Characteristics of linkage disequilibrium in North American Holsteins

Background: Effectiveness of genomic selection and fine mapping is determined by the level of linkage disequilibrium (LD) across the genome. Knowledge of the range of genome-wide LD, defined as a non-random association of alleles at different loci, can provide an insight into the optimal density and location of single-nucleotide polymorphisms (SNPs) for genome-wide association studies and can be a keystone for interpretation of results from QTL mapping. Results: Linkage disequilibrium was measured by vertical bar D'vertical bar and r(2) between 38,590 SNPs (spaced across 29 bovine autosomes and the X chromosome) using genotypes of 887 Holstein bulls. The average level of vertical bar D'vertical bar and r2 for markers 40-60 kb apart was 0.72 and 0.20, respectively in Holstein cattle. However, a high degree of heterogeneity of LD was observed across the genome. The sample size and minor allele frequency had an effect on vertical bar D'vertical bar estimates, however, r(2) was not noticeably affected by these two factors. Syntenic LD was shown to be useful for verifying the physical location of SNPs. No differences in the extent of LD and decline of LD with distance were found between the intragenic and intergenic regions. Conclusions: A minimal sample size of 444 and 55 animals is required for an accurate estimation of LD by vertical bar D'vertical bar and r(2), respectively. The use of only maternally inherited haplotypes is recommended for analyses of LD in populations consisting of large paternal half-sib families. Large heterogeneity in the pattern and the extent of LD in Holstein cattle was observed on both autosomes and the X chromosome. The extent of LD was higher on the X chromosome compared to the autosomes.