Comparative genomics of Toll-like receptor signalling in five species.

Comparative genomics of Toll-like receptor signalling in five species.
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DOI:
10.1186/1471-2164-10-216
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发表时间:
2009-05-11
期刊:
影响因子:
4.4
通讯作者:
Glass EJ
Glass EJ
中科院分区:
生物学2区
文献类型:
--
作者:
Jann OC;King A;Corrales NL;Anderson SI;Jensen K;Ait-Ali T;Tang H;Wu C;Cockett NE;Archibald AL;Glass EJ

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在过去的十年中,一些研究已经确定了影响哺乳动物免疫相关性状变异的数量性状基因座(QTL)。最近对人类和小鼠的研究表明,这种变异的一部分可能是由参与Toll样受体(TLR)信号传导的基因多态性引起的。在这个项目中,我们使用了一种比较的方法来调查TLR相关基因的重要性相比,其他免疫相关基因的抗性性状在五个物种相关联的基因组位置与以前发表的免疫相关的QTL区域。我们报告的TLR 1 -10和10个相关的信号分子在绵羊和猪的基因组定位使用计算机和/或辐射杂交(RH)映射技术,并比较它们的位置与它们的注释同源物在人类,牛和小鼠的全基因组序列。我们还报告了猪8号和13号染色体的中密度RH图谱。对先前发表的相关QTL的位置进行比较分析,可以鉴定与几个物种中相似健康性状相关的同源区域,这些区域包含TLR相关基因和其他免疫相关基因。通过检查相关基因表达和关联研究收集了其他证据。这种比较基因组学方法确定了8个基因作为健康相关性状变异的潜在致病基因。这些包括奶牛对临床乳腺炎的易感性,羊、牛、人和小鼠的一般抗病性,以及牛和小鼠对原生动物感染的耐受性。4个TLR相关基因(TLR 1、6、MyD 88、IRF 3)可能是控制几个物种对相同或相似病原菌抗性的QTL区域的候选基因。需要进一步的研究来调查这些基因内多态性的潜在作用。
Over the last decade, several studies have identified quantitative trait loci (QTL) affecting variation of immune related traits in mammals. Recent studies in humans and mice suggest that part of this variation may be caused by polymorphisms in genes involved in Toll-like receptor (TLR) signalling. In this project, we used a comparative approach to investigate the importance of TLR-related genes in comparison with other immunologically relevant genes for resistance traits in five species by associating their genomic location with previously published immune-related QTL regions. We report the genomic localisation of TLR1-10 and ten associated signalling molecules in sheep and pig using in-silico and/or radiation hybrid (RH) mapping techniques and compare their positions with their annotated homologues in the human, cattle and mouse whole genome sequences. We also report medium-density RH maps for porcine chromosomes 8 and 13. A comparative analysis of the positions of previously published relevant QTLs allowed the identification of homologous regions that are associated with similar health traits in several species and which contain TLR related and other immunologically relevant genes. Additional evidence was gathered by examining relevant gene expression and association studies. This comparative genomic approach identified eight genes as potentially causative genes for variations of health related traits. These include susceptibility to clinical mastitis in dairy cattle, general disease resistance in sheep, cattle, humans and mice, and tolerance to protozoan infection in cattle and mice. Four TLR-related genes (TLR1, 6, MyD88, IRF3) appear to be the most likely candidate genes underlying QTL regions which control the resistance to the same or similar pathogens in several species. Further studies are required to investigate the potential role of polymorphisms within these genes.
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