Lecture 12&13 - Allele Frequency

Question 1

What is a population

Answer 1

Interbreeding groups of organisms (of the same species)

Question 2

Where does genetic variation come from

Answer 2

Mutation and recombination

Question 3

What is an allele

Answer 3

Alternative DNA sequences at a locus (version of a gene) inherited as a unit

Question 4

What is a locus

Answer 4

The position in the genome being considered

Question 5

Way is a single nucleotide polymorphism (SNPs)

Answer 5

variation at a single position in a DNA sequence among individuals

Question 6

What is genetic variation for a trait

Answer 6

Genetically based phenotypic differences between individuals arise
from sequence differences

Question 7

Why may a gene have no effect on traits

Answer 7

If all individuals have the same allele, the locus does not contribute variation
– i.e., the gene does not contribute to phenotypic differences between
individuals
– The nature of phenotypic variation contributed by a gene depends on the
nature of the allelic variants at the locus

Question 8

What produces genetically-based phenotypic variation

Answer 8

Genes with different alleles that lead to different phenotypes

Question 9

How is frequency of an allele calculated

Answer 9

Frequency of allele A = Number of A alleles/ Total number of alleles

Question 10

How is the number of alleles in a diploid population calculated

Answer 10

Total number of A alleles = 2x the number of AA homozygotes
(nAA) + the number of Aa heterozygotes (nAa)
(slide 13)

Question 11

Why do we care about change in allele frequencies

Answer 11

Evolution
Can be used to understand migration/gene flow
– Different alleles may be favoured in different environments
– Infer how some types of phenotype variation are associated with
genetic differences
* E.g., compare frequency of alleles at some loci in a group suffering from
a genetic disorder to a group that does not.

Question 12

What is a genotype frequency

Answer 12

Number of individuals with the genotype divided by total number of individuals

Question 13

How is genotype frequency (f) calculated

Answer 13

f (AA) = Number of AA individuals / Number of individuals§

Question 14

What is the Hardy-weinberg model

Answer 14

Two alleles in a diploid individual are randomly and independently
sampled from an infinitely large pool of gametes
Probability of sampling the A allele is p
Probability of sampling the a allele is (slide 20)

Question 15

What are some assumptions of the Hardy-weinberg model

Answer 15

Population is very large
Random mating
No migration in or out of the population
No selection
No mutation

Question 16

What does a large population mean for the H-W model

Answer 16

Eliminates sampling error
* You expect the frequency of A in your population to be p, but
it would not necessarily be p in a finite sample
* No sampling error means allele frequencies are constant
* Allows for mathematically simple model

Question 17

What does Random mating for the H-W model mean

Answer 17

All individuals have an equal chance of mating with each
other
* No assortative mating, no inbreeding, no outbreeding

Question 18

What does No migration in or out of the population for the H-W model mean

Answer 18

Closed population, no alleles entering leaving through
migration
* So, the allele frequencies are not influenced by
variation entering from other populations

Question 19

What does no selection mean for the H-W model

Answer 19

Alleles do not affect fitness, so survival and
reproduction are not associated with the genotype of
an individual
* So, genotype frequencies are not altered by differential
fitness
* And allele frequencies are not changing over time due
to differences in their ‘success’

Question 20

What does no mutation mean for the H-W model

Answer 20

Mutations do not ‘add’ or ‘subtract’ copies of an allele
from the population
* No new alleles are introduced

Question 21

What does the H-W model offer

Answer 21

Idealised reference
Reference point against which real population genetic data can be compared
Can be considered a null model

Question 22

What are the predictions of the H-W model

Answer 22

Prediction: the allele frequencies of a population do not change
solely due to random mating.

• Prediction: genotypic frequencies are the product of allele
  frequencies and will return to these frequencies after a single
  generation of random mating.

