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通过表观基因组数据对家畜功能变异进行注释和评估。

Annotation and assessment of functional variants in livestock through epigenomic data.

作者信息

Ma Ruixian, Kuang Renzhuo, Zhang Jingcheng, Sun Jiahao, Xu Yueyuan, Zhou Xinbo, Han Zheyu, Hu Mingyang, Wang Daoyuan, Fu Yuhua, Zhang Yong, Li Xinyun, Zhu Mengjin, Zhao Shuhong, Xiang Tao, Shi Mengwei, Zhao Yunxia

机构信息

Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China.

出版信息

J Genet Genomics. 2025 Apr 4. doi: 10.1016/j.jgg.2025.03.013.

Abstract

Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding. However, the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods. In this study, we gather 1030 raw epigenomic datasets from 10 farm animal species and systematically annotate 7 types of key regulatory regions, creating a comprehensive functional annotation map of animal genomic variants. Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits, underscoring the utility of these annotations in functional variant discovery. Using our functional annotations, we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories, with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs. Incorporating these variants into genomic prediction models can improve estimated breeding value (EBV) accuracy, demonstrating their practical utility in breeding programs. To facilitate the use of our results, we develop the Integrated Functional Mutation (IFmut: http://www.ifmutants.com:8212) platform, enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently. Our study provides a robust framework for functional genomic annotations in farm animals, enhancing variant function assessment and breeding precision.

摘要

了解基因变异的功能对于推进动物基因组学和精准育种至关重要。然而,动物中缺乏全面的功能基因组注释限制了大多数变异功能评估方法的有效性。在本研究中,我们收集了来自10种家畜物种的1030个原始表观基因组数据集,并系统地注释了7种关键调控区域,创建了动物基因组变异的综合功能注释图谱。我们的研究结果表明,将变异与调控注释相结合可以识别经济性状背后的组织和细胞类型,突出了这些注释在功能变异发现中的实用性。利用我们的功能注释,我们对基因变异的功能潜力进行排名,并将超过1.27亿个候选变异分为5个功能置信度类别,高置信度变异在eQTL和性状相关SNP中显著富集。将这些变异纳入基因组预测模型可以提高估计育种值(EBV)的准确性,证明了它们在育种计划中的实际应用价值。为了便于使用我们的结果,我们开发了综合功能突变(IFmut:http://www.ifmutants.com:8212)平台,使研究人员能够有效地探索调控注释并评估动物变异的功能潜力。我们的研究为家畜功能基因组注释提供了一个强大的框架,提高了变异功能评估和育种精度。

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