Runs of Homozygosity Detection and Selection Signature Analysis for Local Goat Breeds in Yunnan, China.

Runs of Homozygosity (ROH) are continuous homozygous DNA segments in diploid genomes, which have been used to estimate the genetic diversity, inbreeding levels, and genes associated with specific traits in livestock. In this study, we analyzed the resequencing data from 10 local goat breeds in Yunnan province of China and five additional goat populations obtained from a public database. The ROH analysis revealed 21,029 ROH segments across the 15 populations, with an average length of 1.27 Mb, a pattern of ROH, and the assessment of the inbreeding coefficient indicating genetic diversity and varying levels of inbreeding. iHS (integrated haplotype score) was used to analyze high-frequency Single-Nucleotide Polymorphisms (SNPs) in ROH regions, specific genes related to economic traits such as coat color and weight variation. These candidate genes include OCA2 (OCA2 melanosomal transmembrane protein) and MLPH (melanophilin) associated with coat color, EPHA6 (EPH receptor A6) involved in litter size, CDKAL1 (CDK5 regulatory subunit associated protein 1 like 1) and POMC (proopiomelanocortin) linked to weight variation and some putative genes associated with high-altitude adaptability and immune. This study uncovers genetic diversity and inbreeding levels within local goat breeds in Yunnan province, China. The identification of specific genes associated with economic traits and adaptability provides actionable insights for utilization and conservation efforts.

Correction: Luan et al. Identification of Critical Genes for Ovine Horn Development Based on Transcriptome during the Embryonic Period. Biology 2023, 12, 591.

In the original publication [1], there were mistakes in the order of the references, which were as follows: [...].

Identification of Critical Genes for Ovine Horn Development Based on Transcriptome during the Embryonic Period.

Horns, also known as headgear, are a unique structure of ruminants. As ruminants are globally distributed, the study of horn formation is critical not only for increasing our understanding of natural and sexual selection but also for the breeding of polled sheep breeds to facilitate modern sheep farming. Despite this, a significant number of the underlying genetic pathways in sheep horn remain unclear. In this study, to clarify the gene expression profile of horn buds and investigate the key genes in horn bud formation, RNA-sequencing (RNA-seq) technology was utilized to investigate differential gene expression in the horn buds and adjacent forehead skin of Altay sheep fetuses. There were only 68 differentially expressed genes (DEGs) identified, consisting of 58 up-regulated genes and 10 down-regulated genes. RXFP2 was differentially up-regulated in the horn buds and had the highest significance (p-value = 7.42 × 10-14). In addition, 32 DEGs were horn-related genes identified in previous studies, such as RXFP2, FOXL2, SFRP4, SFRP2, KRT1, KRT10, WNT7B, and WNT3. Further, Gene Ontology (GO) analysis showed that the DEGs were mainly enriched with regard to growth, development, and cell differentiation. Pathway analysis revealed that the Wnt signaling pathway may be responsible for horn development. Further, through combining the protein-protein interaction networks of the DEGs, it was found that the top five hub genes, namely, ACAN, SFRP2, SFRP4, WNT3, and WNT7B, were also associated with horn development. Our results suggest that only a few key genes, including RXFP2, are involved in bud formation. This study not only validates the expression of candidate genes identified at the transcriptome level in previous studies but also provides new possible marker genes for horn development, which may promote our understanding of the genetic mechanisms of horn formation.

Transcriptomic Analysis Reveals mRNA and Alternative Splicing Events in Ovine Skeletal Muscle Satellite Cells during Proliferation and Differentiation.

Skeletal muscle satellite cells (SMSCs), which are highly multifunctional muscle-derived stem cells, play an essential role in myogenesis and regeneration. Here, the transcriptional profile of SMSCs during proliferation and differentiation were constructed using the RNA-Seq method. A total of 1954 differentially expressed genes (DEGs) and 1092 differentially alternative splicing genes (DAGs) were identified including 1288 upregulated genes as well as 666 downregulated genes. GO and KEGG analyses showed that the DEGs and DAGs were enriched in the MAPK (mitogen-activated protein kinase) signaling pathway, the PI3K-Akt (phosphatidylinositol-tris-phosphate kinase 3/protein kinase B) signaling pathway, the Wnt signaling pathway, and the Ras signaling pathway. In total, 1479 alternative splice events (AS) were also identified during SMSC proliferation and differentiation. Among them, a unique AS event was the major per-mRNA splicing type, and SE was the predominant splicing pattern. Furthermore, transcription factors with AS were scanned during SMSC differentiation such as myocyte enhancer factor-2C (MEF2C) and the nuclear receptor subfamily 4 group A member 2 (NR4A2). Our results imply that MEF2C and NR4A2 can interact, and we speculate that NR4A2 and MEF2C might regulate the myogenesis of ovine SMSCs through interaction. Together, our study provides useful information on the transcriptional regulation of SMSCs during proliferation and differentiation at the transcriptional level, and provides a valuable resource for understanding the molecular mechanism of myogenesis and muscle development.

A genome-wide perspective on the diversity and selection signatures in indigenous goats using 53 K single nucleotide polymorphism array.

