Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.
Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis.
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DOI：
10.1038/hdy.2013.137
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发表时间：
2014-05
期刊：
影响因子：
3.8
通讯作者：
Glass, E. J.
中科院分区：
文献类型：
--
作者：
Bermingham, M. L.;Bishop, S. C.;Woolliams, J. A.;Pong-Wong, R.;Allen, A. R.;McBride, S. H.;Ryder, J. J.;Wright, D. M.;Skuce, R. A.;McDowell, S. W. J.;Glass, E. J.
由牛分枝杆菌引起的结核病是一种再次出现的牲畜疾病，在世界范围内具有重要的经济意义，也是一种人畜共患风险。奶牛宿主对牛结核病（bTB）的抗性具有显著的遗传力。为了确定bTB的耐药位点，我们对来自病例群的592例雌性荷斯坦-弗里塞斯牛和559例年龄匹配的对照进行了全基因组关联研究。病例和对照组被分为不同的表型：分别在多次皮肤试验和病变阳性与皮肤试验阴性。这些动物用Illumina BovineHD 700K头芯片进行基因分型。使用线性和逻辑混合模型和回归（GRAMMAR）、区域遗传力定位（RHM）和单倍型共享分析进行全基因组快速关联，确定了两个具有染色体意义的新抗性位点，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）。我们估计，结核病耐药性中21%的表型变异可以用所有信息丰富的单核苷酸多态性来解释，其中包含PTPRT基因的区域占变异的6.2%，另外3.6%与MYO3B中假定的拷贝数变异有关。这项研究的结果增加了我们对宿主控制感染变异的理解，并表明基于遗传标记的bTB抗性选择有可能对bTB的控制做出重大贡献。
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (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 vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. 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, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10−7) and myosin IIIB (MYO3B; P=5.4 × 10−6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, 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 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.
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影响因子：
3.5
作者：
Bermingham, M. L.;More, S. J.;Berry, D. P.
通讯作者：
Berry, D. P.
影响因子：
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作者：
Bermingham, M. L.;More, S. J.;Berry, D. P.
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Berry, D. P.
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Humblet MF;Boschiroli ML;Saegerman C
通讯作者：
Saegerman C
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通讯作者：
Altshuler, D
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通讯作者：
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