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Genome wide association study for the identification of genes associated with tail fat deposition in Chinese sheep breeds.

ABSTRACT: Chinese indigenous sheep can be classified into three types based on tail morphology: fat-tailed, fat-rumped, and thin-tailed sheep, of which the typical breeds are large-tailed Han sheep, Altay sheep, and Tibetan sheep, respectively. To unravel the molecular genetic basis underlying the phenotypic differences among Chinese indigenous sheep with these three different tail types, we used ovine high-density 600K single nucleotide polymorphism (SNP) arrays to detect genome-wide associations, and performed general linear model analysis to identify candidate genes, using genotyping technology to validate the candidate genes. Tail type is an important economic trait in sheep. However, the candidate genes associated with tail type are not known. The objective of this study was to identify SNP markers, genes, and chromosomal regions related to tail traits. We performed a genome-wide association study (GWAS) using data from 40 large-tailed Han sheep, 40 Altay sheep (cases) and 40 Tibetan sheep (controls). A total of 31 significant (P<0.05) SNPs associated with tail-type traits were detected. For significant SNPs' loci, we determined their physical location and performed a screening of candidate genes within each region. By combining information from previously reported and annotated biological functional genes, we identified SPAG17, Tbx15, VRTN, NPC2, BMP2 and PDGFD as the most promising candidate genes for tail-type traits. Based on the above identified candidate genes for tail-type traits, BMP2 and PDGFD genes were selected to investigate the relationship between SNPs within the tails in the Altay and Tibetan populations. rs119 T>C in exon1 of the BMP2 gene and one SNP in exon4 (rs69 C>A) of the PDGFD gene were detected. rs119 was of the TT genotype in Altay sheep, while it was of the CC genotype in Tibetan sheep. On rs69 of the PDGFD gene, Altay sheep presented with the CC genotype; however, Tibetan sheep presented with the AA genotype.

SUBMITTER: Zhu C

PROVIDER: S-EPMC8186729 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Variations in body weight and in the distribution of body fat are associated with feed availability, thermoregulation, and energy reserve. Ethiopia is characterized by distinct agro-ecological and human ethnic farmer diversity of ancient origin, which have impacted on the variation of its indigenous livestock. Here, we investigate autosomal genome-wide profiles of 11 Ethiopian indigenous sheep populations using the Illumina Ovine 50 K SNP BeadChip assay. Sheep from the Caribbean, Europe, Middle East, China, and western, northern and southern Africa were included to address globally, the genetic variation and history of Ethiopian populations. Population relationship and structure analysis separated Ethiopian indigenous fat-tail sheep from their North African and Middle Eastern counterparts. It indicates two main genetic backgrounds and supports two distinct genetic histories for African fat-tail sheep. Within Ethiopian sheep, our results show that the short fat-tail sheep do not represent a monophyletic group. Four genetic backgrounds are present in Ethiopian indigenous sheep but at different proportions among the fat-rump and the long fat-tail sheep from western and southern Ethiopia. The Ethiopian fat-rump sheep share a genetic background with Sudanese thin-tail sheep. Genome-wide selection signature analysis identified eight putative candidate regions spanning genes influencing growth traits and fat deposition (NPR2, HINT2, SPAG8, INSR), development of limbs and skeleton, and tail formation (ALX4, HOXB13, BMP4), embryonic development of tendons, bones and cartilages (EYA2, SULF2), regulation of body temperature (TRPM8), body weight and height variation (DIS3L2), control of lipogenesis and intracellular transport of long-chain fatty acids (FABP3), the occurrence and morphology of horns (RXFP2), and response to heat stress (DNAJC18). Our findings suggest that Ethiopian fat-tail sheep represent a uniquely admixed but distinct genepool that presents an important resource for understanding the genetic control of skeletal growth, fat metabolism and associated physiological processes.

Project description:Fat tail in sheep presents a valuable energy reserve that has historically facilitated adaptation to harsh environments. However, in modern intensive and semi-intensive sheep industry systems, breeds with leaner tails are more desirable. In the present study, RNA sequencing (RNA-Seq) was applied to determine the transcriptome profiles of tail fat tissues in two Chinese sheep breeds, fat-rumped Altay sheep and thin-tailed Xinjiang fine wool (XFW) sheep, with extreme fat tail phenotype difference. Then the differentially expressed genes (DEGs) and their sequence variations were further analyzed. In total, 21,527 genes were detected, among which 3,965 displayed significant expression variations in tail fat tissues of the two sheep breeds (P < 0.05), including 707 upregulated and 3,258 downregulated genes. Gene Ontology (GO) analysis disclosed that 198 DEGs were related to fat metabolism. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority of DEGs were significantly enriched in "adipocytokine signaling," "PPAR signaling," and "metabolic pathways" (P < 0.05); moreover, some genes were involved in multiple pathways. Among the 198 DEGs, 22 genes were markedly up- or downregulated in tail fat tissue of Altay sheep, indicating that these genes might be closely related to the fat tail trait of this breed. A total of 41,724 and 42,193 SNPs were detected in the transcriptomic data of tail fat tissues obtained from Altay and XFW sheep, respectively. The distribution of seven SNPs in the coding regions of the 22 candidate genes was further investigated in populations of three sheep breeds with distinct tail phenotypes. In particular, the g.18167532T/C (Oar_v3.1) mutation of the ATP-binding cassette transporter A1 (ABCA1) gene and g.57036072G/T (Oar_v3.1) mutation of the solute carrier family 27 member 2 (SLC27A2) gene showed significantly different distributions and were closely associated with tail phenotype (P < 0.05). The present study provides transcriptomic evidence explaining the differences in fat- and thin-tailed sheep breeds and reveals numerous DEGs and SNPs associated with tail phenotype. Our data provide a valuable theoretical basis for selection of lean-tailed sheep breeds.

