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Fat tail is one of the most important domesticated characteristics in sheep; however its molecular mechanism is poorly understood. Here we took small-tailed F2 hybrid of wild Argali sheep and typical fat-tailed Bashby sheep as research object. First, histological analysis revealed that the mean diameter and area in tail and subcutaneous fat cells, and surface density in tail fat in Bashby sheep were significantly larger than that in F2 sheep, and surface density of fat in subcutaneous fat in Bashby sheep was significantly lower than that in F2 sheep. Second, 873 differentially expressed genes (DEGs) of tail fat between Bashby and F2 sheep were identified by RNA-seq. Third, the tissue expression profile and relative expression difference between Bashby and F2 sheep of 7 of 873 DEGs were analyzed by RT-PCR. SCD, ESR1, EMR1, PHYH, STAT3 and GPAM genes were highly expressed in fat, muscle and liver, and ALDH1A1 were highly expressed in small intestine. In addition, the expressions of SCD, PHYH and CPAM genes in tail fat of F2 sheep were lower than that of Bashby sheep, while the expression patterns of ESR1 and EMR1 were reversed. Our findings will not only help understand molecular mechanism of fat tail, but also provide theoretical material in sheep evolution., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The identification of genome-wide selection signatures can provide insights on the mechanisms of natural and/or artificial selection and uncover genes related to biological functions and/or phenotypes. Tibetan sheep are an important livestock in Tibet, providing meat and wool for Tibetans who are renown for breeding livestock that adapt well to high altitudes. Using whole-genome sequences with an effective sequencing depth of 5×, we investigated the genomic diversity and structure and, identified selection signatures of White Tibetan, Oula and Poll Dorset sheep. We obtained 30,163,679 Single Nucleotide Polymorphisms (SNPs) and 5,388,372 indels benchmarked against the ovine Oar_v4.0 genome assembly. Next, using F ST , ZHp and XP-EHH approaches, we identified selection signatures spanning a set of candidate genes, including HIF1A, CAPN3, PRKAA1, RXFP2, TRHR and HOXA10 that are associated with pathways and GO categories putatively related to hypoxia responses, meat traits and disease resistance. Candidate genes and GO terms associated with coat color were also identified. Finally, quantification of blood physiological parameters, revealed higher levels of mean corpuscular hemoglobin measurement and mean corpuscular hemoglobin concentration in Tibetan sheep compared with Poll Dorset, suggesting a greater oxygen-carrying capacity in the Tibetan sheep and thus better adaptation to high-altitude hypoxia. In conclusion, this study provides a greater understanding of genome diversity and variations associated with adaptive and production traits in sheep.

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1-5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits ( 5S_rRNA ), the innate and adaptive immune response ( HERC2 and CYFIP1 ), digestion and metabolism ( CENPJ ), growth (SPP1), body size and developments ( GJB2 and GJA3 ). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.

Coat colour is one of the most important economic traits of sheep and is mainly used for breed identification and characterization. This trait is determined by the biochemical function, availability and distribution of phaeomelanin and eumelanin pigments. In our study, we conducted a genome-wide association study to identify candidate genes and genetic variants associated with coat colour in 75 Chinese Tan sheep using the ovine 600K SNP BeadChip. Accordingly, we identified two significant SNPs (rs409651063 at 14.232 Mb and rs408511664 at 14.228 Mb) associated with coat colour in the MC1R gene on chromosome 14 with -log10(P) = 2.47E-14 and 1.00E-13, respectively. The consequence of rs409651063 was a missense variant (g.14231948 G>A) that caused an amino acid change (Asp105Asn); however, the second SNP (rs408511664) was a synonymous substitution and is an upstream variant (g.14228343G>A). Moreover, our PCR analysis revealed that the genotype of white sheep was exclusively homozygous (GG), whereas the genotypes of black-head sheep were mainly heterozygous (GA). Interestingly, allele-specific expression analysis (using the missense variant for the skin cDNA samples from black-head sheep) revealed that only the G allele was expressed in the skin covered with white hair, while both the G and A alleles were expressed in the skin covered with black hair. This finding indicated that the missense mutation that we identified is probably responsible for white coat colour in Tan sheep. Furthermore, qPCR analysis of MC1R mRNA level in the skin samples was significantly higher in black-head than white sheep and very significantly higher in GA than GG individuals. Taken together, these results help to elucidate the genetic mechanism underlying coat colour variation in Chinese indigenous sheep., Competing Interests: The authors have declared that no competing interests exist.

