­­­­­­Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

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.

Screening and Joint Analysis of Key lncRNAs for Milk Fat Metabolism in Dairy Cows

“…Moreover, studies have shown that the lack of ENPP2 has a signi cant protective effect on hepatic steatosis [21]. Dong et al [22] found that the expression of PDGFD in adipose tissue of obese individuals was higher than that of lean individuals. In this study, PDGFD was also highly expressed in BMECs with high MFP meanwhile, the downregulated gene KCNMA1 also showed a downregulated trend in white adipose tissue and hypertrophied adipocytes of mice on the high-fat diet [23], which con rmed the reliability of sequencing, suggesting that PDGFD and KCNMA1 genes may play an important role in milk fat metabolism.…”

“…The target genes expression trends are consistent with the DELs that may be targeted and regulated, which is consistent with the general mode of action of lncRNAs on genes [34], and further re ects the accuracy of the sequencing results. It is worth noting that FABP4 is a gene encoding a highly rich fatty acid-binding proteins in the mammary gland, which may have a targeting relationship with TCONS _00082721 and TCONS _00172817 [22]. Among all lncRNAs related to lipid metabolism, TCONS_00082721, TCONS_00119434, TCONS_00191498, TCONS_00007612, TCONS_00118412, and TCONS_00163391 are long intervening/intergenic noncoding RNAs (lincRNAs).…”

“…Since TCONS_00082721 is a differential lincRNA predicted by co-localization and co-expression that may regulate milk fat metabolism, the competitive regulatory relationship between TCONS_00082721_miR-145_FASN and TCONS_00082721_miR-145_TNF will be further studied and cell experiments will be carried out to verify the interaction and function between them. The target gene predicted by TCONS_00172817 is FABP4 [22], which encodes a highly abundant fatty acid-binding protein in the mammary glands of dairy cows. These lncRNAs may regulate milk fat metabolism predicted by the co-localization and co-expression.…”

Exceptional ancient DNA preservation and fibre remains of a Sasanian saltmine sheep mummy in Chehrābād, Iran

“…Hair fibres were examined using scanning electron and light microscopes at USTEM, TU Wien and Austrian Archaeological Institute, respectively. We assessed 51 SNPs in the PDGFD gene associated with the derived fat-tail phenotype [18], using the genotype calls of modern fat and thin-tailed breeds to define the derived allele [43,44]. As the average genome coverage was too low for accurate diploid genotype calls, we report base calls for both alleles.…”

“…This enables characterization of the mummy skin metagenome and population genomic profiling of this sheep in the context of modern breeds. We also genotype 51 SNPs within the first intron of the platelet-derived growth factor D ( PDGFD ) that are highly differentiated between fat-tailed and thin-tailed breeds [18]. Finally we genotype the antisense EIF2S2 retrogene insertion within the 3′ UTR of the IRF2BP2 gene that influences the woolly phenotype and is derived relative to the ancestral coarse ‘hairy’ coat [19], in tandem with fibre analysis using scanning electron microscopy (SEM).…”