Comprehensive RNA-Seq Meta-analysis identifies genes/pathways related to fat-tail development of sheep

Fat-tail content of sheep presents a valuable energy reserve that has historically facilitated adaptation to harshenvironments. However, in modern intensive sheep industry systems, thin-tailed sheep are preferred, becausefat deposition requires a greater energy cost than accretion of an equivalent amount of lean tissue.Comparative transcriptome analysis of thin-tailed against fat-tailed breeds can shed light on the geneticmechanisms controlling fat-tail development and improve breeding strategies to modulate fat deposition.Transcriptomic studies often suffer from issues with reproducibility, which can be improved by integratingmultiple studies based on meta-analysis. Here, an RNA-Seq meta-analysis on the transcriptomes of sixpublicly available datasets was performed. To analyze each study, first, quality control and trimming of theraw reads were done using FastQC and Trimmomatic tools, repectively. Then, the clean reads were alignedagainst reference sheep genome (V۱.۰.۱۰۴). Htseq was employed to quantify the expression levels of thegenes and DESeq۲ R package was used to identify the genes differentially expressed (DEGs) between fatandthin-tailed sheep breeds. The output of the DEGs analysis from all studies was further employed for themeta-analysis based on two approaches (fishercomb and invnorm) from metaRNASeq R package. The genesthat were identified to be DEGs by both approaches were considered as final DEGs. Totally, ۶۵۰,۶۰۵,۲۵۹reads related to ۶ samples were analyzed. A total of ۳۵۳ genes (۱۳۴ upregulated, ۲۱۹ down-regulated) wereidentified as DEGs. Some of these genes including SCD, FASN, ACACA, CPT۲, ACLY, LPL and DGAT۲confirmed the previous reports of associations with fat-tail development. Functional analysis of DEGsshowed ۶۴ KEGG pathways and ۲۴۲۳ GO terms were signiciantly enriched including "fatty acid metabolismpathways", "carbohydrate metabolism" and "steroid biosynthesis” which may contribute to fat storage insheep tails. Our results highlighted a core set of genes/pathways associated with fat-tail development in sheep.

Keywords:

Sheep , Fat tail , Fat deposition , RNA-seq , Meta-analysis