Lecture 6

Question 1

Jukes and Cantor

2

Answer 1

• Corrects for multiple hits

- Assumes all nucleotides are equal

Question 2

Fst:

Answer 2

A derivative of the Hardy Weinburg equation

Question 3

Hardy-Weinberg Equilibrium:

3

Answer 3

• Relating gene frequencies to allele frequencies
• AA, Aa and aa, are related p2, 2pq q2
• If the gene frequency (p) of A = 80/100 the expected genotype frequencies are
  (0.8 x 0.8) = 0.64 AA,
  (2 x 0.8 x 0.2) = 0.32 Aa
  and (0.2 x 0.2) = 0.4 aa

Question 4

What is the heterozygosity of trapped mice in the East (aa) West (AA) population with cats patrolling the middle?
(3)

Answer 4

• Assume we catch as many eat mice as west mice..
• Expected heterozygosity (Hexp) = 2pq = 2 x 0.5 x 0.5 = 0.5
• Observed heterozygosity -(Hexp) = 0

Question 5

Wrights fixation Index (F):

5

Answer 5

• F = (Hexp - Hobs)/Hexp
• The deviation between expected and observed normalized by expected
• F = 0, then HWE, no population structure
• F = 1, there are no heterozygotes, population structure
• The closer F is to 1 the more structure there is in the population
• Tells us how much the population is out of HWE

Question 6

A deficit in heterozygotes can arise due to..

Answer 6

A cryptic population structure

Question 7

When chi-squared gives P<0.001

Answer 7

• Far fewer heterozygotes than we would expect
• Deficit of heterozygotes
• Wahlund effect

Question 8

Wahlund effect:

Answer 8

• When a sample from a population shows that there are actually two populations
• A deficit of heterozygotes is shown

Question 9

Linanthus parryae the ‘desert snow’ helps us study..

Answer 9

• The scale of population structure (regional, global), using the F indices

Question 10

HT=

Answer 10

Total heterozygosity

Question 11

HS=

Answer 11

Subpopulation heterozygosity

Question 12

HR=

Answer 12

Regional heterozygosity

Question 13

Using the Wrights Fixation Indices (F) we can answer these questions:

Answer 13

• How much of the deviation from HWE is due to
• Sub-population structure
• Regional population structure
• Population wide deviations
• Fewer heterozygotes at the individual level

Question 14

FSR =

Answer 14

The decrease in He among subpopulations within regions normalised by He in regions

Question 15

FRT =

Answer 15

• The decrease in He among regions within whole populations normalised by He in whole populations
• A measure of differences of heterozygosity between geographical regions

Question 16

FST =

Answer 16

• The decrease in He among subpopulations within whole populations normalised be He in whole populations
• Calculating F stat based on data from sub populations, vs the total population

Question 17

FIT =

Answer 17

The individual vs the total population, the range that these values take is -1 through 1 (because all individuals may be heterozygotes

Question 18

Fst is the most commonly used because

3

Answer 18

• We just need gene frequencies from ‘subpopulations’
• It is the most informative way to relate subpopulation sample to the total population
• The proportion of the total heterozygosity in the population that is due to differences in the allele frequencies among subpopulations

Question 19

Fst = 0 - 0.05

Answer 19

Low genetic differentiation, very low population structure

Question 20

Fst = 0.05 - 0.15

Answer 20

Moderate genetic differentiation, moderate population structure

Question 21

Fst = 0.15 - 0.25

Answer 21

Great genetic differentiation, great population structure

Question 22

Fst = 0.25 - 1

Answer 22

Very great genetic differentiation, very great population structure, lots of gene flow between them

Question 23

Hapmap project in humans

Answer 23

• Sample from four human populations Central European Populations, Yoruba (Nigerian tribe), Chinese and Japanese
• Figure out how much population structure there is between human populations

Question 24

The hapmap project found:

Answer 24

• Fst of over 2.8 millian SNOS is 0.11 (moderate structure), some sites have structure, others don’t
• Of the total genetic variation observed between these four ethnic groups, only around 11% is due to genetic differences among groups
• ie: about 89% of the variation is common
• We observed the same variants in all populations.

Question 25

Why would Fst differ across the genome?

Answer 25

- In neutral sequences Fst is determined by drift and demography (spread and bottle necks) and chance - Local positive selection increase Fst - Balancing and negative selection decreases Fst

Question 26

Which variants showed us the most variation across human genomes?

Answer 26

- The lactase gene (Lct) - For many people the ability to digest lactase disappears in childhood (ages 3 - 4) - Lactase persistence is in high frequencies among populations with histories of cattle/dairy farming - This is due to natural selection favouring the lactase persistance allele