Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows.
Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows.
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DOI：
10.1186/s12864-017-3836-x
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发表时间：
2017-06-24
期刊：
影响因子：
4.4
通讯作者：
Glass EJ
中科院分区：
文献类型：
--
作者：
Wilkinson S;Bishop SC;Allen AR;McBride SH;Skuce RA;Bermingham M;Woolliams JA;Glass EJ
牛对牛分枝杆菌感染的易感性部分由宿主遗传学决定。然而，诊断为感染M.牛显示出不同的病理学迹象。宿主对感染反应的变化可能代表自暴露时间以来的连续性或由于不同病原体处理而导致的不同结果。探讨了宿主遗传学与宿主反应变异及感染后病理后遗症的关系。通过对1966头荷斯坦-弗里斯兰奶牛在具有三种不同表型的538，231个SNPs处进行基因分型来探索牛感染。这些问题是：单一皮内宫颈比较结核菌素（SICCT）试验阳性伴可见病变（VL），SICCT阳性伴未检出可见病变（NVL），以及匹配对照SICCT阴性多次。区域遗传力作图在染色体17、22和23上确定了与NVL表型相关的三个位点，与染色体13上与VL表型相关的区域不同。23号染色体上的区域具有全基因组意义，与映射窗口重叠的候选基因包括牛白细胞抗原IIb类区域的成员，这是一种以其在免疫和抗病性中的作用而闻名的复合物。染色体遗传力分析归因于变异的VL和NVL表型，分别为6和13条染色体，这些染色体中的4个被发现解释了VL和NVL表型的表型变异的比例。将M.牛的结果（VL和NVL）方差归因于9条染色体。对比两个M.牛感染结果（VL与NVL）发现9条染色体具有可遗传变异。无论研究中的病例表型如何，染色体遗传率均不超过8%，表明bTB抗性的遗传控制由位于牛基因组许多染色体上的小至中等效应的变体组成。这些结果表明，M.牛感染的结果由不同的和重叠的遗传变异决定。因此，M.牛感染的牛可以部分地由遗传决定，并指示不同的宿主反应或病原体处理。在M之后可能至少有三个不同的结果。奶牛中的牛暴露：对感染的抵抗力、感染导致病理或未检测到病理。本文的在线版本（doi：10.1186/s12864-017-3836-x）包含补充材料，可供授权用户使用。
Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology. The online version of this article (doi:10.1186/s12864-017-3836-x) contains supplementary material, which is available to authorized users.