Through long term natural and artificial selection, domestic sheep ( Ovis aries ) have become adapted to a diverse range of agro-ecological environments and display multiple phenotypic traits. Characterization of diversity and selection signature is essential for genetic improvement, understanding of environmental adaptation, as well as utilization and conservation of sheep genetic resources. Here, we aimed to assess genomic diversity, population structure, and genomic selection among five Chinese native sheep breeds using 600K high density SNP genotypes. A total of 96 animals of the five breeds were selected from different geographical locations with extremely dry or humid conditions. We found a high proportion of informative SNPs, ranging from 93.3% in Yabuyi to 95.5% in Wadi, Hu, and Hetian sheep. The average pairwise population differentiation (F ST ) between the breeds was 0.048%, ranging from 0.022% to 0.054%, indicating their low to moderate differentiation. PCA, ADMIXTURE, and phylogenetic tree analyses revealed a clustering pattern of the five Chinese sheep breeds according to their geographical distribution, tail type, coat color, body size, and breeding history. The genomic regions under putative selection identified by F ST and XP-EHH approaches frequently overlapped across the breeds, and spanned genes associated with adaptation to extremely dry or humid environments, innate and adaptive immune responses, and growth, wool, milk, and reproduction traits. The present study offers novel insight into genomic adaptation to dry and humid climates in sheep among other domestic animals and provides a valuable resource for further investigation. Moreover, it contributes useful information to sustainable utilization and conservation of sheep genetic resources.

Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 (Keratinocyte growth factor-7), which was previously reported as a good protective candidate for pulmonary injuries. We further found a SNP upstream of FGF-7 that appears to contribute to the divergence signature. First, the SNP occurred at an extremely conserved site. Second, the SNP showed an increasing allele frequency with the elevated altitude in Nepalese sheep. Third, the electrophoretic mobility shift assays (EMSA) analysis using human lung cancer cells revealed the allele-specific DNA-protein interactions. We thus hypothesized that FGF-7 gene potentially enhances lung function by regulating its expression level in high-altitude sheep through altering its binding of specific transcription factors. Especially, FGF-7 gene was not implicated in previous studies of other high-altitude species, suggesting a potential novel adaptive mechanism to high altitude in sheep at the Himalayas.

The KiSS-1 and GPR54 genes were studied as candidate genes for the prolificacy in sheep. Four pairs of primers were designed to detect single nucleotide polymorphisms of exon 1 of KiSS-1 gene and exon 1, exon 2 and partial exon 5 of GPR54 gene in high fecundity breeds (Small Tail Han and Hu sheep) and low fecundity breeds (Dorset, Texel and Corriedale sheep) by PCR-SSCP. Polymorphisms in exon 1 of KiSS-1 gene were detected in prolific Small Tail Han sheep (AA, AB and BB genotypes) and Hu sheep (AA and CC genotypes), no polymorphism was found in low fecundity sheep breeds (only AA genotype). Polymorphisms in exon 2 of GPR54 gene were detected in prolific Hu sheep (DD and EE genotypes) and no polymorphism was found in prolific Small Tail Han sheep and low fecundity sheep breeds (only DD genotype). No polymorphism was detected in exon 1 and partial exon 5 of GPR54 gene in five sheep breeds. The polymorphic genotypes were sequenced. While compared the BB genotype with the AA genotype, one nucleotide mutation (G1035A) was detected, which resulted in amino acid change, Val25Met. Five nucleotide mutations were detected from AA to CC genotype (C981T, C996T, T997C, C1034G, C1039T), and among them four caused amino acid changes, that is, Arg7Trp, Phe12Leu, Asn24Lys, Ala26Val. While compared the EE genotype with the DD genotype, two nucleotide mutations (T2360C, A2411C) were detected, which gave rise to amino acid changes, Met90Thr and Asp107Ala, respectively. Genotype frequencies of AA, BB and AB were 0.62, 0.05 and 0.33 in Small Tail Han sheep, respectively. The Small Tail Han sheep ewes with genotype BB or AB had 0.88 (P < 0.05) or 0.51 (P < 0.05) lambs more than those with genotype AA; the Small Tail Han sheep ewes with genotype BB had 0.37 (P > 0.05) lambs more than those with genotype AB. These results preliminarily indicated that the KiSS-1 gene may have some association with prolificacy in sheep.