Question 23

What are the predicted genotype frequencies for the H-W model

Answer 23

Freq. homozygous A (AA)= p2
Freq. homozygous a (aa)= q2
Freq. heterozygote (Aa)= 2pq

Question 24

What is the main violation of the H-W assumptions

Answer 24

Non-random mating
Finite population
Natural selection

Question 25

What is the effect of non-random mating on the H-W model

Answer 25

Non-random mating affects genotype frequencies in a population - Some combinations of alleles will occur at higher frequency than expected, others at lower frequency

Question 26

What are the types of non-random mating

Answer 26

Assortive mating Disassortative mating Inbreeding

Question 27

What is assortative mating

Answer 27

genetically or phenotypically similar individuals tend to mate with each other

Question 28

What is negative assortative mating

Answer 28

genetically or phenotypically dissimilar individuals tend to mate with each other

Question 29

What is inbreeding

Answer 29

Individuals mating with relatives

Question 30

What is the affect of asssortative mating on H-W model

Answer 30

Phenotype-biased mating means frequencies of certain genotypes, in loci underlying the phenotype, will be altered * Can affect heterozygosity, increasing or decreasing it depending on the pattern * This effect is not genome-wide, though it can be multiple loci * Traits are generally shaped by multiple loci instead of one, more on this later

Question 31

What is the affect of inbreeding

Answer 31

Relatives share alleles, so offspring produced by matings between relatives are more likely to have two copies of the same allele * Can measure this by considering whether an individual has a pair of alleles that are identical by descent (IBD) * Inbreeding increases the likelihood of alleles being IBD * These individuals are homozygous so inbreeding increases homozygosity and reduces heterozygosity

Question 32

What is the effect of inbreeding on the H-W equation

Answer 32

F(AA) = p2 + pqF F(Aa) = 2pq − 2pqF F(aa) = q2 + pqF F = proportional reduction in the frequency of heterozygotes compared to that expected in the Hardy-Weinberg model

Question 33

What is inbreeding depression

Answer 33

Occurs when inbreeding leads to reduced viability and/or fecundity (‘fitness’) Must be caused by a general pattern of lower fitness of homozygotes compared to heterozygotes

Question 34

What is the most likely result of inbreeding and why

Answer 34

Deleterious recessive mutations Harmful genetic variants that cause negative effects only in homozygotes * Heterozygotes are “carriers” * Examples include lots of genetic diseases, e.g. cystic fibrosis Rare, hidden in heterozygotes, cannot be removed by selection

Question 35

Why do allele frequencies change

Answer 35

Genetic Drift Natural selection Migration

Question 36

What is genetic drift

Answer 36

Random changes in allele frequencies (slides 3-8 PPT 2)

Question 37

How does a finite population violate the H-W population

Answer 37

Randomly sample alleles from a ‘gamete pool’ to make the next generation of individuals * In a finite population, the frequencies of alleles you sample to create a population can (and will) differ from the actual frequencies in the gamete pool * For any allele frequency, the expected amount of ‘error’ is proportional to 1/2N (where 2N is the total number of alleles)

Question 38

What is a bottleneck

Answer 38

When populations go through drastic reductions in population size, it can produce huge ‘drift events’ (slides 9-11 ppt 2)

Question 39

What is a founder event

Answer 39

Similar to bottlenecks, when a new population is founded by very few individuals, the allele frequencies can be very different from the original population (slides 12-17 ppt 2)

Question 40

How does Natural selection violate H-W

Answer 40

Selection favours one allele Overdominance

Question 41

What is migration (gene flow)

Answer 41

Movement of alleles from one population to another

Question 42

How does migration violate H-W model

Answer 42

Isolated populations will tend to become more different from each other in allele frequencies over time - differences in local pattern of selection - differences caused by drift * Migration opposes this process and reduces genetic differences between populations, through exchange (slide 24-25 PPT 2)

Question 43

Reading:

Answer 43

Genetics: a conceptual approach Chapter 25 How life works chapter 20.1-20.5