Autosomal inheritance

Question 1

Define phenotype

Answer 1

observed properties (different levels such as physical or cellular phenotype) of an individual as determined by genotype and environment.

properties can be based on the genotype as well as the environment

Question 2

Define autosomal dominant (AD), autosomal recessive(AR), and codominant phenotypes

Answer 2

AD=> phenotype present in the heterozygote

AR=>phenotype not apparent in the heterozygote

Codominant=>both alleles expressed in the heterozygote

Question 3

Track segregation of alleles through a pedigree and be able to relate genotypes to phenotypes

Answer 3

AD=> -often seen in multiple generations of a family and affects both sexes and transmitted by either sex
-each offspring of an individual has a 50% chance to be affected

AR=>on avg, 2 carrier parents: 25% affected offspring, 25% homozygous normal offspring, 50% heterozygous carrier offspring

• parents of an affected individual are obligate carriers and often normal
• mutations are transmitted through many generations of heterozygous carriers and may be present in only one sibship

Question 4

If a person has the genotype for sickle cell disease, but does not show the phenotype outwardly, how else will the phenotype be present?

Answer 4

-cellular level

Question 5

When looking at the heterozygote (Aa), and there is no phenotype presence of the A then what type of trait is it?

Answer 5

-AR

Question 6

If a patient has a genotype of aa but is normal phenotypically, what type of trait is it?

Answer 6

-AD

Question 7

If a patient has an autosomal dominant genotype, how many dominant alleles must be present for the patient to have the disease?

Answer 7

-1 allele

Question 8

Why do most autosomal dominant diseases rarely have 2 dominant alleles so you should assume the person is heterozygous for the condition (Aa)?

Answer 8

-most conditions the homozygous mutant is lethal

Question 9

Which trait, AD or AR, has the most number of heterozygous non-affected carriers?

Answer 9

-AR

Question 10

What could a loss of function mutation cause?

(Three things)

Answer 10

Loss of function mutations are common

• terminates the protein (nonsense)
• interfere with folding, unstable, degraded
• protein produced but active site or confirmational change occurs then it is a loss of function

Question 11

What is a gain of function mutation?

Answer 11

mutation causes protein to be expressed to lose control to cause over expression or expressed in the wrong tissues

Question 12

What is a dominant negative mutation in collagen cause?

Answer 12

osteogenesis imperfecta due to collagen disruption

Question 13

What is haploinsuffiency?

Answer 13

-half is not enough so if there is an autosomal dominant gene present then it will still cause the disease

Question 14

Which trait, AD or AR, is characteristic of male-male transmission which helps distinguish the disorder from X-linked disorders?

Answer 14

AD

Question 15

T/F Reduced penetrance and variable expressivity occur frequently in AD disorders

Answer 15

True

Question 16

In an AR disease, what is the % of an unaffected sibling of an affected individual to be a carrier?

Answer 16

-67%

Question 17

Loss of function and clinical phenotypes:
At 50% of residual function, you have a correspondance to heterozygote with 1 normal and 1 nonfunctional allele, so with this information, describe what A, B, C, D will have with respect to the mutation at the given area.

Answer 17

• A will be simple recessive with normal phenotype in heterozygote
• B will be autosomal dominant; haploinsuffiency
• C recessive with disease severity dependent of residual funciton
• D recessive with varying organ involvement

Question 18

What percentage of genes are shared in a 1st degree relative?

Answer 18

-50% (1/2)

Question 19

What percentage of genes are shared in a 2nd degree relative?

Answer 19

-25% (1/4)

Question 20

What percentage of genes are shared in a 3rd degree relative?

Answer 20

-12.5% (1/8)

Question 21

The proportion of shared genes is reduced by what factor when there is one common ancestor rather than 2?

Answer 21

-50% or 1/2

Question 22

How many meiosis are 2 ppl separated from in 2nd degree relative?

Answer 22

2

Question 23

Half siblings share what percentage of their genes?

Answer 23

-25% or 1/4

Question 24

In an autosomal recessive trait, where there is 2 parent carriers (Dd), what is the recurrence risk to the fetus to have the trait?

Answer 24

-25% (1/4)= .5x.5

Question 25

In an autosomal recessive trait, where there is 2 parent carriers (Dd), their son is healthy and does not show the disease so what is the probability he is a carrier?

Answer 25

-67% (1/3)

Question 26

In the hardy-weinberg principle, there is a math relationship relating genotype freq. and allele freq., what are the 2 assumptions?

Answer 26

• large population with random mating
• genotype freq

Question 27

Hardy weinberg principle at a population level, what is the equation?

Answer 27

Question 28

Hardy weinberg principle at a population level, describe the punnet square.

Answer 28

Question 29

For a locus with 2 alleles where p=0.99. What is the % for a heterozygous offspring?

Answer 29

-2%

Question 30

The hardy-weinberg equation has a clinical relevance, what is it?

Answer 30

-estimate carrier frequencies and disease incidence in autosomal recessive diseases

Question 31

If the allele frequency for Tay-Sach’s mutations is 1/50, what is the incidence of affected children? What is the proportion of carriers in the population?

Answer 31

-q=1/50

-2pq=1/25

Question 32

A disease has an incidence of 1 in 40,000 in a population. What is the carrier frequency?

Answer 32

-q^2 = 1/40,000 so q is equal to 1/200

Question 33

For 3 possible alleles, what is the Hardy-Weinberg equation?

Question 34

17. T/F For any heterozygote class in a population, genotype freq. = (2) x (allele 1 frequency) x (allele 2 frequency)

Answer 34

True