POPULATION GENETICS

review: markers and haplotypes Mixing of gene pool.

Compare [private] allele frequencies in microsatellites from
markers different sites if similar, gene flow occurred
the usual markers are hard to score for large compare frequencies of allele sizes at different loci
samples similar frequencies of similar sizes indicate gene
flow between sites.
SNP's
RFLP's Applications
Microsatellites 25% of population in Mongolia are descended from
o size variants - can cause diseases Genghis Khan. (Y-chromosome haplotype)
o in pop genetics, we are interested in those - spreads east- and westward (matches Genghis
not inside gene regions Khans movement)
o microsatellites can be used in criminal - proportion of that haplotype appears to
cases - identification of people - if v high decrease as it moves away from Mongolia
variations [?] o diluted as you move away
haplotypes o can estimate when haplotype emerged
(molecular clock) we know that it
emerged recently
selection for haplotype can cause
sudden rise if haplotype is associated
with something that gives great
reproductive advantage, e.g. being
royalty

Human origins Africa

Hardy-Weinberg Equilibrium
in the absence of violations, genetic variations are
not created/destroyed from generation to
generation, i.e., proportion of homozygotes,
heterozygotes, stays the same
1= p2 + 2pq + q2
o allele2 for homozygotes, 2(allele1)(allele2)
for heterozygotes
o sum of genotype frequencies is 1
p+q=1
o sum of allele frequencies is 1
assumptions
o aa
it is the phenomena that lead to changes in allele and
genotype frequencies that make population genetics
interesting. any variations will have interesting causes
Automated genotyping.
(Mitochondrial haplotypes)
- infer pattern of human migration via molecular
clocks, relation to other haplotypes
o Northern wave of migration ice receding
o Lots of haplotypes stayed in Europe
o some crossed the Bering strait, etc
changing haplotype frequency is described as a gradient.
i.e., allele frequencies may vary along a gradient.
spread of CCR532.
- CCR5 codes for CD195, a surface protein on T
cells that allows them to recognize other
members of the _ system.
- CD195 is one of the proteins that HIV uses to
enter
o 32 deletion truncates CD195 makes it
more resistant to HIV
- centered in Scandinavia how did this mutation
spread? (mutation has phenotypic effect)
o hypotheses include cold temperature,
maybe linked to a gene involving vitamin D;
Scandinavian migration outwards due to
Bubonic Plague

- lets say this haplotype was rare but is now

very common.
o migrate with higher chance of survival bc
they have resistance;
o bottleneck effect subpopulation that
became survivors, so next generations had
the gene;
o founder effect small grp fr this area goes
to a place with no people, starts a
haplotype there

Identify the heterozygotes.

Hardy-Weinberg Equilibrium

Mating systems
- HW assumptions: random mating,
- negative (avoid) and positive (preferred) selection

Population size
- assumption: infinite smaller populations will violate
HW more

Mutation
- mutations change frequencies of alleles - this is usu
what starts an allele in the first place

Migration
- assumption: no migration else, this will dilute

Drift
- result of selection selective advantage spreads

Selection
- genocide, etc

Mating systems: non-random mating.

assortive mating
- positive assortive
- negative assertive
isolation by distance
- isolation w/o physical barriers include: racism
(s. africa, w/in china based on langg, etc),
indias caste system
inbreeding, inbreeding depression, and inbreeding
coefficient
- inbreeding increases number of recessibe
changes allele freq very quickly
- e.g. royal families marry first cousins, Amish cult
in PH, illegal up to 4 degrees of consanguinity
(path going to common ancestor)

CASE: The Basque, who live in the Pyrenees between

Spain and France, have one of the highest frequencies of
the d allele in the Rh system so far reported. In one study of
400 Basques, 230 were found to be Rh+ (DD or Dd) and
170 Rh- (dd). Estimate the frequency of the D and d alleles,
the genotype frequencies, and the proportion of Rh+
individuals who are actually heterozygotes Dd. What is the
standard error of the estimate?

