Two mutations at KRT74 and EDAR synergistically drive the fine-wool production in Chinese sheep.

INTRODUCTION: Fine-wool sheep are the most common breed used by the wool industry worldwide. Fine-wool sheep have over a three-fold higher follicle density and a 50% smaller fiber diameter than coarse-wool sheep. OBJECTIVES: This study aims to clarify the underlying genetic basis for the denser and finer wool phenotype in fine-wool breeds. METHOD: Whole-genome sequences of 140 samples, Ovine HD630K SNP array data of 385 samples, including fine, semi-fine, and coarse wool sheep, as well as skin transcriptomes of nine samples were integrated for genomic selection signature analysis. RESULTS: Two loci at keratin 74 (KRT74) and ectodysplasin receptor (EDAR) were revealed. Fine-scale analysis in 250 fine/semi-fine and 198 coarse wool sheep narrowed this association to one C/A missense variant of KRT74 (OAR3:133,486,008, P = 1.02E-67) and one T/C SNP in the regulatory region upstream of EDAR (OAR3:61,927,840, P = 2.50E-43). Cellular over-expression and ovine skin section staining assays confirmed that C-KRT74 activated the KRT74 protein and specifically enlarged cell size at the Huxley's layer of the inner root sheath (P < 0.01). This structure enhancement shapes the growing hair shaft into the finer wool than the wild type. Luciferase assays validated that the C-to-T mutation upregulated EDAR mRNA expression via a newly created SOX2 binding site and potentially led to the formation of more hair placodes. CONCLUSIONS: Two functional mutations driving finer and denser wool production were characterized and offered new targets for genetic breeding during wool sheep selection. This study not only provides a theoretical basis for future selection of fine wool sheep breeds but also contributes to improving the value of wool commodities.

Transcriptome Profiling of Developing Ovine Fat Tail Tissue Reveals an Important Role for MTFP1 in Regulation of Adipogenesis.

Fat-tail sheep exhibit a unique trait whereby substantial adipose tissue accumulates in the tail, a phenotype that is advantageous in many agroecological environments. In this study, we conducted histological assays, transcriptome analysis and functional assays to examine morphogenesis, characterize gene expression, and elucidate mechanisms that regulate fat tail development. We obtained the microstructure of tail before and after fat deposition, and demonstrated that measurable fat deposition occurred by the 80-day embryo (E80) stage, earlier than other tissues. Transcriptome profiling revealed 1,058 differentially expressed genes (DEGs) with six markedly different expression trends. GSEA enrichment and other downstream analyses showed important roles for genes and pathways involving in metabolism and that mitochondrial components were specifically overexpressed in the fat tail tissue of the 70-day embryo (E70). One hundred and eighty-three genes were further identified by leading edge gene analysis, among which, 17 genes have been reported in previous studies, including EEF1D, MTFP1, PPP1CA, PDGFD. Notably, the MTFP1 gene was highly correlated with the expression of other genes and with the highest enrichment score and gene expression change. Knockdown of MTFP1 in isolated adipose derived stem cells (ADSCs) inhibited cell proliferation and migration ability, besides, promoted the process of adipogenesis in vitro.

A study using single-locus and multi-locus genome-wide association study to identify genes associated with teat number in Hu sheep.

The multiple teats trait is common in many species of mammals and is considered related to lactation ability in swine. However, in Hu sheep, related gene research is still relatively limited. In this study, a genome-wide association study was used to identify genetic markers and genes related to the number of teats in the Hu sheep population, a native Chinese sheep breed. A single marker method and several multi-locus methods were utilized. A total of 61 SNPs were found to be related to the number of teats. Among these, 11 SNPs and one SNP were consistently detected by two and three multi-locus models respectively. Four SNPs were concordantly identified between the single marker and multi-locus methods. We also performed quantitative real-time PCR testing of these identified candidate genes, identifying three genes with significantly different expression. Our study suggested that the LHFP, DPYSL2, and TDP-43 genes may be related to the number of teats in sheep. The combination of single and multi-locus GWAS detected additional SNPs not found with only one model. Our results provide new and important insights into the genetic mechanisms of the mammalian multiparous teat phenotype. These findings may be useful for future breeding and understanding the genetics of sheep and other livestock.