Analysis of copy number variations among diverse cattle breeds
Analysis of copy number variations among diverse cattle breeds
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DOI：
10.1101/gr.105403.110
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发表时间：
2010-05-01
期刊：
影响因子：
7
通讯作者：
Keele, John W.
中科院分区：
文献类型：
--
作者：
Liu, George E.;Hou, Yali;Keele, John W.
基因组结构变异是遗传和表型变异的重要来源。在这里，我们描述了第一个系统的和全基因组的分析拷贝数变异（CNVs）在现代驯化牛使用阵列比较基因组杂交（阵列CGH），定量PCR（qPCR），荧光原位杂交（FISH）。阵列CGH面板包括来自11头普通牛、3头印度牛和3个牛肉、乳制品或双重用途的复合品种的90头动物。我们总共鉴定了200多个候选CNV区域（CNVRs），已知染色体中有177个，这些区域包含或邻近获得或丢失。这177个高置信度的CNVRs覆盖了28.1兆碱基或约1.07%的基因组。超过50%的CNVRs（89/177）在多种动物或品种中发现，分析显示了品种特异性频率差异，并反映了这些牛品种的已知祖先。通过使用qPCR和FISH的独立方法进一步验证选择的CNV。约67%的CNVRs（119/177）完全或部分跨越牛基因，61%的CNVRs（108/177）直接与片段重复重叠。CNVRs涵盖了约400个注释的牛基因，这些基因显著富集了特定的生物学功能，如免疫、泌乳、繁殖和反刍。包括ULBP在内的多个基因家族已经经历了反刍动物谱系特异性基因扩增。我们检测并证实了不同品种之间CNV频率的显著差异，表明一些牛CNV可能在品种中独立出现，并导致品种差异。我们的研究结果提供了微卫星和单核苷酸多态性之外的宝贵资源，可为未来的牛基因组研究探索遗传变异的完整维度。
Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or similar to 1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.