Functional and population genetic features of copy number variations in two dairy cattle populations

Abstract

Background: Copy Number Variations (CNVs) are gain or loss of DNA segments that are known to play a role in shaping a wide range of phenotypes. In this study, we used two dairy cattle populations, Holstein Friesian and Jersey, to discover CNVs using the Illumina BovineHD Genotyping BeadChip aligned to the ARS-UCD1.2 assembly. The discovered CNVs were investigated for their functional impact and their population genetics features.Results: We discovered 14,272 autosomal CNVs, which were aggregated into 1755 CNV regions (CNVR) from 451 animals. These CNVRs together cover 2.8% of the bovine autosomes. The assessment of the functional impact of CNVRs showed that rare CNVRs (MAF < 0.01) are more likely to overlap with genes, than common CNVRs (MAF ≥ 0.05). The Population differentiation index (Fst) based on CNVRs revealed multiple highly diverged CNVRs between the two breeds. Some of these CNVRs overlapped with candidate genes such as MGAM and ADAMTS17 genes, which are related to starch digestion and body size, respectively. Lastly, linkage disequilibrium (LD) between CNVRs and BovineHD BeadChip SNPs was generally low, close to 0, although common deletions (MAF ≥ 0.05) showed slightly higher LD (r 2 =~0.1 at 10 kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD (r 2 =~0.5 at 10 kb distance). Conclusions:Our analyses showed that CNVRs detected using BovineHD BeadChip arrays are likely to be functional. This finding indicates that CNVs can potentially disrupt the function of genes and thus might alter phenotypes. Also, the population differentiation index revealed two candidate genes, MGAM and ADAMTS17, which hint at adaptive evolution between the two populations. Lastly, low CNVR-SNP LD implies that genetic variation from CNVs might not be fully captured in routine animal genetic evaluation, which relies solely on SNP markers.

Assessment of linkage disequilibrium patterns between structural variants and single nucleotide polymorphisms in three commercial chicken populations

“…However, levels of ~40 % of the SNP -SNP LD (Table 1) were higher than what was found e.g. by Lee et al [32], who found DUP -SNP LD to be ~20 % of SNP -SNP LD in two dairy cattle populations. A main factor of DUP -SNP LD being reduced compared to SNP -SNP LD may be due to the lower allele frequencies of DUP in our callset (Figure 2)…”

“…Studies that found DEL -SNP LD to be on a reduced level compared to SNP -SNP LD mostly performed the DEL calling from SNP arrays, which implies low breakpoint resolution [32]. It is also common to merge CNV to copy number variable regions (CNVR) in SNP array or read-depth-based studies [32].…”

Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs

“…To provide the required input for GWAS, specific genotyping for CNVR was necessary. We used in-house script to genotype CNVRs in U.S. and Canadian Duroc pigs into “+/+”, “+/−”, “−/−”, following previous studies [ 74 , 75 ].…”

Copy Number Variants in Four Italian Turkey Breeds

“…CNVs are DNA segments longer more than 50 bp (deleted or duplicated) present at a variable copy number in comparison with a reference genome and affecting gene expression [ 20 ]. As shown in recent literature, CNVs can contribute to understanding the differences both at individual and populations level, in disease susceptibility [ 21 , 22 ], phenotypic, and genome variability also as a response to selection pressure [ 23 , 24 , 25 , 26 ].…”