Wageningen University & Research, Animal Breeding and Genomics, P.O. Box 338, Wageningen, AH, 6700, the Netherlands.
CRV, Arnhem, the Netherlands.
BMC Genomics. 2020 Jan 28;21(1):89. doi: 10.1186/s12864-020-6496-1.
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.
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 = ~ 0.1 at 10 kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD (r = ~ 0.5 at 10 kb distance).
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.
拷贝数变异（CNVs）是 DNA 片段的增益或缺失，已知它们在塑造广泛的表型方面发挥作用。在这项研究中，我们使用了荷斯坦-弗里森和泽西两个奶牛群体，使用 Illumina BovineHD Genotyping BeadChip 对 ARS-UCD1.2 组装进行了对齐，发现了 CNVs。对发现的 CNVs 进行了功能影响和群体遗传特征的研究。
我们发现了 14272 个常染色体 CNVs，这些 CNVs 聚集在 451 个动物中的 1755 个 CNV 区域（CNVR）中。这些 CNVR 总共覆盖了牛常染色体的 2.8%。对 CNVR 功能影响的评估表明，罕见的 CNVR（MAF<0.01）比常见的 CNVR（MAF≥0.05）更有可能与基因重叠。基于 CNVR 的群体分化指数（Fst）显示，两个品种之间有多个高度分化的 CNVR。其中一些 CNVR 与候选基因重叠，如 MGAM 和 ADAMTS17 基因，分别与淀粉消化和体型有关。最后，CNVR 与 BovineHD BeadChip SNPs 之间的连锁不平衡（LD）通常很低，接近于 0，尽管常见的缺失（MAF≥0.05）在 10kb 距离处的 LD 略高（r≈0.1），但仍低于 SNP-SNP LD（r≈0.5在 10kb 距离处）。
我们的分析表明，使用 BovineHD BeadChip 阵列检测到的 CNVR 很可能是有功能的。这一发现表明，CNVs 可能会破坏基因的功能，从而改变表型。此外，群体分化指数揭示了两个候选基因 MGAM 和 ADAMTS17，它们暗示了两个群体之间的适应性进化。最后，低的 CNVR-SNP LD 意味着，仅依赖 SNP 标记的常规动物遗传评估可能无法完全捕捉到 CNV 带来的遗传变异。
