Use of a natural hybrid zone for genome-wide association mapping of craniofacial traits in the house mouse

The identification of the genes involved in morphological variation in nature is still a major challenge. Here we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~145K SNPs) to identify loci underlying craniofacial shape variation. Due to the long history of recombination in the hybrid zone, high mapping resolution is anticipated. The combination of genomes from subspecies allows the mapping of both, variation within subspecies and intersubspecific differences, thereby increasing the overall amount of causal genetic variation than can be detected. Skull and mandible shape were measured using 3D landmarks and geometric morphometrics. Using principle component axes as phenotypes, and a linear mixed model accounting for genetic relatedness in the mapping populations, we identified 9 genomic regions associated with skull and 10 with mandib...

鉴定自然状态下参与形态变异的基因仍是当前的核心挑战之一。本研究探索了一种全新研究策略：我们整合了小家鼠（Mus musculus domesticus与Mus musculus musculus）两个亚种间自然杂交带的178份样本，以及高覆盖度基因组数据（约145K个单核苷酸多态性位点（Single Nucleotide Polymorphism, SNP）），以定位调控颅面形态变异的遗传位点。鉴于该杂交带中长期存在的重组历史，本研究预期可获得较高的遗传定位分辨率。通过结合两个亚种的基因组，我们既可定位亚种内部的形态变异，也可解析亚种间的表型差异，由此相比单一亚种的研究设计，能够检测到更多的因果遗传变异。本研究采用三维地标（3D landmarks）与几何形态测量学（geometric morphometrics）对颅骨与下颌骨形态进行量化；以主成分轴作为表型变量，并采用线性混合模型（linear mixed model）校正定位群体中的遗传亲缘关系，最终鉴定出9个与颅骨形态相关的基因组区域，以及10个与下颌骨形态相关的区域……