A repertoire of single nucleotide polymorphisms (SNPs) of major fecundity BMPR1B gene among 75 sheep breeds worldwide.

The BMPR1B gene is a major determinant of sheep reproductive capacity. Previous studies revealed that Q249R (FecB) is a profound variant of BMPR1B that influences the ovulation rate and litter size in sheep. However, unlike Q249R locus, the full spectrum of single nucleotide polymorphisms (SNPs) within BMPR1B has not been extensively studied. A systematic screen of SNPs in BMPR1B would facilitate the discovery of novel variants that are associated with litter size. This study aimed to investigate SNPs in the BMPR1B gene via whole genome sequence (WGS) data from 2409 individuals of 75 sheep breeds worldwide. Herein, a total of 9688 variants were screened, among which 15 were coding variants and 8 were novel changes. Specifically, we presented the most comprehensive frequency distribution map of the well-known FecB mutation to date. Besides, among the above-mentioned SNPs, one synonymous mutation (g.30050773C > T) was found to be likely under selection and is potentially associated with fecundity in Duolang sheep. Thus, our study greatly expands the variation repertoire of the ovine BMPR1B gene and provides a valuable resource for exploring causative mutations and genetic markers associated with litter size.

Whole-genome resequencing reveals the genomic diversity and signatures of selection in Romanov sheep.

Romanov sheep are adapted to the extremely cold and harsh environment and display a distinctive grey color. Herein, we analyzed the population structure, genetic diversity, and selection signatures of Romanov sheep based on whole-genome sequencing data of 17 Romanov sheep, 114 individuals from other 10 European breeds. The results of PCA, ADMIXTURE, and NJ-tree showed that the Romanov sheep was closely related to other northern European breeds. A relative high level of genetic diversity, low inbreeding coefficient, and large effective population size was observed in Romanov sheep when compared with other European breeds. We then screened the genomic selection signatures of Romanov sheep using FST, XP-XLP, and XP-EHH methods. The most significant region under selection (CHR14:14.2 to 14.3 Mb) harbored a haplotype that contained MC1R gene. Furthermore, this haplotype was also found in other grey-body breeds including Gotland sheep, Grey Tronder Sheep, and German grey heath sheep, suggesting that it was associated with the unique coat color of these breeds. We also found one region (CHR10:40.8Mb- 41.0Mb) harboring PCDH9 gene which was potentially associated with cold environmental adaptation. In summary, this study identified candidate genes that were associated with the unique grey color and environmental adaptation in Romanov sheep, which provided a basis for understanding the genetic background and utilization of this breed.

Romanov sheep is one of the most famous sheep breeds in the word, characterized by adaptability to harsh environment, high fertility, and unique coat color. Understanding its genetic architecture and signatures is of great value for its conservation and utilization. In this study, we analyzed whole-genome sequences of Romanov sheep as compared with 11 other European breeds, to explore for the population structure, genetic diversity, and selection signatures. We discovered a series of candidate genes that likely play a role in the grey coat color and cold adaptation of the Romanov sheep. In particular, we identified MC1R as a strong candidate gene that determines the grey coat color.

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes.

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

Convergent changes in melanocortin receptor 1 gene are associated with black-headed coat color in sheep.

As one of the most obvious phenotypic traits, the coat color of sheep is an ideal model to study the genetic mechanisms underlying coat color varieties of mammals. One distinguishable coat color is the black-headed type, such as the famous black-headed Dorper sheep from Africa and Bayinbuluke sheep from Asia. In this study, we compared the genome sequences of black-headed and all-white sheep to identify causative genes for the black-headed sheep, including black-headed Dorper vs. white-headed Dorper, as well as Bayinbuluke (black-headed) vs. Small-tailed Han (all-white). The most differentiating region between black-headed sheep and all-white sheep was found to harbor a haplotype covering melanocortin receptor 1 (MC1R) gene. The share of this haplotype by the black-headed sheep from Africa and Asia suggested that the convergent change in the MC1R region is likely to determine this unique coat color. Two missense mutations (g. 14251947T > A and g. 14252090G > A) within this haplotype of MC1R gene were found. We further analyzed whole genome sequence data of 460 worldwide sheep with diverse coat colors and confirmed the association between the MC1R haplotype with pigmentation variations. Our study provides novel insights into coat color genetics in sheep and expands our knowledge of the link between MC1R gene and varying pigmentation patterns in sheep.

