Recent advances in high-throughput sequencing technologies provide opportunities to gain novel insights into the genetic basis of phenotypic trait variation. Yet to date, progress in our understanding of genotype-phenotype associations in nonmodel organisms in general and natural vertebrate populations in particular has been hampered by small sample sizes typically available for wildlife populations and a resulting lack of statistical power, as well as a limited ability to control for false-positive signals. Here we propose to combine a genome-wide association study (GWAS) and FST -based approach with population-level replication to partly overcome these limitations. We present a case study in which we used this approach in combination with genotyping-by-sequencing (GBS) single nucleotide polymorphism (SNP) data to identify genomic regions associated with Borrelia afzelii resistance or susceptibility in the natural rodent host of this Lyme disease-causing spirochete, the bank vole (Myodes glareolus). Using this combined approach we identified four consensus SNPs located in exonic regions of the genes Slc26a4, Tns3, Wscd1 and Espnl, which were significantly associated with the voles' Borrelia infectious status within and across populations. Functional links between host responses to bacterial infections and most of these genes have previously been demonstrated in other rodent systems, making them promising new candidates for the study of evolutionary host responses to Borrelia emergence. Our approach is applicable to other systems and may facilitate the identification of genetic variants underlying disease resistance or susceptibility, as well as other ecologically relevant traits, in wildlife populations.

中文翻译：

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结合全基因组关联研究和基于FST的方法来鉴定天然啮齿动物宿主中疏螺旋体介导的选择目标。

高通量测序技术的最新进展为了解表型性状变异的遗传基础提供了新的机会。迄今为止，由于对野生动物种群通常可用的小样本量以及缺乏统计能力以及能力有限，阻碍了我们对一般和天然脊椎动物种群中非模式生物的基因型-表型关联的理解的进展。控制假阳性信号。在这里，我们建议将全基因组关联研究（GWAS）和基于FST的方法与群体水平的复制相结合，以部分克服这些局限性。我们提供了一个案例研究，其中我们将此方法与按序列进行基因分型（GBS）单核苷酸多态性（SNP）数据结合使用，以确定与该莱姆病的天然啮齿动物宿主中的非洲疏螺旋体抗药性或敏感性相关的基因组区域，引起螺旋体，岸田鼠（Myodes glareolus）。使用这种组合方法，我们确定了位于基因Slc26a4，Tns3，Wscd1和Espnl的外显子区域的四个共有SNP，它们与田鼠在种群内和种群之间的疏螺旋体感染状况显着相关。先前已经在其他啮齿动物系统中证明了宿主对细菌感染的反应与大多数这些基因之间的功能联系，这使其成为有前景的研究对博雷利亚菌出现的进化宿主反应的新候选者。