Genome-wide analysis identified candidate variants and genes associated with heat stress adaptation in Egyptian sheep breeds

The current study was conducted from 2009 to 2019 in three hot and dry agroecological zones in Egypt: Western Desert coastal zone, New Valley desert oasis, and hot-dry Upper Egypt. Within these zones, three local sheep breeds were studied: Barki (83 ewes), Wahati (55 ewes) and Saidi (68 ewes). During the study period, the animals exercised under natural heat stress (simulating summer grazing on poor pasture). Meteorological and physiological parameters were measured and recorded. The heat tolerance index of the animals was calculated to identify animals with high and low heat tolerance based on the animals' response to the five main physiological parameters (scale from 0 to 5). DNA samples were extracted for genomic analysis. The genetic diversity measurements showed a significant influence of breed and location on the populations. The influence of breed is more significant than that of location. The inbreeding analysis shows that the desert breeds (Wahati and Barki) have lower values than the urban breed (Saidi). The high rate of sub-clustering indicates the process of sub-population through inbreeding pressure. Wahati and Barki are very distinct breeds with strong identification, while Saidi breed has crosses with other breeds. The most significant SNPs associated with heat tolerance were found in MYO5A, PRKG1, GSTCD, and RTN1 genes (P &lt; 0.0001). MYO5A had an effect of 0.74 on the trait heat tolerance in the studied population. It produces a protein that is widely distributed in the melanin-producing neural crest of the skin. Genetic association between genetic and phenotypic variations showed that OAR1 18300122.1, located in ST3GAL3, had the greatest positive effect on heat tolerance. GWAS analysis identified SNPs associated with heat tolerance in the PLCB1, STEAP3, KSR2, UNC13C , PEBP4, and GPAT2 genes.本研究于2009年至2019年间在埃及的三个干热农业生态区开展，分别为西部沙漠沿海区、新谷沙漠绿洲区以及干热的上埃及地区。本研究在上述三类区域内选取了三个当地绵羊品种：巴尔基（Barki，83头母羊）、瓦哈提（Wahati，55头母羊）与赛义迪（Saidi，68头母羊）。试验期间，羊只处于自然热应激环境下，模拟贫瘠牧场上的夏季放牧场景。研究人员测定并记录了气象与生理参数，并基于羊只对五项核心生理参数的响应（评分范围0至5）计算个体耐热指数，以此区分高耐热与低耐热个体。随后提取DNA样本用于基因组分析。遗传多样性分析结果显示，品种与地理位置对种群均存在显著影响，且品种的影响程度更高。近交分析表明，沙漠品种（瓦哈提与巴尔基）的近交系数低于城镇品种赛义迪。较高的亚群聚类比例提示，在近交压力下存在亚种群分化过程。瓦哈提与巴尔基为特征鲜明的纯种，遗传鉴定性强，而赛义迪品种存在与其他品种的杂交情况。与耐热性状显著关联的单核苷酸多态性（Single Nucleotide Polymorphism, SNP）位点分布于MYO5A、PRKG1、GSTCD与RTN1基因（P < 0.0001），其中MYO5A对试验种群的耐热性状效应值为0.74，其编码的蛋白质广泛分布于皮肤黑色素生成神经嵴中。遗传变异与表型变异的关联分析显示，位于ST3GAL3基因内的OAR1 18300122.1位点对耐热性具有最大的正向效应。全基因组关联分析（Genome-Wide Association Study, GWAS）还在PLCB1、STEAP3、KSR2、UNC13C、PEBP4与GPAT2基因中鉴定出与耐热性相关的SNP位点。