The diverse colors of sheep not only help to distinguish different breeds but also provide an ideal model to study the genetics underlying mammalian coat color variations. One unique coat color in sheep is the black-headed type, as represented by the famous meat breed Dorper sheep from Africa and Bayinbuluke sheep from Asia. In this study, we compared the genomes of black-headed sheep with all-white sheep in order to identify genes responsible for this distinguishable coat color. By analyzing genomic selection signals and haplotypes, we located MC1R as the most likely causative gene determining the black-headed coat color in sheep. Our study expanded our understanding of the genetic mechanisms of coat color diversities in sheep.

Newly reported 90-bp deletion within the ovine BMPRIB gene: Does it widely distribute, link to the famous FecB (p.Q249R) mutation, and affect litter size?

The study of the BMPRIB gene polymorphisms has become of great importance in sheep, because it provides critical genetic tools to improve reproductive efficiency in ewes. The purposes of this study were: to assess the genetic diversity of the 90-bp deletion polymorphism within the BMPRIB gene in 52 various sheep breeds; to examine its linkage to the p.Q249R variant in the same gene, as well as to analyze its association with litter size. Herein, a total of 2313 various sheep individuals were used to detect the presence of the 90-bp deletion, among them the six breeds (Australian White (AUW), Small-Tail Han (STH), Guiqian semi-fine wool (GQSFW) sheep, etc.) were genotyped using PCR-based genotyping technology (n = 1636), and 47 breeds worldwide (including STH sheep) were genotyped via whole genome sequencing (WGS) method (n = 677). Genotyping outcomes revealed that the polymorphism was segregated in 45 of 52 breeds with varying frequencies (0.05-0.93). It is pertinent to note that the 90-bp deletion is not linked to the famous p.Q249R SNP in population of interest, except in high prolific Hu sheep. The association analysis indicated that the Del-90-bp variant showed no significant association (P > 0.05) with litter size in AUW (n = 625), GQSFW (n = 75) and STH (n = 38) ewes. Nevertheless, further investigation is needed on the importance of the Del-90-bp variant as a DNA marker that could possibly serve as an additional selection criterion in breeding ewes with high productivity.

A Hu sheep genome with the first ovine Y chromosome reveal introgression history after sheep domestication.

The Y chromosome plays key roles in male fertility and reflects the evolutionary history of paternal lineages. Here, we present a de novo genome assembly of the Hu sheep with the first draft assembly of ovine Y chromosome (oMSY), using nanopore sequencing and Hi-C technologies. The oMSY that we generated spans 10.6 Mb from which 775 Y-SNPs were identified by applying a large panel of whole genome sequences from worldwide sheep and wild Iranian mouflons. Three major paternal lineages (HY1a, HY1b and HY2) were defined across domestic sheep, of which HY2 was newly detected. Surprisingly, HY2 forms a monophyletic clade with the Iranian mouflons and is highly divergent from both HY1a and HY1b. Demographic analysis of Y chromosomes, mitochondrial and nuclear genomes confirmed that HY2 and the maternal counterpart of lineage C represented a distinct wild mouflon population in Iran that diverge from the direct ancestor of domestic sheep, the wild mouflons in Southeastern Anatolia. Our results suggest that wild Iranian mouflons had introgressed into domestic sheep and thereby introduced this Iranian mouflon specific lineage carrying HY2 to both East Asian and Africa sheep populations.

Single nucleotide polymorphisms of myostatin gene in Chinese domestic horses.

The myostatin gene (MSTN) is a genetic determinant of skeletal muscle growth. Single nucleotide polymorphisms (SNP) in MSTN are of importance due to their strong associations with horse racing performances. In this study, we screened the SNPs in MSTN gene in 514 horses from 15 Chinese horse breeds. Six SNPs (g.26T>C, g.156T>C, g.587A>G, g.598C>T, g.1485C>T, g.2115A>G) in MSTN gene were detected by sequencing and genotyped using PCR-RFLP method. The g.587A>G and g.598C>T residing in the 5'UTR region were novel SNPs identified by this study. The g.2115A>G which have previously been associated with racing performances were present in Chinese horse breeds, providing valuable genetic information for evaluating the potential racing performances in Chinese domestic breeds. The six SNPs together defined thirteen haplotypes, demonstrating abundant haplotype diversities in Chinese horses. Most of the haplotypes were shared among different breeds with no haplotype restricted to a specific region or a single horse breed. AMOVA analysis indicated that most of the genetic variance was attributable to differences among individuals without any significant contribution by the four geographical groups. This study will provide fundamental and instrumental genetic information for evaluating the potential racing performances of Chinese horse breeds.