Yuan Zehu, Sunduimijid Bolormaa, Xiang Ruidong, Behrendt Ralph, Knight Matthew I, Mason Brett A, Reich Coralie M, Prowse-Wilkins Claire, Vander Jagt Christy J, Chamberlain Amanda J, MacLeod Iona M, Li Fadi, Yue Xiangpeng, Daetwyler Hans D
State Key Laboratory of Grassland Agro-ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs; Grassland Agriculture Engineering Center, Ministry of Education; College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, People's Republic of China.
Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, VIC, 3083, Australia.
Genet Sel Evol. 2021 Jan 18;53(1):8. doi: 10.1186/s12711-021-00602-9.
Variants that regulate transcription, such as expression quantitative trait loci (eQTL), have shown enrichment in genome-wide association studies (GWAS) for mammalian complex traits. However, no study has reported eQTL in sheep, although it is an important agricultural species for which many GWAS of complex meat traits have been conducted. Using RNA sequence data produced from liver and muscle from 149 sheep and imputed whole-genome single nucleotide polymorphisms (SNPs), our aim was to dissect the genetic architecture of the transcriptome by associating sheep genotypes with three major molecular phenotypes including gene expression (geQTL), exon expression (eeQTL) and RNA splicing (sQTL). We also examined these three types of eQTL for their enrichment in GWAS of multi-meat traits and fatty acid profiles.
Whereas a relatively small number of molecular phenotypes were significantly heritable (h > 0, P < 0.05), their mean heritability ranged from 0.67 to 0.73 for liver and from 0.71 to 0.77 for muscle. Association analysis between molecular phenotypes and SNPs within ± 1 Mb identified many significant cis-eQTL (false discovery rate, FDR < 0.01). The median distance between the eQTL and transcription start sites (TSS) ranged from 68 to 153 kb across the three eQTL types. The number of common variants between geQTL, eeQTL and sQTL within each tissue, and the number of common variants between liver and muscle within each eQTL type were all significantly (P < 0.05) larger than expected by chance. The identified eQTL were significantly (P < 0.05) enriched in GWAS hits associated with 56 carcass traits and fatty acid profiles. For example, several geQTL in muscle mapped to the FAM184B gene, hundreds of sQTL in liver and muscle mapped to the CAST gene, and hundreds of sQTL in liver mapped to the C6 gene. These three genes are associated with body composition or fatty acid profiles.
We detected a large number of significant eQTL and found that the overlap of variants between eQTL types and tissues was prevalent. Many eQTL were also QTL for meat traits. Our study fills a gap in the knowledge on the regulatory variants and their role in complex traits for the sheep model.
调控转录的变异，如表达数量性状位点（eQTL），在哺乳动物复杂性状的全基因组关联研究（GWAS）中显示出富集现象。然而，尽管绵羊是一种重要的农业物种，已经针对其复杂肉质性状开展了许多GWAS研究，但尚无关于绵羊eQTL的报道。利用149只绵羊肝脏和肌肉产生的RNA序列数据以及估算的全基因组单核苷酸多态性（SNP），我们的目标是通过将绵羊基因型与三种主要分子表型（包括基因表达（geQTL）、外显子表达（eeQTL）和RNA剪接（sQTL））相关联，剖析转录组的遗传结构。我们还研究了这三种类型的eQTL在多肉质性状和脂肪酸谱的GWAS中的富集情况。
虽然相对较少的分子表型具有显著遗传性（h>0，P<0.05），但其平均遗传力在肝脏中为0.67至0.73，在肌肉中为0.71至0.77。分子表型与±1 Mb范围内的SNP之间的关联分析确定了许多显著的顺式eQTL（错误发现率，FDR<0.01）。在三种eQTL类型中，eQTL与转录起始位点（TSS）之间的中位数距离在68至153 kb之间。每个组织内geQTL、eeQTL和sQTL之间的共同变异数量，以及每种eQTL类型中肝脏和肌肉之间的共同变异数量，均显著（P<0.05）大于偶然预期。所鉴定的eQTL在与56种胴体性状和脂肪酸谱相关的GWAS命中结果中显著（P<0.05）富集。例如，肌肉中的几个geQTL映射到FAM184B基因，肝脏和肌肉中的数百个sQTL映射到CAST基因，肝脏中的数百个sQTL映射到C6基因。这三个基因与身体组成或脂肪酸谱相关。
我们检测到大量显著的eQTL，并发现eQTL类型和组织之间的变异重叠很普遍。许多eQTL也是肉质性状的QTL。我们的研究填补了绵羊模型中调控变异及其在复杂性状中的作用方面的知识空白。
