Sun Lixia, Yuan Chao, Guo Tingting, Bai Yaqin, Lu Zengkui, Liu Jianbin
Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
BMC Genomics. 2025 Jan 22;26(1):60. doi: 10.1186/s12864-025-11207-7.
Prolonged natural selection and artificial breeding have contributed to increased uniformity within the Tibetan sheep population, resulting in a reduction in genetic diversity and the establishment of selective signatures in the genome. This process has led to a loss of heterozygosity in specific genomic regions and the formation of Runs of Homozygosity (ROH). Current research on ROH predominantly focuses on inbreeding and the signals of selection; however, there is a paucity of investigation into the genetic load and selective pressures associated with ROH, both within these regions and beyond. On one hand, genes located situated ROH hotspot regions exhibit a degree of conservation in their genomic segments; on the other hand, these regions may also serve as critical loci for identifying signals of selection.
High-throughput re-sequencing technology was utilized to investigate the ROH hotspot regions across 11 Tibetan sheep populations, resulting in the identification of ten conserved genes (ARHGEF16, Tom1l2, PRDM16, PEMT, SREBF1, Rasd1, Nt5m, MED9, FLCN, RAI1) that are associated with lipid metabolism, lactation, and development. These genes exhibited highly conserved within the ROH hotspot regions across all Tibetan sheep populations. Employing the integrated haplotype score (iHS) method, we screened for selective sites within frequently observed ROH hotspot regions to elucidate genomic differences among Tibetan sheep populations. A comprehensive analysis was conducted, involving Rnhom, dN/dS ratios, missense/synonymous ratios, and loss-of-function (LOF)/synonymous ratios, to investigate the accumulation of deleterious genes and the associated genetic load both within and outside ROH hotspot regions. The results revealed a higher accumulation of deleterious genes and a reduced genetic load within the ROH regions.
This study provides a comprehensive and precise genomic analysis and interpretation of Tibetan sheep, offering theoretical basis for genetic breeding and evolution in Tibetan sheep.
长期的自然选择和人工选育使得藏绵羊群体内的一致性增加，导致遗传多样性降低，并在基因组中形成了选择印记。这一过程导致特定基因组区域杂合性的丧失以及纯合子连续片段（ROH）的形成。目前关于ROH的研究主要集中在近亲繁殖和选择信号方面；然而，对于这些区域内外与ROH相关的遗传负荷和选择压力的研究却很少。一方面，位于ROH热点区域的基因在其基因组片段中表现出一定程度的保守性；另一方面，这些区域也可能是识别选择信号的关键位点。
利用高通量重测序技术对11个藏绵羊群体的ROH热点区域进行了研究，鉴定出10个与脂质代谢、泌乳和发育相关的保守基因（ARHGEF16、Tom1l2、PRDM16、PEMT、SREBF1、Rasd1、Nt5m、MED9、FLCN、RAI1）。这些基因在所有藏绵羊群体的ROH热点区域内高度保守。采用综合单倍型评分（iHS）方法，在频繁观察到的ROH热点区域内筛选选择位点，以阐明藏绵羊群体之间的基因组差异。进行了全面分析，包括Rnhom、dN/dS比值、错义/同义比值和功能丧失（LOF）/同义比值，以研究ROH热点区域内外有害基因的积累及其相关的遗传负荷。结果显示，ROH区域内有害基因的积累更高，遗传负荷更低。
本研究为藏绵羊提供了全面而精确的基因组分析和解读，为藏绵羊的遗传育种和进化提供了理论依据。
