Population Genetics

Question 1

Population Genetics

Answer 1

The study of allele frequencies and changes in allele frequencies in populations

Question 2

Four main evolutionary forces effecting allele frequency

Answer 2

natural selection
genetic drift
mutation
gene flow

Question 3

How is population health used by scientists

Answer 3

use to predict allele (or disease) changes in populations

Question 4

How is population genetics used by clinicians

Answer 4

Predict risk for individuals

Question 5

Why is population genetics important?

Answer 5

It is important for understanding allele frequency in populations (an how those frequencies change)

Question 6

How can we estimate allele frequency in a population?

Answer 6

Population sampling by phenotype can lead to estimates of allele frequency if the underlying genetic mechanism is known (i.e. dominant vs. recessive // autosomal vs. sex-linked)

Question 7

Mutation

Answer 7

Any change in the nucleotide sequence and/or arrangement of DNA (as compared to some reference standard). Although some doctors use the word “mutation” to imply a disease-causing / pathogenic change, the technical definition does not require that the mutation lead to disease

Question 8

Polymorphism

Answer 8

a genetic variant (mutations) which is common (>1%) in the population

Question 9

Founder Effect

Answer 9

A high frequency of a mutant allele in a population founded by a small ancestral group when one or more of the original founders was a carrier of the mutant allele

Question 10

Genetic drift

Answer 10

Random fluctuations of allele frequencies, usually over small populations

Question 11

Selection

Answer 11

active selection of favorable alleles (confer fitness advantage) over unfavorable ones

Question 12

Fitness measures what?

Answer 12

Reproductive success - it is a measure of the chance an allele will be transmitted to the next generation

Question 13

Selection depends on what?

Answer 13

Fitness

Question 14

When does natural selection occur?

Answer 14

Generally only occurs when the trait is expressed, which means that even severe recessive alleles are not selected against in the heterozygous state. Exceptions would be if genetic testing makes someone decide not to risk having a child

Question 15

What is the consequence of migration / gene flow?

Answer 15

When populations with different allele frequencies for a disorder mix (typically seen in cases of immigration) then allele frequencies can change
e.g. CCR5

Question 16

Fitness is measured how?

Answer 16

On a scale from 0-1 with 1 being normal reproductive success and 0 being non-heritable (i.e. gene is not passed on)

Question 17

Coefficient of selection

Answer 17

Measure of forces reducing fitness
S = 1-F or
F = 1-S

Question 18

Mutation rate?

Answer 18

The frequency of new mutation at given locus

Measured as mutations/generation

Question 19

Mutation rates for autosomal dominant: Direct method

Answer 19

For autosomal dominant diseases with 100% penetrance, one can simply count the number of new cases that occur with no family history.
For example, if 12 disease cases are identified in 100,000 children and 10 of the 12 cases have a negative family history, then the mutation rate is 10/100,000 children -
Since each child has 2 alleles of each gene, the mutation rate would be 10/200,000

Question 20

Mutation rate for autosomal dominant: Indirect method

Answer 20

For autosomal dominant conditions where the reproductive fitness is zero (i,e, effected persons do not survive to reproduce and/or are infertile) then all cases represent new mutations. Since each child inherits 2 genes, then the incidence (I) of the disease is really twice the mutation rate –> I = 2u
or u = 1/2I

Question 21

What is the major utility of Hardy Weinberg in medicine?

Answer 21

Genetic counseling for autosomal recessive

Question 22

Idealized assumptions of Hardy Weinberg

Answer 22

Large population mating randomly
Allele frequencies remain constant over time because
No appreciable rate of new mutation
No selection for/against allele
No appreciable immigration/emigration

Question 23

Three types of non random mating that could occur?

Answer 23

Stratification
Assortive mating
Consanguinity

Question 24

Stratrification

Answer 24

refers to populations containing 2 ore more subgroups which tend to preferentially mate within their own subgroup - mate selection is not dependent on the trait/disease of interest

Question 25

Assortive mating

Answer 25

Refers to when the choice of mate is dependent (in part) on a particular trait (or sometimes a disease). This occurs because people tend to choose mates who resemble themselves (language, height, skin color, etc.)

Question 26

Consanguinity

Answer 26

Occurs when persons marry closely-related blood relatives. This, non-random mating practice increases mating between carriers of autosomal recessive diseases, thereby increasing the number of cases of autosomal recessive diseases in the population.

Question 27

African Americans have a higher rate of sickle cell anemia then would be predicted by HWE, what causes this?

Answer 27

Social stratification

Question 28

Dwarfs, blind, and deaf selecting to mate with each other would throw off HWE, this is an example of?

Answer 28

Assortive mating

Question 29

Do new mutations occur frequently?

Answer 29

Yes, new mutations are a regular occurance

Question 30

Do most mutations cause disease?

Answer 30

No, most new mutations are benign (not disease causing)

Question 31

How can we determine whether our estimates of mutation rates are accurate?

Answer 31

NextGen sequencing will determine whether the “estimates of mutation” turn out to be accurate

Question 32

How can we calculate the rates of mutation for different conditions?

Answer 32

By observing the number of cases of disease in a population, it is possible to calculate the rates of mutation for different conditions

Question 33

What is the utility of Hardy Weinberg?

Answer 33

It allows us to measure allele frequencies and use them to predict genotypes

p+q = 1
p^2 + 2pq + q^2 = 1

***Clinically useful for recessive conditions and carrier rates

Question 34

Areas to focus on (3)

Answer 34

HWE (what does it tell us and what are the assumptions)

How to calculate q and 2pq from prevalence data

Mutation rate calculations and AD disease based on new incident cases