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Flashcards in Population Genetics Deck (34):

Population Genetics

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


Four main evolutionary forces effecting allele frequency

natural selection
genetic drift
gene flow


How is population health used by scientists

use to predict allele (or disease) changes in populations


How is population genetics used by clinicians

Predict risk for individuals


Why is population genetics important?

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


How can we estimate allele frequency in a population?

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)



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



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


Founder Effect

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


Genetic drift

Random fluctuations of allele frequencies, usually over small populations



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


Fitness measures what?

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


Selection depends on what?



When does natural selection occur?

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


What is the consequence of migration / gene flow?

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


Fitness is measured how?

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


Coefficient of selection

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


Mutation rate?

The frequency of new mutation at given locus

Measured as mutations/generation


Mutation rates for autosomal dominant: Direct method

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


Mutation rate for autosomal dominant: Indirect method

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


What is the major utility of Hardy Weinberg in medicine?

Genetic counseling for autosomal recessive


Idealized assumptions of Hardy Weinberg

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


Three types of non random mating that could occur?

Assortive mating



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


Assortive mating

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.)



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.


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

Social stratification


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

Assortive mating


Do new mutations occur frequently?

Yes, new mutations are a regular occurance


Do most mutations cause disease?

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


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

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


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

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


What is the utility of Hardy Weinberg?

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


Areas to focus on (3)

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