Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep
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RESEARCH ARTICLE
Open Access
Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep Kunzhe Dong1,2,3†, Min Yang1,2,4†, Jiangang Han1,2†, Qing Ma5, Jilong Han2,4, Ziyi Song6, Cuicheng Luosang7, Neena Amatya Gorkhali1,2, Bohui Yang8, Xiaohong He1,2*, Yuehui Ma1,2* and Lin Jiang1,2*
Abstract Background: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. Results: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. Conclusions: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases. Keywords: PDGFD, Fat-tailed sheep, Genomic scan, Fat deposit, Adipogenesis
Background Following domestication in the Fertile Crescent approximately 8000–9000 years ago [1], sheep spread over a wide geographical range worldwide. To adapt to nutrient-poor diets and extreme environments, sheep develop a substantial variation in many phenotypic traits [2]. One of the main * Correspondence: [email protected]; [email protected]; [email protected] † Kunzhe Dong, Min Yang and Jiangang Han contributed equally to this work. 1 National Germplasm Center of Domestic Animal Resources, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan West Road, Beijing 100193, China Full list of author information is available at the end of the article
morphological changes from wild ancestors is the lengthening of the tail and distinct patterns of tail fat deposition. It is believed that fat-ta
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