Population Genetics

Question 1

What is polymorphic?

Answer 1

When an allele is present in more than 1% of the population

Question 2

What are highly polymorphic genes? What is an example?

Answer 2

Determine individual characteristics and predicts that diversity of function is important

HLA genes provide variations of immune response in population

Question 3

What is a polymorphism where there is a difference of one nucleotide?

Answer 3

Single Nucleotide Polymorphism (SNP)

Question 4

What are non-polymorphic genes? What is an example?

Answer 4

Predicts that gene function has been optimized and that any change reduces function

Histone gene sequences are an example and they code for protein with essential cellular functions. Gene sequence is highly conserved across species

Question 5

Why is it important to have a high degree of polymorphism in a population?

Answer 5

Allows for quick adaptation to changing environmental conditions

Question 6

What are 3 facts about humans that genetic research on populations has revealed?

Answer 6

6 million single nucleotide polymorphisms between unrelated individuals

SNPs are normal genetic variation, they usually do not cause disease

3 deleterious recessive mutations per individual

Question 7

What is the Hardy-Weinberg model?

Answer 7

A model for the distribution of alleles in populations

The model predicts that allele frequencies in a population will not change over time

Question 8

What are the 5 assumptions of Hardy-Weinberg model?

Answer 8

1. Population is large
2. No new mutations
3. All genotypes have same fitness
4. Mating is random
5. No influx or efflux of alleles

Question 9

Are real populations ideal?

Answer 9

There are no ideal populations

Allele frequencies do change over time

Question 10

What disrupts the equilibrium of an ideal population?

Answer 10

Genetic drift - population is small

New mutations

Selection - unequal fitness

Assortative matine - nonrandom

Population bottlenecks and founder effect

Question 11

What do the Hardy-Weinberg equations describe?

Answer 11

Allele frequencies in the gene pool of a population

Genotype frequencies in populations

*Equations only work in ideal populations but are useful to calculate frequencies and can be used to detect deviations from predicted values

Question 12

What are the assumptions of the Hardy-Weinberg equations?

Answer 12

Assume that there are wild type and mutant alleles, p and q, and that they are both alleles of the same gene

p+q = 1 and p = 1 - q

Genotypes add up to 1 –> p^2 + q^2 + 2pq = 1

Question 13

What are the three possible genotypes?

Answer 13

pp - normal

pq - heterozygous

qq - homozygous mutant

Question 14

How do we apply the Hardy-Weinberg equations to the gene pool and people?

Answer 14

The gene pool contains wildtype and mutant alleles

Genotypes determined by random draws from gene pool

People can get 0, 1, or 2 mutant alleles

Probabilities for each of these are calculated based on frequencies of mutant alleles q in gene pool

Question 15

If 10% of alleles are mutant, what is the probability of drawing two mutant alleles in two draws?

Answer 15

q = 0.1

0.1 * 0.1 = 0.01 or 1%

Question 16

If the frequency of PAH mutant allele in gene pool is 1/120, what is the homozygote frequency?

Answer 16

(1/120)^2 = 0.7/10,000

Question 17

With a recessive disorder, what is the homozygote frequency when solving problems?

Answer 17

The homozygote frequency is the prevalence of the disorder or people affected with the disorder (q^2)

Question 18

What is the equation for finding heterozygote frequency? What can it be simplified to when the mutant allele frequency is low?

Answer 18

Heterozygote = 2pq

It is the change of getting just one mutant allele.

When mutant allele frequency, q, is low, the WT allele frequency (1-q) is close to one and so the Heterozygote equation = 2q

Question 19

How can the frequency of the mutant alleles in a gene pool be calculated?

Answer 19

Can be calculated based on the frequency of the disease

In recessive disorders, an affected individual is homozygous for the mutant allele

The probability to be homozygous is q^2

In recessive disorder, the frequency if the mutant alleles in the gene pool is thus square root (frequency of disease in population)

Question 20

Example problem. A patient wants to know how high the probability that he is a carrier of cystic fibrosis? CF affects 1/2000

Answer 20

1/2000 is the homozygote frequency

Allele frequency (q) in pool is then square root (1/2000) which equals 0.022 (2.2%)

Expected heterozygote frequency is 2pq = 4.3%

Question 21

How can you calculate allele frequency for dominant diseases?

Answer 21

In dominant disorders, virtually all affected people are heterozygous

Remember that in rare diseases, heterozygote frequency is roughly 2q

Allele frequency is then 1/2 * fraction of affected people

Question 22

How do you calculate allele frequency for X-linked recessive disorders?

Answer 22

Allele frequency equals fraction of affected males

So, 1% affected males = 1% defective alleles

Question 23

Summarize the Hardy-Weinberg equations?

Answer 23

Gene pool:
Mutant allele = q
WT allele = 1-q

Homozygous = q^2, affected with recessive disease

Heterozygous = 2pq, carriers of recessive disease or affected with dominant disease

Hemizygous = q, males affected with X-linked traits

Question 24

In real populations, how does the homozygote frequency deviate from predictions?

Answer 24

Assortative mating (not limited to consanguinity) increases homozygous frequency

Low fitness decreases homozygote frequency

Question 25

In real populations, how does the gene pool change over time?

Answer 25

Selection - unequal fitness

Population bottlenecks and founder effect

New mutations

Genetic drift - small populations

Question 26

What are the effects of selection?

Answer 26

Selection reduces the frequencies of alleles that reduce fitness

Dominant mutant alleles disappear quickly, but are constantly regenerated by new mutations

Recessive alleles disappear very slowly through selection - most recessive alleles are found in heterozygotes so there is no selective pressure on heterozygotes

Question 27

What is positive selection?

Answer 27

Heterozygotes often have an advantage because they can have a wider spectrum of enzyme activity or disease resistance

Some alleles provide advantage only in heterozygous state - alleles will cause disease in homozygous state

Some events select positively for heterozygotes

Question 28

What are hypothesized examples of some events that select positively for heterozygotes?

Answer 28

Some mutated genes cause disease in homozygous state and protect against certain diseases in heterozygotes

Typhoid fever, cholera, tuberculosis select for CFTR mutations

Malaria selects for Beta-hemoglobin mutations

Plaque selects for HFE mutations

Question 29

What is the founder effect?

Answer 29

When a new population is established by a small group of individuals from a larger population and carries a fraction of the genetic diversity of the population they came from

Question 30

What is an example of the founder effect?

Answer 30

Ellis-Van Creveld Syndrome

Prominent among Pennsylvania Amish

Mutation can be traced to founder in 18th century

Carrier frequency among Amish is 12.3% compared to general population which is 0.8%

Parental consanguinity in 30% of cases

Question 31

Is race or ancestry more relevant for placing the individual into the appropriate population risk group?

Answer 31

90% of genetic variation is between individuals - not between populations

Only 10% of variation is specific to ancestry

Ancestry is not a perfect predictor of drug response but often was the only one available

Need genome wide association studies to find meaningful variation

Question 32

What are some common disease and what populations are they most common in?

Answer 32

Cystic fibrosis most common in Caucasian population

Sickle cell anemia is most common in Sub-Saharan Africa

Glucose-6-Phosphate Dehydrogenase Deficiency is most common in African American males

Question 33

What is important to understand about genetic disorders being common in some populations?

Answer 33

Genetic disorders are not exclusive to certain populations and different populations might have different mutant alleles

Ancestral gene pool does not fully explain health disparities