Flashcards in Hollox Deck (76):
What is a population?
Group of interbreeding individuals in the same space at the same time.
What is genotype frequency?
Percentage of individuals with a particular allelic combination within the population.
What is allele frequency?
Percentage of copies of a particular variant of a gene.
What is heterozygosity?
Percentage of heterozygous genotype bearers within the population.
What is heterozigosity used for?
Measurement of variability of a gene/polymorphism.
What are the two equations derived from the Hardy-Weinberg model?
What are the assumptions made by the Hardy-Weinberg model?
Panmitic populations; No selection; No mutation; No migration; Infinite/very large population size; Allele frequencies identical in males and females.
How does migration reduce homozygosity?
By breaking the Wahlund Effect which increases homozygosity.
How is change in homozygosity calculated?
?H = ((p(1)^2+p(2)^2)/2) - p(ext)^2.
What is the Wahlund Effect?
Reduction of heterozygosity caused by structurisation of a population.
What effect does population size have on drift?
An individual with 10 offspring has a greater impact on allelic frequencies than an individual with 2 offspring. The effect difference decreases with increasing population size. Small populations more likely to drift quicker.
How can genetic drift be modeled?
Pick an allele at random. Copy and reintroduce into the population. Repeat 2N times.
What is the effect of habitat loss on genetics of a population?
Reduced size - Increased drift, Variation lost quicker.
How can the loss of variation be measured?
By measuring the change in heterozygosity: ?H = (1/2N) x H
What is the effect of quick size recovery after habitat loss? Explain.
Maintains low heterozygosity. Heterozygosity is increased by introducing mutations. Mutations take a long time to settle within the population.
What is mutation?
Spontaneous generation of a new variation (allele).
What is the mutation rate of humans?
? = 2.5x10^-8 per nucleotide per generation; U = ? x number of nucleotides (per genome per generation).
How can heterozygosity be calculated using ??
?H = 2?(1-H)
What is mutation-drift balance?
Rate of new mutation = Rate of loss of variation due to fixation/extinction.
How can mutation-drift balance be used to calculate heterozygosity of a population?
?H = 2?(1-H); ?H = (1/2N)H; 2?(1-H)=(1/2N)H => H = 4N?/(1+4N?)
How can amount of variation be estimated using only ? and N?
if 1/?>>N - Little/no variation; If 1/?<
What is the difference in variation between SNPs and Microsatellites?
SNP: ?=2.5x10^8; Microsatellites: ?=0.004. N ~10,000; SNPs have little variation. Microsatellites show lots of variation.
What is neutral variation?
Variation in mutation-drift balance. No effect on phenotype - not affected by selection. Often in introns or synonymous mutation.
When can presence of selection be confirmed?
When allele frequencies (variation) departs from H-W and M-D.
What is selection?
Change in allele frequencies in populations associated with changes in relative fitness of the allele phenotypes.
What are the 3 qualitative types of selection?
Artificial, Natural, Sexual.
Describe artificial selection.
Human domestication of animals which are selectively interbred to show the desired phenotype in offspring.
Describe natural selection.
Variation in fitness provided by different alleles allows the most adaptive variants to survive. Main driving force of evolution.
Describe sexual selection.
Driven by preference of opposite sex. Explains sexually appealing traits and their continuous existence (Peacock's tail). Appleal usually reflects health/fitness of the individual. Natural selection with a twist.
What are the 3 quantitative types of selection?
Purifying, Positive, Balancing.
Describe purifying selection.
Rejection of injurious variations - C.Darwin. Removal of deleterious mutations.
What are the effects of purifying selection?
Reduces diversity created by mutations. Maintains conserved DNA sequences.
Give an example of a DNA sequence conserved by purifying selection.
21/30 amino acids of Cytochrome C conserved between animals and plants.
Some deleterious mutations are harder to eradicate than others. What are they?
Non-lethal mutations. Late-onset mutations (Huntington's).
What causes Tay-Sach's Disease?
Mutation of HEXA gene - involved in proper CNS function.
Why is the mutation causing TS, not a dominant mutation?
Completely lethal by reproductive age therefore no chance of inheritance - No fixation.
Give a H-W model for relative fitness of the three genotypes of HEXA.
p^2 = 1; 2pq = 1; q^2 = (1-s)q^2.
