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牛结核病感染的方差分量和多品种全基因组关联分析,使用了推断的全基因组序列数据。

Variance components for bovine tuberculosis infection and multi-breed genome-wide association analysis using imputed whole genome sequence data.

机构信息

Teagasc, Animal and Grassland Research and Innovation Centre, Moorepark, Fermoy, Co. Cork, Ireland.

School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

出版信息

PLoS One. 2019 Feb 14;14(2):e0212067. doi: 10.1371/journal.pone.0212067. eCollection 2019.

DOI:10.1371/journal.pone.0212067
PMID:30763354
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6375599/
Abstract

Bovine tuberculosis (bTB) is an infectious disease of cattle generally caused by Mycobacterium bovis, a bacterium that can elicit disease humans. Since the 1950s, the objective of the national bTB eradication program in Republic of Ireland was the biological extinction of bTB; that purpose has yet to be achieved. Objectives of the present study were to develop the statistical methodology and variance components to undertake routine genetic evaluations for resistance to bTB; also of interest was the detection of regions of the bovine genome putatively associated with bTB infection in dairy and beef breeds. The novelty of the present study, in terms of research on bTB infection, was the use of beef breeds in the genome-wide association and the utilization of imputed whole genome sequence data. Phenotypic bTB data on 781,270 animals together with imputed whole genome sequence data on 7,346 of these animals' sires were available. Linear mixed models were used to quantify variance components for bTB and EBVs were validated. Within-breed and multi-breed genome-wide associations were undertaken using a single-SNP regression approach. The estimated genetic standard deviation (0.09), heritability (0.12), and repeatability (0.30) substantiate that genetic selection help to eradicate bTB. The multi-breed genome-wide association analysis identified 38 SNPs and 64 QTL regions associated with bTB infection; two QTL regions (both on BTA23) identified in the multi-breed analysis overlapped with the within-breed analyses of Charolais, Limousin, and Holstein-Friesian. Results from the association analysis, coupled with previous studies, suggest bTB is controlled by an infinitely large number of loci, each having a small effect. The methodology and results from the present study will be used to develop national genetic evaluations for bTB in the Republic of Ireland. In addition, results can also be used to help uncover the biological architecture underlying resistance to bTB infection in cattle.

摘要

牛结核病(bTB)是一种传染性疾病,通常由分枝杆菌引起,这种细菌也能使人类患病。自 20 世纪 50 年代以来,爱尔兰共和国国家 bTB 根除计划的目标是实现 bTB 的生物灭绝;但这一目标尚未实现。本研究的目的是开发统计方法和方差分量,以对 bTB 抗性进行常规遗传评估;同时,本研究还关注检测与奶牛和肉牛品种 bTB 感染相关的牛基因组区域。本研究在 bTB 感染研究方面的新颖之处在于使用肉牛品种进行全基因组关联分析,以及利用已推测的全基因组序列数据。共有 781270 头动物的 bTB 表型数据和 7346 头动物的估计全基因组序列数据可用。采用线性混合模型量化 bTB 的方差分量,并验证 EBV。利用单 SNP 回归方法进行了品种内和多品种全基因组关联分析。估计的遗传标准差(0.09)、遗传力(0.12)和可重复性(0.30)证实,遗传选择有助于根除 bTB。多品种全基因组关联分析确定了与 bTB 感染相关的 38 个 SNP 和 64 个 QTL 区域;多品种分析中确定的两个 QTL 区域(均位于 BTA23 上)与夏洛来牛、利木赞牛和荷斯坦-弗里生牛的品种内分析重叠。关联分析的结果与之前的研究表明,bTB 由无数个具有小效应的基因座控制。本研究的方法和结果将用于开发爱尔兰共和国的国家 bTB 遗传评估。此外,这些结果还可以用于帮助揭示牛对 bTB 感染的抗性的生物学结构。

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