Standard error = SQRT(Variance)

Variance = (1-R)/4N, where R is the frequency of
homozygote recessives and N is sample size.
CASE: In a sample of 1,617 Basques, the numbers of A, B,
O, and AB blood types observed were 724, 110, 763, and
20, respectively. Best estimates of allele frequency are p1
(IA) = 0.2661, p2 (IB) = 0.0411, and p3 (IO) = 0.6928.
Calculate the expected numbers of the 4 phenotypes and
carry out a X2 test for goodness of fit to the Hardy Weinberg
expectations.
(need to know geography. Basques: NE, physical barrier
bec mountainous region, small population, hates all the
other Spaniards :^) lots of reason to violate HW)
Case Prob 4: forensics.
At a criminal trial, the prosecutor presents genotypes for 3
microsatellite loci from the FBI CODIS set. He reports that a
DNA sample from the crime scene and one from the
suspect both have the genotype FGA1/FGA4,
TPOX1/TPOX3, VWA2/VWA7 at these three microsatellites.
He also presents the allelic frequencies for the general
population to which the suspect belongs (table).
a. What is the probability that the genotype of the
DNA evidence would match that of the suspect
given that the person who left his DNA sample at
the crime scene and the suspect are different
individuals?
b. Other evidence (e.g., witnesses) suggest that the
suspect has a 60% chance of being the one who
left the material at the crime scene. Given a match,
what is the chance now? A test of this kind gives
false negatives of about 0.001.
 (#14 solution)
Some applications of population genetics.
- to predict forward, and to diagnose situations that
happened in the past.
- how to model effect of selection on hardy weinberg
equation?

1 = po2 + 2poqo + qo2

(standard hardy-weinberg equation)
subscript o represent alleles in the
first/parental generation

= po2wAA + 2poqowAa + qo2waa

1 ***
-
represents average fitness. there is a
fitness value w that changes/affects
your current allele frequencies (po, qo,
etc). ie, new allele freqs will be
adjusted by .
- note: values for w are not v far from 1. if
w = 1, no selection/fitness, then we get
1 = p2 + 2pq + q2

multiplying proportions by actual number of individuals N,

= N (po2wAA + 2poqowAa + qo2waa)
N
= Npo2wAA + N2poqowAa + Nqo2waa
N

To get the allele freq q after a number of generations t:

Consider: which terms from the parental generation

contribute q alleles?
- homo*2 (q2, contributes two q alleles)
and het (2pq, contributes one q
allele).

homo: (Nqo2waa) * 2
het: N2poqowAa

divide these terms by the total number of alleles number

of individuals (adjusted by average fitness
) multiplied by Note: mawawala si q sa population bc its being selected
two, since each individual has two alleles against (0.7 fitness < 1)

2 2 + 2 (previous case was diploid)

= slight difference: diploid vs haploid
2
Case: selection in a bacterium.
In a bacterium (haploid), the change in the frequency of
simplifying (cancel out 2N), allele p in a given number of generations t is indicated
2 + below. Contrast this with the diploid version.
= Significant resistance to an antibiotic was induced in a

bacterium over 300 generations. An SNP of traC was found
to increase from an initial frequency of 0.85 to 0.99.
expanding average fitness
in the denominator (***),
2 + Calculate the selective coefficient (s) of traC given that
= W A = 1+s and W a = 1.

2 + 2 + 2

given fitness values, what will be the new proportions in the next = for haploid
generation? +
#14.
The relative fitness of three genotypes are wAA = 1, wAa =
1.0, and waa = 0.7.
a. If the population starts at the allele frequency p = / + /
0.5, what is the value of p in the next generation? = for diploid
b. What is the predicted equilibrium allele frequency if
the rate of mutation of A to a is 0.00002?
 Another use of hardy-weinberg.
Given the frequency of heterozygotes of 100 Polynesians,
Ho = 0.8 or 80% heterozygotes @ t=0, what happens to this
frequency after 5 generations (i.e., find Ht at t = 5)?
1
= [1 ] 0
2

so, frequency of heterozygotes: 0.8 (t=0) 0.78 (t=5)

Hets decrease when small population. same situation in
inbreeding! this is why animals become purebred over time
We can actually det the proportion at any time in the future /
(if small populations are bred)
for any number of generations.
on inbreeding & inbreeding coefficients
Given that you have a rare allelewe start with po = 0.05.
Given p=0.5 and q=0.5, what is the expected number of
we bring this to saturation: pt = 0.99. given the selective
homozygous p? homozygous q? N = 1000.
coefficient s = 0.1, we can now calculate for t (how many
generations will it take to get to saturation?)

Note: this applies only to the mutant allele; we hold the other
fitness value w constant (wa=1) as the other varies (wA=?)

There is deviation of actual vs expected (actual # of

heterozygotes is lesssuspicion is inbred!)

Now, we calculate the inbreeding coefficient F:

=

where He is expected, and Ho is the observed,
number of individuals or frequency of individuals.

Note: to compare,
brother x sister = 0.25
self x self = 0.5

so 0.4 is pretty high! this is the kind of F you see in plants.