Data from: Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis

Tuberculosis caused by Mycobacterium bovis is a re- emerging disease of livestock which is of major economic importance world-wide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine tuberculosis (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive versus skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina Bovine HD 700K bead chip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, in protein tyrosine phosphatase receptor T (PTPRT; P=4.8 x 10-7) and myosin IIIB (MYO3B; P=5.4. x 10-6). We estimated that 21% of the phenotypic variance in tuberculosis resistance could be explained by all of the informative SNPs, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant (CNV) in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.由牛分枝杆菌（Mycobacterium bovis）引发的结核病是一种再现性家畜疫病，在全球范围内造成显著经济损失，同时还存在人畜共患病风险。乳用牛对牛结核病（bTB）的抗性具有显著遗传力。为鉴定牛结核病的抗性位点，本研究对来自病例牛群的592头荷斯坦-弗里生奶牛病例与559头年龄匹配的对照个体开展了全基因组关联研究。病例与对照分别被划分为明确的表型：多次检测均为皮试阳性且存在病变，以及多次皮试均为阴性。所有个体均采用Illumina牛高密度700K基因分型芯片（Illumina Bovine HD 700K bead chip）进行基因分型。通过基于线性与logistic混合模型及回归的全基因组快速关联分析（GRAMMAR）、区域遗传力定位（RHM）以及单倍型共享分析，本研究在蛋白酪氨酸磷酸酶受体T（PTPRT；P=4.8×10^-7）和肌球蛋白IIIB（MYO3B；P=5.4×10^-6）基因区域内，鉴定出两个达到染色体水平显著性的新型抗性位点。本研究估算发现，所有信息性单核苷酸多态性（SNP）可解释牛结核病抗性表型方差的21%，其中包含PTPRT基因的区域可解释6.2%的方差，而MYO3B基因区域内的疑似拷贝数变异（CNV）可额外解释3.6%的方差。本研究结果加深了学界对宿主感染控制过程中遗传变异机制的理解，同时提示基于遗传标记开展牛结核病抗性选择，有望为牛结核病防控作出重大贡献。