Ladeira Giovanni C, Pinedo Pablo J, Santos José E P, Thatcher William W, Rezende Fernanda M
Department of Animal Sciences, University of Florida, 2250 Shealy Drive, PO Box 110910, Gainesville, FL, 32611, USA.
Department of Animal Sciences, Colorado State University, Fort Collins, CO, USA.
BMC Genomics. 2025 Apr 16;26(1):381. doi: 10.1186/s12864-025-11536-7.
Copy number variations (CNVs) are an important source of genomic variation that play an active role in modulating biological processes by altering gene expression and dosage. These structural variants involve duplications and deletions of segments usually exceeding 1 kilobase in size, dispersed throughout the genome of humans and livestock individuals. We mapped CNVs from high-density single-nucleotide polymorphism (SNP) genotyping array data on 3,601 Holsteins. Following, we explored their association with reported quantitative trait loci (QTLs), genes, and biological pathways, unveiling the potential biological contributions of CNVs to economically important traits in the dairy industry and breeding programs.
We identified 4,113 non-redundant high-confidence CNVs, of which 78% were deletions and 22% duplications, distributed across all bovine autosomal chromosomes (BTA). Out of the 1,184 compiled CNV regions (CNVRs) covering 3.02% of the autosomal genome, 199 novel CNVRs were mapped. QTLs overlapping with CNVRs detected in this study were enriched for 140 economically important traits, such as milk yield, conception and pregnancy rates, susceptibility to diseases and length of productive life, indicating that CNVs likely underlie productive, reproductive and health performance in Holstein dairy cattle. Moreover, detected CNVRs overlapped with 2,788 annotated genes, including those linked to milk production, fertility, and immune response in cattle, such as DGAT1, AFF1, and ADAMTS13 genes. Furthermore, the gene set analysis revealed GO terms related to metabolic processes, immune system, response to stimulus, and cellular binding activities. Notably, enriched GO terms highlighted relevant genes to cattle health and reproduction overlapping CNVRs, such as DEFB4A, GATA3, GNB1, and PPP1R1B.
We mapped and demonstrated the characteristics of genome-wide distributed CNVs in a large commercial Holstein population genotyped with a high-density SNP array. Collectively, the results emphasize the role of CNVs as a valuable resource of genetic variation and contribute to better understand the genetic architecture of economic complex traits in dairy cattle. Furthermore, these findings may provide opportunities for the development of novel and enhanced genomic selection strategies in Holstein cattle.
拷贝数变异（CNV）是基因组变异的一个重要来源，通过改变基因表达和剂量在调节生物过程中发挥积极作用。这些结构变异涉及通常超过1千碱基大小的片段的重复和缺失，分散在人类和家畜个体的整个基因组中。我们从3601头荷斯坦奶牛的高密度单核苷酸多态性（SNP）基因分型阵列数据中绘制了CNV图谱。随后，我们探索了它们与已报道的数量性状位点（QTL）、基因和生物途径的关联，揭示了CNV对奶牛业经济重要性状和育种计划的潜在生物学贡献。
我们鉴定出4113个非冗余的高可信度CNV，其中78%为缺失，22%为重复，分布在所有牛的常染色体（BTA）上。在1184个编译的CNV区域（CNVR）中，覆盖了常染色体基因组的3.02%，其中199个新的CNVR被绘制出来。本研究中检测到的与CNVR重叠的QTL富集了140个经济重要性状，如产奶量、受孕率和妊娠率、疾病易感性和生产寿命长度，这表明CNV可能是荷斯坦奶牛生产、繁殖和健康性能的基础。此外，检测到的CNVR与2788个注释基因重叠，包括那些与奶牛产奶、繁殖力和免疫反应相关的基因，如DGAT1、AFF1和ADAMTS13基因。此外，基因集分析揭示了与代谢过程、免疫系统、对刺激的反应和细胞结合活动相关的基因本体（GO）术语。值得注意的是，富集的GO术语突出了与牛健康和繁殖相关的重叠CNVR的相关基因，如DEFB4A、GATA3、GNB1和PPP1R1B。
我们绘制并展示了在一个使用高密度SNP阵列进行基因分型的大型商业荷斯坦牛群体中全基因组分布的CNV的特征。总体而言，这些结果强调了CNV作为遗传变异的宝贵资源的作用，并有助于更好地理解奶牛经济复杂性状的遗传结构。此外，这些发现可能为荷斯坦牛新型和改进的基因组选择策略的开发提供机会。
