Characterizing linkage disequilibrium in pig populations

Abstract

Knowledge of the extent and range of linkage disequilibrium (LD), defined as non-random association of alleles at two or more loci, in animal populations is extremely valuable in localizing genes affecting quantitative traits, identifying chromosomal regions under selection, studying population history, and characterizing/managing genetic resources and diversity. Two commonly used LD measures, r(2) and D', and their permutation based adjustments, were evaluated using genotypes of more than 6,000 pigs from six commercial lines (two terminal sire lines and four maternal lines) at ~4,500 autosomal SNPs (single nucleotide polymorphisms). The results indicated that permutation only partially removed the dependency of D' on allele frequency and that r(2) is a considerably more robust LD measure. The maximum r(2) was derived as a function of allele frequency. Using the same genotype dataset, the extent of LD in these pig populations was estimated for all possible syntenic SNP pairs using r(2) and the ratio of r(2) over its theoretical maximum. As expected, the extent of LD highest for SNP pairs was found in tightest linkage and decreased as their map distance increased. The level of LD found in these pig populations appears to be lower than previously implied in several other studies using microsatellite genotype data. For all pairs of SNPs approximately 3 centiMorgan (cM) apart, the average r(2) was equal to 0.1. Based on the average population-wise LD found in these six commercial pig lines, we recommend a spacing of 0.1 to 1 cM for a whole genome association study in pig populations.

Figure 1

Expected r²_max as a function of minor allele frequency (MAF) under the assumption of MAF at two loci are independently and uniformly distributed. Given allele frequencies at two biallelic loci, the global and local r²_max were calculated using Eqs. 5 and 6, respectively.

Figure 2

Average of observed D' as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 3

Average of observed r² as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 4

Average D' under independence (D'_H0) as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 5

Average r² under independence (r²_H0) as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 6

Average D' adjusted by recombination rate and D'_H0 as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 7

Average r² adjusted by recombination rate and r²_H0 as a function of average frequency of the minor alleles at each pair of SNPs in six pig lines. The breed origins of all lines were described in Table 1.

Figure 8

Average of the observed LD measures adjusted by recombination rate as a function of map distance between two SNPs of each pair. A, r²; B, r²/ r²_max as defined in Eq. 5.

Figure 9

Standard deviation of the observed LD measures adjusted by recombination rate as a function of map distance between two SNPs of each pair. A, r²; B, r²/ r²_max as defined in Eq. 5.