DataSheet1_Genetic Variation and the Distribution of Variant Types in the Horse.docx

Genetic variation is a key contributor to health and disease. Understanding the link between an individual’s genotype and the corresponding phenotype is a major goal of medical genetics. Whole genome sequencing (WGS) within and across populations enables highly efficient variant discovery and elucidation of the molecular nature of virtually all genetic variation. Here, we report the largest catalog of genetic variation for the horse, a species of importance as a model for human athletic and performance related traits, using WGS of 534 horses. We show the extent of agreement between two commonly used variant callers. In data from ten target breeds that represent major breed clusters in the domestic horse, we demonstrate the distribution of variants, their allele frequencies across breeds, and identify variants that are unique to a single breed. We investigate variants with no homozygotes that may be potential embryonic lethal variants, as well as variants present in all individuals that likely represent regions of the genome with errors, poor annotation or where the reference genome carries a variant. Finally, we show regions of the genome that have higher or lower levels of genetic variation compared to the genome average. This catalog can be used for variant prioritization for important equine diseases and traits, and to provide key information about regions of the genome where the assembly and/or annotation need to be improved.

遗传变异是健康与疾病的关键因素。解析个体基因型与其相应表型之间的联系是医学遗传学的主要目标。在种群内部及种群之间进行全基因组测序（WGS）能够实现高效的变异发现，并阐明几乎所有遗传变异的分子本质。在此，我们报告了迄今为止最大的马匹遗传变异目录，马作为人类运动和性能相关特征的模型物种具有重要意义，该目录通过全基因组测序分析了534匹马。我们展示了两种常用变异检测工具之间的吻合程度。在代表家马主要品种集群的十个目标品种的数据中，我们展示了变异的分布、各品种间的等位基因频率，并识别了单一品种特有的变异。我们研究了无纯合子的变异，这些变异可能是潜在的胚胎致死变异，以及存在于所有个体中的变异，这些变异可能代表基因组中的错误区域、注释不良的区域，或者参考基因组携带变异的区域。最后，我们展示了相较于基因组平均水平，具有更高或更低遗传变异水平的基因组区域。此目录可用于对重要马匹疾病和特征的变异进行优先排序，并为基因组组装和/或注释需要改进的区域提供关键信息。