Dataset Information

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 (?DAF). 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.

SUBMITTER: Dong K

PROVIDER: S-EPMC7670677 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Dong Kunzhe K Yang Min M Han Jiangang J Ma Qing Q Han Jilong J Song Ziyi Z Luosang Cuicheng C Gorkhali Neena Amatya NA Yang Bohui B He Xiaohong X Ma Yuehui Y Jiang Lin L

BMC genomics 20201117 1

<h4>Background</h4>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.<h4>Results</h4>To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representi ...[more]

PMID: 33203382

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Project description:The fat tail is a phenotype that divides indigenous Iranian sheep genetic resources into two major groups. The objective of the present study is to refine the map location of candidate regions associated with fat deposition, obtained via two separate whole genome scans contrasting thin and fat tail breeds, and to determine the nature of the selection occurring in these regions using a hitchhiking approach. Zel (thin tail) and Lori-Bakhtiari (fat tail) breed samples that had previously been run on the Illumina Ovine 50 k BeadChip, were genotyped with a denser set of SNPs in the three candidate regions using a Sequenom Mass ARRAY platform. Statistical tests were then performed using different and complementary methods based on either site frequency (FST and Median homozygosity) or haplotype (iHS and XP-EHH). The results from candidate regions on chromosome 5 and X revealed clear evidence of selection with the derived haplotypes that was consistent with selection to near fixation for the haplotypes affecting fat tail size in the fat tail breed. An analysis of the candidate region on chromosome 7 indicated that selection differentiated the beneficial alleles between breeds and homozygosity has increased in the thin tail breed which also had the ancestral haplotype. These results enabled us to confirm the signature of selection in these regions and refine the critical intervals from 113 kb, 201 kb, and 2831 kb to 28 kb, 142 kb, and 1006 kb on chromosome 5, 7, and X respectively. These regions contain several genes associated with fat metabolism or developmental processes consisting of TCF7 and PPP2CA (OAR5), PTGDR and NID2 (OAR7), AR, EBP, CACNA1F, HSD17B10,SLC35A2, BMP15, WDR13, and RBM3 (OAR X), and each of which could potentially be the actual target of selection. The study of core haplotypes alleles in our regions of interest also supported the hypothesis that the first domesticated sheep were thin tailed, and that fat tail animals were developed later. Overall, our results provide a comprehensive assessment of how and where selection has affected the patterns of variation in candidate regions associated with fat deposition in thin and fat tail sheep breeds.

Project description:BackgroundThe importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations. Sheep production system is extensive and generally carried out in traditional systems without intensive systematic breeding programmes for high uniform trait production (carcass, wool and milk yield). Therefore, eight indigenous Croatian sheep breeds from eastern Adriatic treated here as metapopulation (EAS), are generally considered as multipurpose breeds (milk, meat and wool), not specialised for a particular type of production, but known for their robustness and resistance to certain environmental conditions. Our objective was to identify genomic regions and genes that exhibit patterns of positive selection signatures, decipher their biological and productive functionality, and provide a "genomic" characterization of EAS adaptation and determine its production type.ResultsWe identified positive selection signatures in EAS using several methods based on reduced local variation, linkage disequilibrium and site frequency spectrum (eROHi, iHS, nSL and CLR). Our analyses identified numerous genomic regions and genes (e.g., desmosomal cadherin and desmoglein gene families) associated with environmental adaptation and economically important traits. Most candidate genes were related to meat/production and health/immune response traits, while some of the candidate genes discovered were important for domestication and evolutionary processes (e.g., HOXa gene family and FSIP2). These results were also confirmed by GO and QTL enrichment analysis.ConclusionsOur results contribute to a better understanding of the unique adaptive genetic architecture of EAS and define its productive type, ultimately providing a new opportunity for future breeding programmes. At the same time, the numerous genes identified will improve our understanding of ruminant (sheep) robustness and resistance in the harsh and specific Mediterranean environment.

Dataset Information

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

Publications

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

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