Extent of third-order linkage disequilibrium in a composite line of Iberian pigs

[Background], Previous studies on linkage disequilibrium have investigated second order linkage disequilibrium in animal and plant populations. The objective of this paper was to investigate the genome-wide levels of third order linkage disequilibrium in a composite line founded by admixture of four Iberian pig strains. A model for the generation of third order linkage disequilibrium by population admixture is proposed. A computer Expectation-Maximization algorithm is developed and applied to the estimation of third order linkage disequilibrium at inter- and intra-chromosomal level using 26,347 SNPs typed in 306 sows. The relationship of third order linkage disequilibrium with physical distance was investigated over 35 million triplets in SSC12. Basic and normalized estimates of inter and intra-chromosomal third order linkage disequilibrium are reported. [Results], Genome-wide analyses revealed that third order linkage disequilibrium is rather common among linked loci in this Iberian pig line. It is shown that population admixture of multiple populations may explain the observed levels of third order linkage disequilibrium although it could be generated by genetic drift. Third order linkage disequilibrium decreases rapidly up to 4 Mb and then declines slowly. The short distances between consecutive markers explain the maintenance of the observed third order linkage disequilibria levels when using a model incorporating the break-up of disequilibrium by recombination. Genome-wide testing also revealed that only 3.6% of the normalized estimates were different from 1, − 1, 0, or from a not well-defined situation in which there is only one possible value for the third order linkage disequilibrium parameter, given allele frequencies and pairwise linkage disequilibria parameters. [Conclusions], Third order linkage disequilibrium is common among linked markers in the analyzed pig line and may have been generated by population admixture of multiple populations or by genetic drift. As with second order linkage disequilibrium, the absolute value of the third order linkage disequilibrium decreases with physical distance. Normalization of third order linkage disequilibrium should be avoided for closely linked bi-allelic loci.

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