What is 's' used for in H-W models?
Selection coefficient. Shows the relative impact of selection on fitness of the genotype.
Describe positive selection.
Alleles that are advantageous to the individual in their environment, are selected for.
What are the effects of positive selection?
Reduction in diversity. Increase in homozygosity until fixation.
Give an example of purifying selection. Explain.
Insecticide resistance in mosquitoes. Even though heterozygotes are resistant, their frequency decreases because of extinction of susceptible individuals.
When may insecticide resistance become deleterious?
Insecticide no longer used. Unnecessary fitness expended on resistance.
Describe balancing selection.
Selection for the heterozygous phenotype. Having both alleles is advantageous (Overdominance) or disadvantageous (Underdominance).
What is the effect of balancing selection?
Increase in variation.
Give an example of Overdominance.
Sickle cell anaemia. Cells not sickle enough to cause problems. Too sickle for plasmodia to reproduce. Geographical distribution of Haemoglobin S allele closely follows distribution of malaria.
Give an example of Underdominance.
How can the significance of selection on a population be determined?
Using the chi squared test on genotype frequencies and seeing whether the departure from H-W is significant or not.
How is relative fitness assigned?
Relative to most fit homozygote (that will have fitness of 1).
With respect to H-W, what is 'h' and how is it calculated?
h is the heterozygote effect. Calculated by using the formula "Relative fitness = 1-hs".
What can be deduced from h values?
If 0 - Allele is recessive; If 1 - allele is dominant; 1>h>0 - Incomplete dominance; h1 - Underdominance.
Why is selection analysis using H-W not always accurate?
Departure will occur without selection if one of the assumptions is broken (false positive). Only tests departure from H-W. Only detects significant departure. Selection may act on a population without H-W departure.
How else can selection be tested for? Describe possible outcomes.
Mutation-Drift balance: H = 4Nu/(1+4Nu). H > Expected - Balancing selection; H < Expected - Positive or Purifying selection.
What are the limitations of using M-D to test for selection?
N is unknown for many species. U is difficult to measure.
What genetic technique can be used to test for selection?
Measuring heterozgosity of multiple SNPs. Polymorphisms with heterozygosity significantly lower than that of others show positive or purifying selection.
What are the assumptions made by using SNP polymorphism?
N will be the same for all SNPs (accurate). U will be the same for all SNPs - not always accurate.
Give an example of reduction of Heterozygosity of a gene because of selection.
IGF1 gene - Insulin-like Growth Factor Gene 1. Determines skeleton size in dogs. Lots of variation in large dogs; Reduced H in small dogs (+ve/purifying selection).
In summary, what are the 3 main selection tests used?
Test for H-W equilibrium. Using heterozygosity values of SNPs. Using a multispecies approach.
What are quantitative traits?
Continuous polymorphic traits. Described by frequency distribution curves.
How can the number of phenotypes of a quantitative gene be derived from number of alleles?
Phenotypes = genes responsible x alleles per gene + 1
What is phenotypic variance? How is it denoted?
Variance due to genes + Variance due to environment. s^2(P) or V(P).
What is broad-sense heritability?
Measure of the degree to which phenotypic variance is due to genes.
What is the formula or broad-sense heritability?
H^2 = s^2g/s^2p = s^2g/(s^2g+s^2e).
What does a H^2 value of 1 represent?
All variation being genetic.
What does a H^2 value of 0 represent?
All variation being environmental.
What is a common misconception regarding H^2?
H^2 describes how much of the trait is genetic. It doesn't, it describes how much of the varitio is genetic.
What is narrow-sense heritability?
Measure of the degree to which s^2p os due to additive genetic factors.
Give an example of a quantitative trait.
Skeleton size in dogs.
How are the genes responsible for skeleton size in dogs found?
Highly variable genetic markers used. Markers which show linkage (co-inherit) with the trait are likely incorporated in the gene sequence of the responsible gene.
What are QTLs?
Variable markers associated with gene responsible for quantitative trait.
What were the findings in dogs regarding skeleton size QTLs?
44QTLs on 22 chromosomes.
What are the requirements for QTL mapping by linkage?
Homozygous strains and crosses. Model organisms. Large pedigree. In humans only useful with traits that have a major genetic component.