. cystic fibrosis
4. many allele appear to have a very similar clinical progression of the disease
5. allele can be grouped into classes; severity of lungs and pancreatic involvement depends on the allele class

Question 23

locus heterogeneity

Answer 23

1. variants in different genes result in very similar clinical presentation
2. early onset alzheimer disease
3. mutations on 3 different genes all result in identical clinical manifestations of early onset AD

Question 24

phenocopy

Answer 24

environmentally cause phenotype that mimics the genetic version of the trait

Question 25

example of phenocopy

Answer 25

thalidomide-induced limb malformation vs. genetically induced

Question 26

Concordance rates are often used to

Answer 26

compare MZ and DZ twins. A higher concordance rate for disease in MZ than DZ twins suggests that genetic variation contributes to variation in risk more than variation in non-genetic factors

Question 27

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

Answer 27

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

Question 28

The Heritability of a trait is the proportion of

Answer 28

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

Question 29

A high heritability implies

Answer 29

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 30

The key to interpreting heritability estimates is to remember that we’re talking about and describing

Answer 30

``` 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 31

Implication: A high heritability does not imply that

Answer 31

non-genetic factors are not important. A low heritability does not imply that environment is not important.

Question 32

incomplete penetrance example

Answer 32

Type 1 diabetes and MHC

Question 33

variable expressivity example

Answer 33

maturity onset diabetes i the young (MODY)

Question 34

Variable expressivity means that

Answer 34

no two individuals with the same genetic variant have exactly the same disease characteristics

Question 35

heterogeneity examples

Answer 35

cyctic fibrosis | alzheimers disease

Question 36

heterogeneity

Answer 36

allele and locus: The “same” disease can be caused by different alleles at one location or by alleles at different locations in the genome

Question 37

Presence of phenocopies:

Answer 37

Individuals who have the disease or trait for reasons that are not primarily genetic even though clinical presentation mimics the more genetic version

Question 38

examples of phenocopies

Answer 38

Thalidomide-induced limb malformation vs. genetically-induced

Question 39

it is very difficult to predict whether or not individuals will develop a certain complex disease or trait, even when

Answer 39

you may know something about their family history or their alleles at a certain locus. example: AD and APOE locus

Question 40

The role of non-genetic factors in contributing to variation in complex traits will

Answer 40

vary from trait to trait and individual to individual.