The bone morphogenetic protein receptor IB (BMPR-IB) was studied as a candidate gene for the prolificacy of sheep. Nine pairs of primers (P1-P9) were designed to detect single nucleotide polymorphisms (SNPs) of exons 1-4 and 6-10 of the BMPR-IB gene in both high (Small Tail Han and Hu sheep) and low prolificacy breeds (Texel and Chinese Merino sheep) by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP). Only the products amplified by primers P2, P5, P6, P7, P8 and P9 displayed polymorphisms. The present study identified 22 SNPs in partial coding regions of ovine BMPR-IB, in which 20 SNPs were reported for the first time. In total of the 22 mutations, 18 DNA variations were originated from the Hu breed, three were found in the Small Tail Han breed (two of them were found in other sheep breeds), three in the Chinese Merino breed, and none in the Texel breed. These results preliminarily demonstrated that BMPR-IB is a major gene affecting the hyperprolificacy in Small Tail Han and Hu sheep, and could be used as a molecular genetic marker for early auxiliary selection for hyperprolificacy in sheep.

This study assessed the usefulness of geographic and pairwise genetic distances in the characterization of five sheep populations using 15 microsatellite markers. The average F statistics across loci were F (IT) = 0.523 +/- 0.140, F (ST) = 0.363 +/- 0.131, and F (IS) = 0.263 +/- 0.092. The average heterozygosity was 0.716 +/- 0.069, polymorphism information content was 0.691 +/- 0.070, and effective number of alleles was 3.736 +/- 0.998. Sheep populations clustered into group 1 (Hu and Tong breeds) and group 2 (small-tailed Han, Wadi, and Tan breeds). Reynolds' distance varied from 0.0062 to 0.0499, and the range of gene flow (N (m)) was 4.8834-40.0726 among the sheep populations. The results showed that the genetic structure of the five populations was not consistent with their genetic distances, and the population genetic divergence was not linearly related to geographic distance as indicated by a Mantel test (P = 0.7936).

Simple Summary: We performed a genome-wide association study of 100 sheep genomes to investigate the hereditary basis of the four-horn phenotype (FHP) in sheep. The results revealed that a total of 3 InDels (e.g., CHR2: g.133,742,709delA and g.133,743,215insC) and 14 SNPs (e.g., CHR2: g.133,727,513C > T and CHR16: g.40,351,378G > A) in CHR2 and CHR16 were significantly associated with the four-horn trait. Furthermore, HOXD1 and ADAMTS12 annotated from both CHR sequences were the key candidate gene loci contributing to FHP in sheep. This study provided a novel understanding of the Mendelian genetic basis for four horns in sheep. Horns are an important breeding trait for sheep. However, no widely recognized viewpoint on the regulatory genes and mechanisms of horns is available, and the genetic basis of the four-horn phenotype (FHP) is unclear. This work conducted a genome-wide association study with 100 sheep genomes from multiple breeds to investigate the genetic basis of the FHP. The results revealed three significant associations (corrected as p < 1.64 × 10−8) of the InDels (CHR2: g.133,742,709delA, g.133,743,215insC, and g.133,743,940delT) for FHP in the intergenic sequence (IGS) between the MTX2 and the LOC105609047 of CHR2. Moreover, 14 significant associations (corrected as p < 1.42 × 10−9) of SNPs with the FHP phenotype were identified in CHR2 and CHR16, including five (e.g., CHR16: g.40,351,378G > A and g.40,352,577G > A) located in the intron of the ADAMTS12 gene, eight (e.g., CHR2: g.133,727,513C > T and g.133,732,145T > G) in the IGS between MTX2 and LOC105609047, and only one (CHR2: g.133,930,761A > G) in the IGS between HOXD1 and MTX2. Obvious divergence was also observed in genotype patterns between the FHP and others (two horns and hornless) in the HOXD1 and ADAMTS12 gene regions. An extremely significant linkage also occurred between Loci I and Loci II within 100 individuals (LD = −156.02186, p < 0.00001). In summary, our study indicated that the genomic sequences from CHR2 and CHR16 contributed to the FHP in sheep, specifically the key candidate genes HOXD1 and ADAMTS12. These results improved our understanding of the Mendelian genetic basis of the FHP in sheep. [ABSTRACT FROM AUTHOR]