Project description:An essential tissue involved in the development and regulation of lipid metabolism in animals is adipose tissue. The “fat-tail” can supply energy for sheep during migration and winter when a low amount of dry matter intake is available. Tail fat content affects meat quality and varies significantly among the different breeds of sheep. Ghezel (fat-tailed) and Zel (thin-tailed) are two important local Iranian sheep breeds that show different patterns of fat storage. The current study presents the transcriptome characterization of tail fat using RNA-sequencing in order to get a better comprehension of the molecular mechanism of lipid storage in the two sheep breeds. The results of sequencing were analyzed with bioinformatics methods, including differentially expressed genes (DEGs) identification, functional enrichment analysis, structural classification of proteins, protein–protein interaction (PPI), network analysis and module analysis. The results revealed a total of332 DEGs between the Zel and Ghezel breed, with78 up-regulated and 254 down-regulated DEGs in the Zel breed. Identification of differential genes showed that some DEGs, such as IL-6, LIPG, SAA1, SOCS3 and HIF-1α, with the largest fold change had close association with lipid deposition. Also, important lipid storage genes such as FASN and SCPEP1 had high levels of expression. Furthermore, functional enrichment analysis revealed some pathways associated with fat deposition, such as “Fatty acid metabolism”, “Fatty acid biosynthesis” and“HIF-1 signaling pathway”. In addition, structural classification of proteins showed major DEGs in transcription factor classes such as JUNB, NR4A3, FOSL1, MAFF, NR4A1, CREB3L1 and ATF3 were up-regulated in the Zel breed. IL-6, JUNB, and related DEGs were up-regulated in the PPI network.HMGCS1, SUCLA2 and STT3B and related DEGs were down-regulated in the PPI network and had high topology scores as hub genes. This implies the DEGs of these modules are important candidate genes for tail fat metabolism and, therefore, can be further studied.

Project description:BACKGROUND:The level of fat deposition in carcass is a crucial factor influencing meat quality. Guangling Large-Tailed (GLT) and Small-Tailed Han (STH) sheep are important local Chinese fat-tailed breeds that show distinct patterns of fat depots. To gain a better understanding of fat deposition, transcriptome profiles were determined by RNA-sequencing of perirenal, subcutaneous, and tail fat tissues from both the sheep breeds. The common highly expressed genes (co-genes) in all the six tissues, and the genes that were differentially expressed (DE genes) between these two breeds in the corresponding tissues were analyzed. RESULTS:Approximately 47 million clean reads were obtained for each sample, and a total of 17,267 genes were annotated. Of the 47 highly expressed co-genes, FABP4, ADIPOQ, FABP5, and CD36 were the four most highly transcribed genes among all the known genes related to adipose deposition. FHC, FHC-pseudogene, and ZC3H10 were also highly expressed genes and could, thus, have roles in fat deposition. A total of 2091, 4233, and 4131 DE genes were identified in the perirenal, subcutaneous, and tail fat tissues between the GLT and STH breeds, respectively. Gene Ontology (GO) analysis showed that some DE genes were associated with adipose metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PPAR signaling pathway and ECM-receptor interaction were specifically enriched. Four genes, namely LOC101102230, PLTP, C1QTNF7, and OLR1 were up-regulated and two genes, SCD and UCP-1, were down-regulated in all the tested tissues of STH. Among the genes involved in ECM-receptor interaction, the genes encoding collagens, laminins, and integrins were quite different depending on the depots or the breeds. In STH, genes such as LAMB3, RELN, TNXB, and ITGA8, were identified to be up regulated and LAMB4 was observed to be down regulated. CONCLUSIONS:This study unravels the complex transcriptome profiles in sheep fat tissues, highlighting the candidate genes involved in fat deposition. Further studies are needed to investigate the roles of the candidate genes in fat deposition and in determining the meat quality of sheep.

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Genome wide association study for the identification of genes associated with tail fat deposition in Chinese sheep breeds.

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