Abstract
BackgroundCopy number variation (CNV) has been recently identified in human and other mammalian genomes, and there is a growing awareness of CNV's potential as a major source for heritable variation in complex traits. Genomic selection is a newly developed tool based on the estimation of breeding values for quantitative traits through the use of genome-wide genotyping of SNPs. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip, which includes 54,001 SNPs (~SNP/50,000 bp), some of which fall within CNV regions.ResultsWe used the BeadChip data obtained for 912 Israeli bulls to investigate the effects of CNV on SNP calls. For each of the SNPs, we estimated the frequencies of occurrence of loss of heterozygosity (LOH) and of gain, based either on deviation from the expected Hardy-Weinberg equilibrium (HWE) or on signal intensity (SI) using the PennCNV "detect" option. Correlations between LOH/CNV frequencies predicted by the two methods were low (up to r = 0.08). Nevertheless, 418 locations displayed significantly high frequencies by both methods. Efficiency of designating large genomic clusters of olfactory receptors as CNVs was 29%. Frequency values for copy loss were distinguishable in non-autosomal regions, indicating misplacement of a region in the current BTA7 map. Analysis of BTA18 placed major quantitative trait loci affecting net merit in the US Holstein population in regions rich in segmental duplications and CNVs. Enrichment of transporters in CNV loci suggested their potential effect on milk-production traits.ConclusionsExpansion of HWE and PennCNV analyses allowed estimating LOH/CNV frequencies, and combining the two methods yielded more sensitive detection of inherited CNVs and better estimation of their possible effects on cattle genetics. Although this approach was more effective than methodologies previously applied in cattle, it has severe limitations. Thus the number of CNVs reported here for the Holstein breed may represent as little as one-tenth of inherited common structural variation.
Highlights
Copy number variation (CNV) has been recently identified in human and other mammalian genomes, and there is a growing awareness of copy number variations (CNVs)’s potential as a major source for heritable variation in complex traits
Hardy-Weinberg equilibrium (HWE)-based detection of CNV We used the data obtained for 912 Holstein bulls to investigate the effects of CNVs on BovineSNP50 BeadChip calls
Expansion of HWE and PennCNV analyses enabled an estimation of loss of heterozygosity (LOH)/CNV frequencies, and combining these methods yielded better detection of inherited CNVs
Summary
Copy number variation (CNV) has been recently identified in human and other mammalian genomes, and there is a growing awareness of CNV’s potential as a major source for heritable variation in complex traits. Genomic selection is a newly developed tool based on the estimation of breeding values for quantitative traits through the use of genome-wide genotyping of SNPs. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip, which includes 54,001 SNPs (~SNP/50,000 bp), some of which fall within CNV regions. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip [1], which includes 54,001 SNPs (~SNP/50,000 bp) This chip may capture any genetic variance that is genetically linked to these markers, as well as copy number variations (CNVs) [2,3]. CNV regions (CNVRs) encompassing adjacent or overlapping losses or gains cover 12% of the human genome This source of variation has more nucleotide content per genome than SNPs [4]. Assuming an average spontaneous CNV mutation rate of 1/10,000 per locus [5], it is expected that a considerable portion of the reported entries arise from de novo CNVs of a sporadic nature
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