Tibetan sheep are one of the three major coarse sheep breeds in China, and they possess a long history of formation. However, few studies have been conducted on the identification of Tibetan sheep breeds at the molecular level. In this study, a total of 448 individuals from 24 Tibetan sheep populations in the 5 regions of Tibet, Qinghai, Gansu, Yunnan, and Sichuan were analyzed using the Affymetrix Ovine SNP 600K high-density chip to construct specific single-nucleoside polymorphism (SNP) genetic marker sets of Tibetan sheep breeds. Firstly, the genetic structure analysis showed that Yunnan–Tibetan sheep (NL, Ninglang; JC, Jianchuan), Zuogong (ZG), Heizang (HZ), Gongga (GG,) and Tao sheep (TS) can be clearly distinguished from other Tibetan sheep populations. Next, based on the population differentiation index FST, the PCA and NJ tree results showed that only 60 specific SNPs can successfully separate Tibetan sheep in the Yunnan region from Tibetan sheep in other regions, and the distinguishing effect on Yunnan–Tibetan sheep reached 100%. Using the same method, we found that 4 Tibetan sheep breeds, including Zuogong (ZG, 20 SNPs), Heizang (HZ, 60 SNPs), Gongga (GG, 60 SNPs), and Tao sheep (TS, 30 SNPs), can also be distinguished from other Tibetan sheep populations with only a few SNP loci (20–60), and the distinguishing effect reached 100%. Overall, we successfully obtained a Yunnan region-specific (60 SNPs) genetic marker set and 4 breed-specific SNP genetic marker sets (20–60 SNPs) for the first time for the identification of Tibetan sheep breeds at the molecular level. These made up for the lack of genetic marker sets for the identification of Tibetan sheep breeds, and provided a genomic basis for the scientific classification and accurate identification of livestock and poultry genetic resources on the Qinghai–Tibet Plateau. [ABSTRACT FROM AUTHOR]

As relatively new members of the non-coding RNA family, circRNAs play important roles in a variety of biological processes. However, the temporal expression pattern and the function of circRNAs during sheep skeletal muscle development remains unclear. This study aimed to identify circRNAs related to sheep skeletal muscle development and explore their roles in myoblast proliferation. The circRNA expression profiles of longissimus dorsi of sheep from F90, L30, and A3Y were obtained by the RNA-seq method. The function and mechanisms of the novel circCHRNG in muscle satellite cell proliferation were explored using CCK-8 assay, Western blot, qPCR, and dual-luciferase reporter assay. We identified 12,375 circRNAs, including 476, 133, and 233 DEcircRNAs found among three comparative groups. KEGG results showed that DEcircRNAs were enriched in muscle contraction, the regulation of cell proliferation, and the AMPK, insulin, and PI3K-Akt signaling pathways. Notably, a novel circRNA, termed circRNA CHRNG, acts as a miR-133 sponge to promote skeletal muscle satellite cell proliferation. Our study provides a systematic description of circRNAs of ovine skeletal muscle across fetal, lamb, and adult stages. GO and KEGG analyses showed that DEcircRNAs were enriched in multiple pathways associated with muscle development, such as the PI3K-Akt and AMPK signaling pathways. In addition, we propose that circCHRNG acts as a miR-133 sponge to upregulate the expression levels of SRF and MEF2A, thereby promoting myoblast proliferation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the family structure, parent–child pair and inbreeding coefficient of a Tan sheep breeding farm in Ningxia, China. The results can be used as the theoretical basis for selecting excellent breeding stock and making an apposite mating plan; furthermore, it can provide an important scientific basis for the conservation and reproduction of Tan sheep germplasm resources. Tan sheep is a special breed of locally protected sheep in China, one of the best quality meat sheep in the world. Due to the unclear pedigree of the rams on the Ningxia Tan sheep breeding farm, we investigated 74 rams in the field and explored a new method for family division. Genomic DNA was extracted from the blood of breeding rams. Using Plink software, GCTA tools and R language, we analyzed the genetic structure, kinship, and inbreeding coefficient of the breeding sheep, which revealed the genetic relationship between the individuals. The results showed that there was no obvious clustering phenomenon in the PCA, and the genetic background of the samples was similar. The G matrix and IBS distance matrix indicated that most individuals were far away from each other. Paternity testing identified 24 pairs of unknown parent–child pairs, and all the Tan sheep could be divided into 12 families, which provided a reference for sheep breeding. The average inbreeding coefficient based on the ROH of this population was 0.049, so there was a low degree of inbreeding and the rams in the field were able to maintain high genetic diversity. Overall, we explored a more accurate method through paternity and kinship analysis; it provides a scientific basis for pedigree construction, which has an important application value for Tan sheep breeding. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

