Animal Science Department, School of Agricultural and Veterinary Sciences, São Paulo State University (Unesp), Via de Acesso Paulo Donato Castellane S/N, Departamento de Zootecnia, Jaboticabal, SP, 14884-900, Brazil.
Henry A. Wallace Beltsville Agricultural Research Center, Animal Genomics and Improvement Laboratory, Agricultural Research Service, USDA, Beltsville, MD, 20705-2350, USA.
Sci Rep. 2023 Jun 27;13(1):10399. doi: 10.1038/s41598-023-37586-z.
The wide use of genomic information has enabled the identification of lethal recessive alleles that are the major genetic causes of reduced conception rates, longer calving intervals, or lower survival for live-born animals. This study was carried out to screen the Nellore cattle genome for lethal recessive haplotypes based on deviation from the expected population homozygosity, and to test SNP markers surrounding the lethal haplotypes region for association with heifer rebreeding (HR), post-natal mortality (PNM) and stayability (STAY). This approach requires genotypes only from apparently normal individuals and not from affected embryos. A total of 62,022 animals were genotyped and imputed to a high-density panel (777,962 SNP markers). Expected numbers of homozygous individuals were calculated, and the probabilities of observing 0 homozygotes was obtained. Deregressed genomic breeding values [(G)EBVs] were used in a GWAS to identify candidate genes and biological mechanisms affecting HR, STAY and PNM. In the functional analyses, genes within 100 kb down and upstream of each significant SNP marker, were researched. Thirty haplotypes had high expected frequency, while no homozygotes were observed. Most of the alleles present in these haplotypes had a negative mean effect for PNM, HR and STAY. The GWAS revealed significant SNP markers involved in different physiological mechanisms, leading to harmful effect on the three traits. The functional analysis revealed 26 genes enriched for 19 GO terms. Most of the GO terms found for biological processes, molecular functions and pathways were related to tissue development and the immune system. More phenotypes underlying these putative regions in this population could be the subject of future investigation. Tests to find putative lethal haplotype carriers could help breeders to eliminate them from the population or manage matings in order to avoid homozygous.
基因组信息的广泛应用使人们能够识别出隐性致死等位基因，这些等位基因是导致受孕率降低、产犊间隔延长或活产动物存活率降低的主要遗传原因。本研究旨在根据预期群体纯合度的偏差，对Nellore 牛基因组进行隐性致死单倍型筛选，并对围绕致死单倍型区域的 SNP 标记进行与小母牛再配种（HR）、产后死亡（PNM）和持久力（STAY）的关联测试。这种方法只需要来自外观正常个体的基因型，而不需要来自受影响的胚胎的基因型。共对 62022 头动物进行了基因型检测，并将其遗传到高密度面板（777962 个 SNP 标记）中。计算了预期的纯合个体数量，并获得了观察到 0 个纯合子的概率。去回归基因组育种值[(G)EBV]用于 GWAS，以鉴定影响 HR、STAY 和 PNM 的候选基因和生物学机制。在功能分析中，研究了每个显著 SNP 标记上下游 100kb 范围内的基因。30 个单倍型具有较高的预期频率，但未观察到纯合子。这些单倍型中存在的大多数等位基因对 PNM、HR 和 STAY 都有负面影响。GWAS 揭示了与不同生理机制相关的显著 SNP 标记，这些标记对三个性状都有有害影响。功能分析揭示了 26 个基因富集了 19 个 GO 术语。发现的大多数与生物学过程、分子功能和途径相关的 GO 术语与组织发育和免疫系统有关。这些假定区域在该群体中的更多表型可能是未来研究的主题。寻找潜在致死单倍型携带者的测试可以帮助饲养者从种群中淘汰它们，或者管理交配以避免纯合。
