Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle
Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle
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DOI：
10.1073/pnas.0913006107
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发表时间：
2009-12
期刊：
影响因子：
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通讯作者：
C. Seabury;Paul M. Seabury;J. Decker;R. Schnabel;Jeremy F. Taylor;J. Womack
中科院分区：
文献类型：
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作者：
C. Seabury;Paul M. Seabury;J. Decker;R. Schnabel;Jeremy F. Taylor;J. Womack
Toll样受体（TLR）和肽聚糖识别蛋白1（PGLYRP 1）基因在哺乳动物的先天免疫系统中起关键作用。虽然TLR识别各种入侵病原体并诱导先天免疫应答，但PGLYRP 1直接杀微生物。我们使用定制的等位基因特异性测定法对37个牛品种的220个双等位基因变体进行基因分型和验证，其中包括11个牛先天免疫基因（TLR 1-TLR 10，PGLYRP 1）中的54个非同义SNP。贝叶斯单倍型重建和中位数连接网络揭示了普通牛和普通牛indicus品种在每个位点的单倍型共享，我们无法区分专门的B。t.金牛牛和奶牛品种，尽管平均多态性密度为每219 bp一个基因座。99个tagSNPs和一个标签插入-缺失多态性足以预测所有11个先天免疫位点的变异在两个亚种和它们的杂交种，而58个tagSNPs捕获100%的变异在172个位点的B。t.金牛座。PolyPhen和SIFT分析编码氨基酸替换的非同义SNP表明，这些替换中的大多数是良性的，但预计高达31%可能影响蛋白质功能。几个基于多样性的测试提供了强大的纯化选择作用于B中的TLR 10的支持。t.金牛座牛这些结果将广泛影响与牛翻译基因组学相关的工作。
The Toll-like receptor (TLR) and peptidoglycan recognition protein 1 (PGLYRP1) genes play key roles in the innate immune systems of mammals. While the TLRs recognize a variety of invading pathogens and induce innate immune responses, PGLYRP1 is directly microbicidal. We used custom allele-specific assays to genotype and validate 220 diallelic variants, including 54 nonsynonymous SNPs in 11 bovine innate immune genes (TLR1-TLR10, PGLYRP1) for 37 cattle breeds. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and we were unable to differentiate between the specialized B. t. taurus beef and dairy breeds, despite an average polymorphism density of one locus per 219 bp. Ninety-nine tagSNPs and one tag insertion-deletion polymorphism were sufficient to predict 100% of the variation at all 11 innate immune loci in both subspecies and their hybrids, whereas 58 tagSNPs captured 100% of the variation at 172 loci in B. t. taurus. PolyPhen and SIFT analyses of nonsynonymous SNPs encoding amino acid replacements indicated that the majority of these substitutions were benign, but up to 31% were expected to potentially impact protein function. Several diversity-based tests provided support for strong purifying selection acting on TLR10 in B. t. taurus cattle. These results will broadly impact efforts related to bovine translational genomics.