19.04.01 Population genetics definitions

Question 1

Definition of allele frequency

Answer 1

• Proportion of an allele (or variant) among all allele copies at a given locus.
• Given as a percentage
• Used to estimate genetic diversity at an individual, population or species level

Question 2

Definition of association study

Answer 2

• Statistical method for estimating the co-occurrence of genetic alleles with a phenotype
• association = allele occurs more with phenotype than would be expected by chance

Question 3

Difference between association study and linkage study?

Answer 3

• Linkage requires families with multiple affected individuals, looks at linked microsatellites/SNPs which can be 20 million bp apart and identifies variants of large effects (but normally requires multiple affected families with variants in the same gene to detect)
• Association studies use a series of unrelated case/control studies to get significance, tests over a million SNPs which are in linkage disequilibrium and require a common haplotype.

Question 4

Epistasis

Answer 4

The effect of one gene being dependent on the presence of one or more ‘modifer’ genes

Question 5

Fitness

Answer 5

Probability of survival and reproduction in a particular environment

Question 6

Gene flow

Answer 6

Flow of genetic material between previously separate populations (caused by migration and mating)

Question 7

Gene pool

Answer 7

Collection of all of the alleles of all of the genes within a freely interbreeding population

Question 8

Genetic drift

Answer 8

A change in allele freq in a population over time due to chance (not driven by adaptive pressures).
Can result in loss of some alleles, and can have a significant effect when a population suddenly decreases in numbers (i.e. after a natural disaster).

Question 9

Genetic hitchhiking

Answer 9

When an allele changes freq because another allele which it is in LD with is under selection pressures.

Question 10

Genetics linkage

Answer 10

Tendency for gens close to each other to be inherited together during meiosis
The greater the distance between the two genes, the greater the chance of recombination between sister chromatids

Question 11

Genetic screening programmes

Answer 11

• early detection or exclusion of a genetic disease
• detects predisposition or resistance to disease
• determines whether a person carries a variant

Question 12

Genotype freq

Answer 12

Percentage of people with that genotype

Question 13

Genome wide association studies (GWAS)

Answer 13

Look for association between genes and phenotypes at a genome wide level. Normally have only detected common genes which have modest effects and only account for some of the the disease susceptibility

Question 14

Haplotype

Answer 14

Representation of linked alleles in a cluster of related genes

Question 15

Hardy-Weinberg equilibrium

Answer 15

Freq of alleles remain constant through generations in the absence of evolutionary forces (so no natural selection, no mutations, no genetic drift etc)

Question 16

Linkage disequilibrium (LD)

Answer 16

Non-random distribution of adjacent alleles into gametes. Some combination of alleles occur more or less often than chance

Question 17

Minor allele freq

Answer 17

Freq of least common alelle

Question 18

Mutation rate

Answer 18

Rate of gene changes from WT to mutation. Normally expressed as number of mutations per unit, i.e. number f mutations per cell division

Question 19

Natural selection

Answer 19

Individuals within a population who are the fittest for the environment they are in, as they have the best combination of alleles.

Question 20

Odds ratio

Answer 20

The odds of having the disease and the risk allele, compared to only having the disease (and no risk alleles). The higher the OR the greater the effect on phenotype

Question 21

Penetrance

Answer 21

Proportion of individuals carrying a particular allele and having the associated phenotype

Question 22

Recombination freq

Answer 22

Proportion of recombinant offspring produced in a genetic cross between two organisms

Question 23

Relative risk

Answer 23

Probability of having the disease when the patient has the at risk allele in an association study

Question 24

SNP

Answer 24

Variation in DNA sequence in which a single nucleotide is replaced by another base. Useful marker in linkage studies. Very prevalent - nearly 10 million in genome