Data from: Using the Mus musculus hybrid zone to assess covariation and genetic architecture of limb bone lengths

Two subspecies of the house mouse, Mus musculus domesticus and Mus musculus musculus, meet in a narrow contact zone across Europe. Mice in the hybrid zone are highly admixed, representing the full range of mixed ancestry from the two subspecies. Given the distinct morphologies of these subspecies, these natural hybrids can be used for genome-wide association mapping at sufficiently high resolution to directly infer candidate genes. We focus here on limb bone length differences, which is of special interest for understanding the evolution of developmentally correlated traits. We used 172 first-generation descendants of wild-caught mice from the hybrid zone to measure the length of stylopod (humerus / femur), zeugopod (ulna / tibia) and autopod (metacarpal / metatarsal) elements in skeletal CT scans. We find phenotypic covariation between limb elements in the hybrids similar to patterns previously described in M. m. domesticus inbred strains, suggesting that the hybrid genotypes do not influence the covariation pattern in a major way. Mapping was performed using 143,592 SNPs and identified several genomic regions associated with length differences in each bone. Each candidate region explains only a small proportion of phenotypic variance, suggesting that bone length is highly polygenic. None of the candidate regions includes the canonical genes known to control embryonic limb development. Instead, we are able to identify candidate genes with known roles in osteoblast differentiation and bone structure determination, as well as recently evolved genes of, as yet, unknown function.家栖小家鼠（Mus musculus domesticus）与小家鼠指名亚种（Mus musculus musculus）这两个小家鼠亚种，在欧洲范围内形成一条狭窄的杂交接触带。该杂交带内的小鼠具有高度的基因组混合特征，涵盖了来自两个亚种的全部谱系混合类型。鉴于这两个亚种具有显著的形态差异，这类天然杂交种群可用于高分辨率全基因组关联分析，以直接推断候选基因。本研究聚焦于四肢骨长度差异，该性状对于理解发育相关性状的演化具有重要研究价值。我们使用172只源自杂交带野生捕获小鼠的第一代后代，通过骨骼CT扫描测量了近肢节（stylopod，肱骨/股骨）、中肢节（zeugopod，尺骨/胫骨）以及远肢节（autopod，掌骨/跖骨）的长度。我们发现杂交种群中四肢骨骼间的表型协同变异模式，与此前在家栖小家鼠（M. m. domesticus）近交系中报道的模式一致，这表明杂交基因型并未对该协同变异模式产生显著影响。本研究使用143592个单核苷酸多态性位点（SNPs）进行关联定位，在每块骨骼的长度差异相关区域中均鉴定出了若干基因组区段。每个候选区段仅能解释一小部分表型变异，这表明骨骼长度性状属于高度多基因调控的性状。所有候选区段均未包含已知的调控胚胎四肢发育的经典基因。与之相反，我们鉴定出的候选基因要么已知在成骨细胞分化及骨骼结构决定中发挥功能，要么属于新近演化出的、目前功能尚未明确的基因。