Lecture 3: Linkage Disequilibrium Population Genetics

Linkage Disequilibrium

• nonrandom association of alleles at different loci into gametes

• aka gametic phase disequilibrium or gametic

disequilibrium

• loci may be linked or not

• can arise from intermixture of populations with different gene

frequencies , or from chance in small populations

Linkage Disequilibrium
• biologically, it means that the frequency of the genotype A1B1/A2B2 is
not equal to the frequency of the genotype A1B2/A2B1, even though
each genotype is heterozygous for both loci
• can be expressed by reference to genotypes by comparing the
frequencies of coupling and repulsion double heterozygotes
Genotype Frequency
A1 B1/ A2 B2 coupling heterozygote 2ru
A1 B2/ A2 B1 repulsion heterozygote 2st

Genes A1 A2 B1 B2
Gene frequencies pA qA pB qB
Gametic types A1 B1 A1 B2 A2 B1 A 2 B2
Frequencies, equilibrium pA pB pA qB qA pB qA qB
Frequencies, actual r s t u

Difference from equilibrium +D -D -D +D

Linkage Disequilibrium Linkage Disequilibrium

• a parameter designated D, measures the nonrandom

association, D = ru – st Example: The genes for the human MN and Ss blood groups, are
determined by closely linked genes in chromosome 4. A sample of
• when D = 0, the gametic frequencies equal the products of the 1,000 British people yielded the following numbers of each
relevant allelic frequencies, and the loci are said to be in chromosome type:
linkage equilibrium or LE MS 474 Ms 611 NS 142 Ns 773

Compute the allele frequencies from these data. Compute the

estimated value of D and determine if it is significantly different
from 0.

JP Quilang 1
Lecture 3: Linkage Disequilibrium Population Genetics

• another measure of LD is  D
 Other Measures of Linkage Disequilibrium
p A q A pB qB
 goodness of fit Test • the absolute value of D’

D
Ho: D = 0
D'  if D  0
Ha: D ≠ 0
min  p A qB , q A pB 
   n where n is the number of
D
computed chromosomes in the sample D'  if D  0
min  p A pB , q A qB 
 
tabular
 
df 1,

• r2
 computed
   tabular Reject Ho

Linkage Disequilibrium

• when a population in linkage disequilibrium mates at random,

the amount of disequilibrium is progressively reduced with
each succeeding generation

• After any number of t generations, the disequilibrium is given

by

Dt = Do(1 – c)t where c is the recombination frequency

• LE between genes is eventually attained under random mating

and the assumptions for HWE
Approach to equilibrium under random mating of two loci, considered jointly. The graphs
show the amount of disequilibrium, D, relative to the disequilibrium in generation 0. The
five graphs refer to different degrees of linkage between the two loci, as indicated by the
recombination frequency shown alongside each graph. The graph marked 0.5 refers to
unlinked loci.

Linkage Disequilibrium

• for most pairs of genes in natural populations, D is 0 or close

to 0, unless the genes are very tightly linked (separated by
about less than 100 kb)

• disequilibrium of a disease gene with closely linked marker

can be useful for genetic counseling

• also useful for selection for quantitative characters and in

determining the breeding history of the population

JP Quilang 2