Transcript Quantitative Genetics of Natural Variation: some questions

Genetic Drift, followed by selection
can cause linkage disequilibrium
Combination of Two Different Gene Pools
Admixture
Recombination Breaks Down Linkage Disequilibria
The rate of decline in LD increases with r
LD declines over time
(rate depending on r)
r=
D
sqrt(pqst)
Concept of Linkage
Law of Independent Assortment
= 0.25
A
Meiosis
a
B
b
= 0.25 All allele combinations
in gametes
equally probable
= 0.25
= 0.25
Probability of recombination = 0.5
A
B
a
b
= 0.25
Meiosis
= 0.25
= 0.25
= 0.25
All allele combinations
in gametes
equally probable
Linked Loci
Probability of recombination = 0.3
A
a
B
b
= 0.35
Meiosis
= 0.15
= 0.15
All allele combinations
in gametes NOT
equally probable
= 0.35
Probability of recombination = 0.1
A
B
a
b
= 0.45
Meiosis
= 0.05
= 0.05
= 0.45
All allele combinations
in gametes NOT
equally probable
Concept: The closer two loci are on a chromosome,
the lower the probability of recombination.
Why important?
(1) Affects rate that LD is broken down.
(2) Allows one to determine the linear order of genes
on a chromosome (make a genome map).
(3) Maps allow for the localization of genes, mutant
phenotypes, and QTL in the genome.
Selection at a single locus affects other loci under LD
Selection has
an effect on
frequency of B
alleles
LD may retard rate of
evolution
If:
new mutations are linked
to deleterious sites or arise
in the ‘wrong’ chromosomal
backgrounds
(255 genes examined)
A comparison of substitution
rates between D. simulans
and D. melanogaster for
synonomous and
non-synonomous sites
LD among 1504 marker
Loci on Human
Chromosome 22.
(Dawson et al. 2002)
Where did CCR5 D32 come from?
There is strong linkage
disequilibrium between
CCR5 and two neutral
marker loci.
Probability that D32-197-215 has remained unchanged across generations:
Pg = (1 - c - m)g
Prob recombination
Prob mutation
Estimated p = 0.848, m = 0.001, c = 0.005
g = 27.5
~ 27.5 x 25 = 688 yrs
How does LD help identify genes that may be under
positive natural selection?
For neutral alleles: Genetic drift is the primary evolutionary
mechanism. So:
If LD is detectable, indicates that an allele is young.
Expect magnitude of LD is proportional to the age of an allele.
If LD is not detectable, indicates that an allele is old.
Expect old and frequent alleles, or old and rare alleles,
But do not expect young, high frequency alleles.
Indicates alleles at the locus may be under selection.
G6PD polymorphism
and deficiency
Countries with malaria
have highest frequency
of a reduced-activity
allele.
LD is higher for the G6PD-202A allele;
suggests positive selection
Probability
that 2 randomly
chosen “a” chromosomes
have the same snps
across a physical
distance