1. Patterns of Linkage Disequilibrium in the Human Genome
Chris Levasseur
BI 820
March 30, 2003

2. Linkage Disequilibrium (LD)
Particular alleles at neighboring loci tend to be co-inherited. For tightly linked loci this can lead to associations between alleles in the population - LD
Might facilitate mapping of complex disease loci through whole-genome association studies

3. LD Around an Ancestral Mutation

4. Quantifying Linkage Disequilibrium (D)
D = PAB - (PA X PB)
A,a and A,b: two alleles at two adjacent loci (A and B)
PAB: frequency of the haplotype of alleles A and B
PA: frequency of A at the first locus
PB: frequency of B at the second locus
0 < D < PAB Raw measurement of Disequilibrium

5. Absolute Value of Disequilibrium (D’)
D depends on allele frequencies
D’ = (PAB - PA X PB) / (PA X PB)
D’ = 1 if, and only if 2 SNPs have not been separated by recombination during history of the sample (complete LD)
If D’ < 1 then the complete ancestral LD has been disrupted
If D’ = 0 then there is complete linkage equilibrium
* D’ normalizes LD to be between 0 and 1

6. LD Decays Over Time Due to Recombination

7. Quantifying LD Decay Dt = (1 - r)tD0 t = time
r = recombination fraction between markers
D0 = extent of starting point
Dt = extent of disequilibrium t generations later

8. Factors That Influence LD
Collapse
Bottleneck
Diversity LD

9. Factors That Influence LD
Expansion
Diversity LD

10. Factors That Influence LD
Natural selection
Positive selection = LD

11. Conclusions
Lots of variability in the extent of LD from one region of genome to another.
Even in a region of high LD, some pairs of loci do not show useful levels of LD due to gene conversions, allele frequency, etc.
Do not know if patterns of LD in one pop. will be replicated in other pops. w/ differing histories
Many forces shape the patterns of LD in humans (both molecular and demographic forces).