With climate change bound to affect food and feed production, emphasis will shift to resilient and adapted indigenous livestock to sustain animal production. However, indigenous livestock comprise several varieties, strains and ecotypes whose genomes are poorly characterized. Here, we investigated genomic variation in an African thin-tailed Desert Sheep sampled in Sudan, using 600K genotype data generated from 92 individuals representing five ecotypes. We included data from 18 fat-tailed and 45 thin-tailed sheep from China, to investigate shared ancestry and perform comparative genomic analysis. We observed a clear genomic differentiation between the African thin-tailed Desert Sheep and the Chinese thin-tailed and fat-tailed sheep, suggesting a broad genetic structure between the fat-tailed and thin-tailed sheep in general, and that at least two autosomal gene pools comprise the genome profile of the thin-tailed sheep. Further analysis detected two distinct genetic clusters in both the African thin-tailed Desert Sheep and the Chinese thin-tailed sheep, suggesting a fine-scale and complex genome architecture in thin-tailed sheep. Selection signature analysis suggested differences in adaptation, production, reproduction and morphology likely underly the fine-scale genetic structure in the African thin-tailed Desert Sheep. This may need to be considered in designing breeding programs and genome-wide association studies. [ABSTRACT FROM AUTHOR]

The hair follicle is a complex mini-organ in the skin that undergoes organ induction, morphogenesis, and regeneration. However, the accurate molecular mechanism of skin and hair diversity regulation is still elusive. The sheep is an animal model that can be used to further explore the mechanisms of skin and hair diversity. In this study, we carried out a transcriptomic analysis of the mRNA expression in the skin of Xinji fine-wool sheep at different growth stages (3 and 12 months old) and 12-month-old Tan sheep and explored the transcripts' relationship with hair follicle growth. A total of 1327 mRNAs and 67 transcription factors were identified to be differentially expressed in the different breeds and during different periods of skin development. The differentially expressed genes were enriched in GO terms represented by system development, multicellular organism development, animal organ development, and skin development, and three KEGG pathways typified those governing differences in skin structure. Combining protein–protein interaction networks of skin development (GO:0043588) and functional annotation, nine important candidate genes, namely, LAMA5, OVOL1, SRF, DHCR24, NGFR, SMO, CDSN, HOXC13, and KDF1, and many core genes with minor effects were confirmed to be associated with hair follicle development. Furthermore, members of the zf-C2H2 and homeobox transcription factor families, which were identified to play a crucial role in producing finer and denser wool, were mainly upregulated in 12-month-old Xinji fine-wool sheep when compared with expression in 12-month-old Tan sheep and 3-month-old Xinji fine-wool sheep. This study revealed the major–minor gene interactions in the developmental pathway and provided ideas for an in-depth understanding of the genetic structure and gene regulation in the skin/hair growth process. [ABSTRACT FROM AUTHOR]

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 (ΔDAF). 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Sheep is one of the most economically important animals used as a source of meat, milk, wool, and fur for human society. These commodities are essential for human being. Body growth, body weight, carcass quality, fat percent, fertility, milk yield, wool, horn type and coat color are essential and useful sheep traits. Understanding the genetic background of these traits is paramount to increase the production and productivity of domestic animals. The availability of genomic data, development of molecular breeding techniques, and genome technologies have come to play a vital role in understanding the genetic background of different animal traits. This is directly or indirectly helpful for the practice of genetic improvement of economically important traits in sheep. The identification of genomic regions, genes associated with phenotypic traits, and description of gene function are some of the applied research activities to understand the genetics of livestock species. The aim of this review is to discuss and summarize different reported research findings on identified genomic regions and candidate genes related with economically important traits as well as gene annotation in sheep. Sheep (Ovis aries) is one of the most economically, culturally, and socially important domestic animals. They are reared primarily for meat, milk, wool, and fur production. Sheep were reared using natural selection for a long period of time to offer these traits. In fact, this production system has been slowing the productivity and production potential of the sheep. To improve production efficiency and productivity of this animal through genetic improvement technologies, understanding the genetic background of traits such as body growth, weight, carcass quality, fat percent, fertility, milk yield, wool quality, horn type, and coat color is essential. With the development and utilization of animal genotyping technologies and gene identification methods, many functional genes and genetic variants associated with economically important phenotypic traits have been identified and annotated. This is useful and presented an opportunity to increase the pace of animal genetic gain. Quantitative trait loci and genome wide association study have been playing an important role in identifying candidate genes and animal characterization. This review provides comprehensive information on the identified genomic regions and candidate genes associated with production and reproduction traits, and gene function in sheep. [ABSTRACT FROM AUTHOR]

[Display omitted] • We find two functional mutations driving the finer and denser wool production. • One C/A missense variant of KRT74 drive finer wool production in Chinese fine wool sheep. • The C-KRT74 can activate the KRT74 protein and affect wool fineness. • One T/C SNP in the regulatory region upstream of EDAR drive denser wool production in fine wool sheep. • The C-to-T mutation can upregulate EDAR mRNA expression and potentially affect wool density. 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. This study aims to clarify the underlying genetic basis for the denser and finer wool phenotype in fine-wool breeds. 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. 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. 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. [ABSTRACT FROM AUTHOR]