Copy number variation (CNV) has been recently identified in human and other mammalian genomes and increasing awareness that CNV might be a major source for heritable variation in complex traits has emerged. Despite this, little has been published on CNVs in Holsteins. In order to fill this knowledge-gap, we proposed a genome-wide association study between quantitative trait loci (QTL) for economic traits and CNV in the Holstein cattle. The approved feasibility study was aimed at the genome-wide characterization of CNVs in Holstein cattle and at the demonstrating of their possible association with economic traits by performing the activities of preparation of DNA samples, Comparative Genomic Hybridization (CGH), initial association study between CNVs and production traits and characterization of CNVSNP associations. For both countries, 40 genomic DNA samples of bulls representing the extreme sub-populations for economically important traits were CGH analyzed using the same reference genome on a NimbleGen tiling array. We designed this array based on the latest build of the bovine genome (UMD3) with average probe spacing of 1150 bases (total number of probes was 2,166,672). Two CNV gene clusters, PLA2G2D on BTA2 and KIAA1683 on BTA7 revealed significant association with milk percentage and cow fertility, respectively, and were chosen for further characterization and verification in a larger sample using other methodologies including sequencing, tag SNPs and real time PCR (qPCR). Comparison between these four methods indicated that there is under estimation of the number of CNV loci in Holstein cattle and their complexity. The variation in sequence between different copies seemed to affect their functionality and thus the hybridization based methods were less informative than the methods that are based on sequencing. We thus conclude that large scale sequencing effort complemented by array CGH should be considered to better detect and characterize CNVs in order to effectively employ them in marker-assisted selection.
A genome-wide association study of copy-number variation identifies putative loci associated with osteoarthritis in Koreans
