Tao Lin, Liu Hang, Adeola Adeniyi C, Xie Hai-Bing, Feng Shu-Tang, Zhang Ya-Ping
Key Laboratory of Genetic Evolution & Animal Models and Yunnan Key Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
BMC Genomics. 2025 Jan 6;26(1):6. doi: 10.1186/s12864-024-11189-y.
Since their domestication, recent inbreeding together with intensive artificial selection and population bottlenecks have allowed the prevalence of deleterious mutations and the increase of runs-of-homozygosity (ROH) in domestic pigs. This makes pigs a good model to understand the genetic underpinnings of inbreeding depression.
Here we integrated a comprehensive dataset comprising 7239 domesticated pigs and wild boars genotyped by single nucleotide polymorphism (SNP) chips, along with phenotypic data encompassing growth, reproduction and disease-associated traits. Our study revealed differential ROH landscapes during domestication and artificial selection of Eurasian pigs. We observed associations between ROH burden and phenotypic traits such as body conformation and susceptibility to diseases like scrotal hernia. By examining associations of whole-genome and regional ROH burden with gene expression, we identified specific genes and pathways affected by inbreeding depression. Associations of regional ROH burden with gene expression also enabled the discovery of novel regulatory elements. Lastly, we inferred recessive lethal mutations by examining depletion of ROH in an inbred population with relatively small sample size, following by fine mapping with sequencing data.
These findings suggested that both phenotypic and genetic variations have been reshaped by inbreeding, and provided insights to the genetic mechanisms underlying inbreeding depression.
自驯化以来，近期的近亲繁殖以及强烈的人工选择和种群瓶颈使得有害突变在家猪中普遍存在，纯合子片段（ROH）增加。这使得猪成为了解近亲繁殖衰退遗传基础的良好模型。
在此，我们整合了一个综合数据集，包括7239头通过单核苷酸多态性（SNP）芯片进行基因分型的家猪和野猪，以及涵盖生长、繁殖和疾病相关性状的表型数据。我们的研究揭示了欧亚猪驯化和人工选择过程中不同的ROH图谱。我们观察到ROH负担与体型等表型性状以及阴囊疝等疾病易感性之间的关联。通过检查全基因组和区域ROH负担与基因表达的关联，我们确定了受近亲繁殖衰退影响的特定基因和途径。区域ROH负担与基因表达的关联还促成了新调控元件的发现。最后，我们通过检查样本量相对较小的近交群体中ROH的缺失情况，随后利用测序数据进行精细定位，推断出隐性致死突变。
这些发现表明近亲繁殖重塑了表型和遗传变异，并为近亲繁殖衰退的遗传机制提供了见解。
