Population Genetics Flashcards
What is polymorphic?
When an allele is present in more than 1% of the population
What are highly polymorphic genes? What is an example?
Determine individual characteristics and predicts that diversity of function is important
HLA genes provide variations of immune response in population
What is a polymorphism where there is a difference of one nucleotide?
Single Nucleotide Polymorphism (SNP)
What are non-polymorphic genes? What is an example?
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
Why is it important to have a high degree of polymorphism in a population?
Allows for quick adaptation to changing environmental conditions
What are 3 facts about humans that genetic research on populations has revealed?
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
What is the Hardy-Weinberg model?
A model for the distribution of alleles in populations
The model predicts that allele frequencies in a population will not change over time
What are the 5 assumptions of Hardy-Weinberg model?
- Population is large
- No new mutations
- All genotypes have same fitness
- Mating is random
- No influx or efflux of alleles
Are real populations ideal?
There are no ideal populations
Allele frequencies do change over time
What disrupts the equilibrium of an ideal population?
Genetic drift - population is small
New mutations
Selection - unequal fitness
Assortative matine - nonrandom
Population bottlenecks and founder effect
What do the Hardy-Weinberg equations describe?
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
What are the assumptions of the Hardy-Weinberg equations?
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
What are the three possible genotypes?
pp - normal
pq - heterozygous
qq - homozygous mutant
How do we apply the Hardy-Weinberg equations to the gene pool and people?
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
If 10% of alleles are mutant, what is the probability of drawing two mutant alleles in two draws?
q = 0.1
0.1 * 0.1 = 0.01 or 1%
If the frequency of PAH mutant allele in gene pool is 1/120, what is the homozygote frequency?
(1/120)^2 = 0.7/10,000
With a recessive disorder, what is the homozygote frequency when solving problems?
The homozygote frequency is the prevalence of the disorder or people affected with the disorder (q^2)
What is the equation for finding heterozygote frequency? What can it be simplified to when the mutant allele frequency is low?
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
How can the frequency of the mutant alleles in a gene pool be calculated?
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)
Example problem. A patient wants to know how high the probability that he is a carrier of cystic fibrosis? CF affects 1/2000
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%
How can you calculate allele frequency for dominant diseases?
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
How do you calculate allele frequency for X-linked recessive disorders?
Allele frequency equals fraction of affected males
So, 1% affected males = 1% defective alleles
Summarize the Hardy-Weinberg equations?
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
In real populations, how does the homozygote frequency deviate from predictions?
Assortative mating (not limited to consanguinity) increases homozygous frequency
Low fitness decreases homozygote frequency
In real populations, how does the gene pool change over time?
Selection - unequal fitness
Population bottlenecks and founder effect
New mutations
Genetic drift - small populations
What are the effects of selection?
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
What is positive selection?
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
What are hypothesized examples of some events that select positively for heterozygotes?
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
What is the founder effect?
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
What is an example of the founder effect?
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
Is race or ancestry more relevant for placing the individual into the appropriate population risk group?
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
What are some common disease and what populations are they most common in?
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
What is important to understand about genetic disorders being common in some populations?
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
