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RNA-Seq based genetic variant discovery provides new insights into controlling fat deposition in the tail of sheep.

ABSTRACT: Genetic basis of fat deposition in sheep tail have not been completely elucidated yet. Understanding the genetic mechanisms controlling fat-tail size can improve breeding strategies to modulate fat deposition. RNA sequencing has made it possible to discover genetic variants that may underlie various phenotypic differences. Hence, to identify genetic variants that are important for describing different fat-tail phenotypes in sheep, RNA sequencing was used for single nucleotide polymorphism (SNP) calling in two Iranian sheep breeds (Lori-Bakhtiari, fat-tailed; n?=?4, vs Zel, thin-tailed; n?=?4). Using a stringent pipeline, a total of 112,344 known SNPs were genotyped, of which 30,550 and 42,906 SNPs were shared by at least two Lori-Bakhtiari and Zel, respectively. Comparing these SNPs showed 2,774 (including 209 missense and 25 deleterious SNPs) and 10,470 (including 1,054 missense and 116 deleterious SNPs) breed-specific SNPs in Lori-Bakhtiari and Zel sheep, respectively. Potential breed-specific SNPs were detected by considering those located in QTL regions associated with fatness or reported as important candidates in previous similar studies. Of the breed-specific SNPs, 724 and 2,905 were located in the QTL regions. Functional enrichment analysis of the affected genes revealed several enriched gene ontologies and KEGG pathways related to fat metabolism. Based on the results, several affected genes were proposed to be strongly linked with fat deposition such as DGAT2, ACSL1, ACACA, ADIPOQ, ACLY, FASN, CPT2, SCD, ADCY6, PER3, CSF1R, SLC22A4, GFPT1, CDS2, BMP6, ACSS2, ELOVL6, HOXA10 and FABP4. Moreover, several SNPs were found in the candidate genes related to fatty acid oxidation introducing them as promising candidates responsible for lower fat content in tail of Zel. Our findings provided new insights into the genetic mechanisms of fat deposition in sheep, which can serve to designing appropriate breeding programs.

SUBMITTER: Bakhtiarizadeh MR

PROVIDER: S-EPMC7419499 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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RNA-Seq based genetic variant discovery provides new insights into controlling fat deposition in the tail of sheep.

Bakhtiarizadeh Mohammad Reza MR Alamouti Ali A AA

Scientific reports 20200811 1

Genetic basis of fat deposition in sheep tail have not been completely elucidated yet. Understanding the genetic mechanisms controlling fat-tail size can improve breeding strategies to modulate fat deposition. RNA sequencing has made it possible to discover genetic variants that may underlie various phenotypic differences. Hence, to identify genetic variants that are important for describing different fat-tail phenotypes in sheep, RNA sequencing was used for single nucleotide polymorphism (SNP) ...[more]

PMID: 32782325

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Project description:IntroductionFat-tail in sheep is considered as an important energy reservoir to provide energy as a survival buffer during harsh challenges. However, fat-tail is losing its importance in modern sheep industry systems and thin-tailed breeds are more desirable. Using comparative transcriptome analysis to compare fat-tail tissue between fat- and thin-tailed sheep breeds provides a valuable approach to study the complex genetic factors associated with fat-tail development. However, transcriptomic studies often suffer from issues with reproducibility, which can be improved by integrating multiple studies based on a meta-analysis.MethodsHence, for the first time, an RNA-Seq meta-analysis on sheep fat-tail transcriptomes was performed using six publicly available datasets.Results and discussionA total of 500 genes (221 up-regulated, 279 down-regulated) were identified as differentially expressed genes (DEGs). A jackknife sensitivity analysis confirmed the robustness of the DEGs. Moreover, QTL and functional enrichment analysis reinforced the importance of the DEGs in the underlying molecular mechanisms of fat deposition. Protein-protein interactions (PPIs) network analysis revealed the functional interactions among the DEGs and the subsequent sub-network analysis led to identify six functional sub-networks. According to the results of the network analysis, down-regulated DEGs in green and pink sub-networks (like collagen subunits IV, V, and VI, integrins 1 and 2, SCD, SCD5, ELOVL6, ACLY, SLC27A2, and LPIN1) may impair lipolysis or fatty acid oxidation and cause fat accumulation in tail. On the other hand, up-regulated DEGs, especially those are presented in green and pink sub-networks (like IL6, RBP4, LEPR, PAI-1, EPHX1, HSD11B1, and FMO2), might contribute to a network controlling fat accumulation in the tail of sheep breed through mediating adipogenesis and fatty acid biosynthesis. Our results highlighted a set of known and novel genes/pathways associated with fat-tail development, which could improve the understanding of molecular mechanisms behind fat deposition in sheep fat-tail.

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:BackgroundNowadays, both customers and producers prefer thin-tailed fat sheep. To effectively breed for this phenotype, it is important to identify candidate genes and uncover the genetic mechanism related to tail fat deposition in sheep. Accumulating evidence suggesting that post-transcriptional modification events of precursor-messenger RNA (pre-mRNA), including alternative splicing (AS) and alternative polyadenylation (APA), may regulate tail fat deposition in sheep. Differentially expressed transcripts (DETs) analysis is a way to identify candidate genes related to tail fat deposition. However, due to the technological limitation, post-transcriptional modification events in the tail fat of sheep and DETs between thin-tailed and fat-tailed sheep remains unclear.MethodsIn the present study, we applied pooled PacBio isoform sequencing (Iso-Seq) to generate transcriptomic data of tail fat tissue from six sheep (three thin-tailed sheep and three fat-tailed sheep). By comparing with reference genome, potential gene loci and novel transcripts were identified. Post-transcriptional modification events, including AS and APA, and lncRNA in sheep tail fat were uncovered using pooled Iso-Seq data. Combining Iso-Seq data with six RNA-sequencing (RNA-Seq) data, DETs between thin- and fat-tailed sheep were identified. Protein protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were implemented to investigate the potential functions of DETs.ResultsIn the present study, we revealed the transcriptomic complexity of the tail fat of sheep, result in 9,001 potential novel gene loci, 17,834 AS events, 5,791 APA events, and 3,764 lncRNAs. Combining Iso-Seq data with RNA-Seq data, we identified hundreds of DETs between thin- and fat-tailed sheep. Among them, 21 differentially expressed lncRNAs, such as ENSOART00020036299, ENSOART00020033641, ENSOART00020024562, ENSOART00020003848 and 9.53.1 may regulate tail fat deposition. Many novel transcripts were identified as DETs, including 15.527.13 (DGAT2), 13.624.23 (ACSS2), 11.689.28 (ACLY), 11.689.18 (ACLY), 11.689.14 (ACLY), 11.660.12 (ACLY), 22.289.6 (SCD), 22.289.3 (SCD) and 22.289.14 (SCD). Most of the identified DETs have been enriched in GO and KEGG pathways related to extracellular matrix (ECM). Our result revealed the transcriptome complexity and identified many candidate transcripts in tail fat, which could enhance the understanding of molecular mechanisms behind tail fat deposition.

Dataset Information

RNA-Seq based genetic variant discovery provides new insights into controlling fat deposition in the tail of sheep.

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RNA-Seq based genetic variant discovery provides new insights into controlling fat deposition in the tail of sheep.

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