Imputation to whole-genome sequence is now possible in large sheep populations. It is therefore of interest to use this data in genome-wide association studies (GWAS) to investigate putative causal variants and genes that underpin economically important traits. Merino wool is globally sought after for luxury fabrics, but some key wool quality attributes are unfavourably correlated with the characteristic skin wrinkle of Merinos. In turn, skin wrinkle is strongly linked to susceptibility to “fly strike” (Cutaneous myiasis), which is a major welfare issue. Here, we use whole-genome sequence data in a multi-trait GWAS to identify pleiotropic putative causal variants and genes associated with changes in key wool traits and skin wrinkle. A stepwise conditional multi-trait GWAS (CM-GWAS) identified putative causal variants and related genes from 178 independent quantitative trait loci (QTL) of 16 wool and skin wrinkle traits, measured on up to 7218 Merino sheep with 31 million imputed whole-genome sequence (WGS) genotypes. Novel candidate gene findings included the MAT1A gene that encodes an enzyme involved in the sulphur metabolism pathway critical to production of wool proteins, and the ESRP1 gene. We also discovered a significant wrinkle variant upstream of the HAS2 gene, which in dogs is associated with the exaggerated skin folds in the Shar-Pei breed. The wool and skin wrinkle traits studied here appear to be highly polygenic with many putative candidate variants showing considerable pleiotropy. Our CM-GWAS identified many highly plausible candidate genes for wool traits as well as breech wrinkle and breech area wool cover.

中文翻译：

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条件性多性状序列 GWAS 发现了羊毛、皮肤皱纹和臀盖性状的多效候选基因和变体

现在可以在大型绵羊种群中对全基因组序列进行插补。因此，在全基因组关联研究 (GWAS) 中使用这些数据来研究支持经济重要特征的假定因果变异和基因是很有趣的。美利奴羊毛在全球范围内作为奢华面料备受追捧，但一些关键的羊毛质量属性与美利奴羊特有的皮肤皱纹存在不利关联。反过来，皮肤皱纹与“蝇击”（皮肤蝇蛆病）的易感性密切相关，这是一个主要的福利问题。在这里，我们在多性状 GWAS 中使用全基因组序列数据来识别与关键羊毛性状和皮肤皱纹变化相关的多效性假定因果变异和基因。逐步条件多性状 GWAS (CM-GWAS) 从 16 个羊毛和皮肤皱纹性状的 178 个独立数量性状基因座 (QTL) 中确定了推定的因果变异和相关基因，对多达 7218 只美利奴羊进行了测量，其中有 3100 万个估算的全基因组序列 (WGS) 基因型。新的候选基因发现包括 MAT1A 基因和 ESRP1 基因，该基因编码参与硫代谢途径对羊毛蛋白生产至关重要的酶。我们还在 HAS2 基因上游发现了一个显着的皱纹变异，它在狗中与沙皮犬品种中夸张的皮肤皱褶有关。这里研究的羊毛和皮肤皱纹特征似乎是高度多基因的，许多假定的候选变体显示出相当多的多效性。