Inheritance of Complex Disorders

Question 1

Complex diseases or traits

Answer 1

• Results from complex interactions between genes and environment
• Runs in families, but does not fit single gene Mendelian
• Often exhibits reduced penetrance, variable expressivity, heterogeneity, phenocopies, etc
• Often common and of smaller effect, so they survive selection
• Often uses empirical risk values for counseling

Question 2

Differentiating between reduced penetrance and variable expressivity

Answer 2

Reduce dpenetrance - NO clinical symptoms

Variable expressivity - Varying degrees of severity, or different clinical expression entirely

Question 3

Phenocopies

Answer 3

Environmental causes that look familial.

Ex) Maternal use of accutane can cauase babies to look like they have DeGeorge syndrome

Question 4

4 known genes are known to cause Alzheimer’s. What is this an example?

Answer 4

Heterogeneity

Question 5

Age-dependent penetrance

Answer 5

Younger siblings may not yet express phenotype

Question 6

Modifying genes

Answer 6

Gene-gene interactions; many genes of small effect can modify the phenotype of a single major gene

Question 7

Genotype-environment interaction

Answer 7

Dfiferences in genotypes with respect to risk factor variability OR genotype/risk association depends on environmental factors.

Ex) Fauvism- don’t havenay problems until you eat fava beans

Question 8

Pleiotrophy

Answer 8

A single locus affects several traits

Question 9

Polygeneic trait

Answer 9

is determined by many genes of small and equal and additive effects, so many loci are involved.

Assumed to be completely genetic

Question 10

Multifactorial inheritance

Answer 10

A mixture of many genes of small effect act together with environmental risk factors

Question 11

Threshold model

Answer 11

Distribution of liability fo ra trait/disease determined by both genes and environment.

At a certain threshold (which varies depending on sex), the person is affected

Question 12

In multifactorial inheritance- For a quantitative trait, the mean value for offspring is

Answer 12

halfway between the mean value of the parents and that of the generla population

Question 13

Multifactorial inheritance - when occurrence differs based on sex, the reucrrence risk is highger for

Answer 13

relatives of the patient of hte less susceptible sex

Question 14

True/false: Consanguinity poses greater likelihood of occurrence or recurrence in multifactorial inheritance

Answer 14

true

Question 15

In multifactorial inheritance, the reucrrence risk is higher when __ or __

Answer 15

multipel family members are affected

the disorder is more severe in expression

Question 16

In multifactorial inheritance, correlation between relatives is proportional to

Answer 16

genes in common

(the more closely related, the higher frq)

Question 17

Correlation coefficient for quantitative traits

Concordance rates for qualitiatve traits

Answer 17

Estimates relative contribution of underlying genetic components

Question 18

Heritability

Answer 18

Proporiton of total phenotypic variation that is due to genetics IN THE POPULATION

Note: population statistics can’t infer anything about an individual!

Question 19

Relative risk of disease

Answer 19

Comparing the risk to a specific relative type to the risk in the general population

Question 20

Mosaicism

Answer 20

Two cell lines of different genotype or karyotype, derived form a single zygote.

Results form a new mutaiton ina precursor cell ro during tissue differentiation - so you can have mosaicism within a cell type or between cell types.

Question 21

Genomic imprinting

Answer 21

Modification of geneti cmaterial that takes place depending on whether the genetic info is dervied from the mother or father

Question 22

Prader Willi and Angelman syndrome are examples of

Answer 22

Genomic imprinting

Question 23

Age of onset depends on whether or not teh huntingtons gene was transmitted from dad or mom. This is an example of

Answer 23

genomic imprinting

Question 24

Trinucleotide repeat regions

Answer 24

ARe unstable and during reproduction, tend to increase –> gene abnormality and disease expression

Fragile X, Huntingtons, Myotonic dystrophy

Question 25

Anticipation

Answer 25

Increase in severity or earlier age of onset of a disorder in scucessive generations.

Question 26

In huntingtons, the trinucleotide repeats become greatly increased in transmitted through a male and result in earlier age of onset

Answer 26

Anticipation, trinucleotide repeats, and genomic imprinting

Question 27

Quantitative vs Qualitative traits

Answer 27

Quantitative traits: presence or absence of disease. Ex) You have htn if you’re above this cutoff point

Qualitative traits: continuous variation in phenotype

Question 28

If the correlation among MZ twins is higher than that among DZ twins, then

Answer 28

There is a genetic component for the disease, but unless the correlation for MZ twins is 1.0, then environment is also at play

Question 29

A disease involves 3 loci.

The highest frq of the disease is seen at 3-4 upper case alleles, and teh lowest frq is seen at 0 or 6 upper-case alleles.

What is this an example of?

Answer 29

Polygenic inheritance: large # of loci contribute equal and additive effects; BELL CURVE

Ex) eye color genes