Zehu Yuan1,2,3, Bolormaa Sunduimijid2, Ruidong Xiang2,4, Ralph Behrendt5, Matthew I Knight5, Brett A Mason2, Coralie M Reich2, Claire Prowse-Wilkins2, Christy J Vander Jagt2, Amanda J Chamberlain2, Iona M MacLeod2, Fadi Li1, Xiangpeng Yue6, Hans D Daetwyler7,8. 1. 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. 2. Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, VIC, 3083, Australia. 3. Institutes of Agricultural Science and Technology Development (Joint International Research Laboratory of Agriculture & Agri-Product Safety), Yangzhou University, Yangzhou, 225000, People's Republic of China. 4. Faculty of Veterinary & Agricultural Science, University of Melbourne, Parkville, VIC, 3010, Australia. 5. Agriculture Victoria, Hamilton Centre, Hamilton, VIC, 3300, Australia. 6. 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. lexp@lzu.edu.cn. 7. Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, VIC, 3083, Australia. hans.daetwyler@agriculture.vic.gov.au. 8. School of Applied Systems Biology, La Trobe University, Bundoora, VIC, 3083, Australia. hans.daetwyler@agriculture.vic.gov.au.
Abstract
BACKGROUND: 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. RESULTS: Whereas a relatively small number of molecular phenotypes were significantly heritable (h2 > 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. CONCLUSIONS: 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.
BACKGROUND: 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. RESULTS: Whereas a relatively small number of molecular phenotypes were significantly heritable (h2 > 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. CONCLUSIONS: 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.
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