Tibetan goats, Taihang goats, Jining grey goats, and Meigu goats are the representative indigenous goats in China, found in Qinghai-Tibet Plateau, Western pastoral area, Northern and Southern agricultural regions. Very few studies have conducted a comprehensive analysis of the genomic diversity and selection of these breeds. We genotyped 96 unrelated individuals, using goat 53 K Illumina BeadChip array, of the following goat breeds: Tibetan (TG), Taihang (THG), Jining grey (JGG), and Meigu (MGG). A total of 45 951 single nucleotide polymorphisms were filtered to estimate the genetic diversity and selection signatures. All breeds had a high proportion (over 95%) of polymorphic loci. The observed and excepted heterozygosity ranged from 0.338 (MGG) to 0.402 (JGG) and 0.339 (MGG) to 0.395 (JGG), respectively. Clustering analysis displayed a genetically distinct lineage for each breed, and their Fst were greater than 0.25, indicating that they had a higher genetic differentiation between groups. Furthermore, effective population size reduced in all four populations, indicating a loss of genetic diversity. In addition, runs of homozygosity were mainly distributed in 5-10 Mb. Lastly, we identified signature genes, which were closely related to high-altitude adaptation (ADIRF) and prolificity (CNTROB, SMC3, and PTEN). This study provides a valuable resource for future studies on genome-wide perspectives on the diversity and selection signatures of Chinese indigenous goats.

Genome-Wide Analysis of Circular RNAs Reveals circCHRNG Regulates Sheep Myoblast Proliferation via miR-133/SRF and MEF2A Axis.

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.

Early Weaning and Milk Substitutes Affect the Gut Microbiome, Metabolomics, and Antibody Profile in Goat Kids Suffering From Diarrhea.

Early weaning and milk substitutes increase the incidence of diarrhea in young ruminants, which may modify their gut microbiota, metabolism, immunity, and health. The aim of the study was to determine if early weaning and milk substitutes affect the gut microbiota, metabolism, and immunological status of goat kids suffering from diarrhea. The 16S rRNA gene and metagenomic sequencing in feces and serum metabolomics of early-weaned and artificially reared goat kids suffering from diarrhea (DK group) and healthy goat kids reared by their mothers (HK group) were analyzed. The serum biochemistry and immunoglobulin concentration were also determined. Several probiotics, such as Streptococcus and Lactobacillus, were higher in the feces of the DK group than in feces of the HK group. Ruminococcus sp. was elevated in the feces of HKs, likely being a biomarker for goat health. Taking all the carbohydrate-active enzyme (CAZyme) families into consideration, 20 CAZyme families were different between the groups. Compared with the DK group, the relative quantity of glycoside hydrolases (GH) and glycosyltransferase (GT) families in the HK group decreased. GT70 was only identified in HK kids participating in the activity of ß-glucuronosyltransferase during the carbohydrate metabolism. Overall, 24 metabolites were different between the groups, which were mainly involved in protein digestion and absorption, cyanoamino acid metabolism, and cholesterol metabolism. The concentrations of immunoglobulins G and M were significantly lower in the DK than in the HK group. In conclusion, our study characterized the fecal microbiota, metabolism, and immunological status of early-weaned and artificially reared goat kids suffering from diarrhea.

Integration Analysis of Transcriptome and Proteome Reveal the Mechanisms of Goat Wool Bending.

Zhongwei goat is a unique Chinese native goat breed for excellent lamb fur. The pattern of flower spikes of the lamb fur was significantly reduced due to the reduction of the bending of the hair strands with growth. In order to explore the molecular mechanism underlying hair bending with growth, we performed the comprehensive analysis of transcriptome and proteome of skins from 45-days, 108-days and 365-days goat based on TMT-based quantitative proteomics and RNA-seq methods. In the three comparison groups, 356, 592 and 282 differentially expressed proteins (DEPs) were screened, respectively. KEGG pathway analysis indicated that DEPs were significantly enriched in a set of signaling pathways related to wool growth and bending, such as ECM-receptor interaction, PI3K-Akt signaling pathway, PPAR signaling pathway, protein digestion and absorption, and metabolic pathways. In addition, 20 DEPs abundance of goat skin at three development stages were examined by PRM method, which validated the reliability of proteomic data. Among them, KRT and collagen alpha family may play an important role in the development of goat hair follicle and wool bending. COL6A1, COL6A2, CRNN, TNC and LOC102178129 were identified as candidate genes based on combined analysis of transcriptome and proteome data and PRM quantification. Our results identify the differential expressed proteins as well as pathways related to the wool bending of Zhongwei goats and provide a theoretical basis for further revealing the molecular mechanism underlying wool bending of goats.

Integrated Analysis of lncRNA and mRNA Reveals Novel Insights into Wool Bending in Zhongwei Goat.

Chinese Zhongwei goat is a rare and precious fur breed as its lamb fur is a well-known fur product. Wool bending of lamb fur of the Zhongwei goat is its most striking feature. However, the curvature of the wool decreases gradually with growth, which significantly affects its quality and economic value. The mechanism regulating the phenotypic changes of hair bending is still unclear. In the present study, the skin tissues of Zhongwei goats at 45 days (curving wool) and 108 days (slight-curving wool) after birth were taken as the research objects, and the expression profiling of long non-coding RNAs (lncRNAs) and mRNAs were analyzed based on the Ribo Zero RNA sequencing (RNA-seq) method. In total, 46,013 mRNAs and 13,549 lncRNAs were identified, of which 352 were differentially expressed mRNAs and 60 were. lncRNAs. Functional enrichment analysis of the target genes of lncRNAs were mainly enriched in PI3K-Akt, Arachidonic acid metabolic, cAMP, Wnt, and other signaling pathways. The qRT-PCR results of eight selected lncRNAs and target genes were consistent with the sequencing result, which indicated our data were reliable. Through the analysis of the weighted gene co-expression network, 13 co-expression modules were identified. The turquoise module contained a large number of differential expressed lncRNAs, which were mainly enriched in the PI3K-Akt signaling pathway and cAMP signaling pathway. The predicted LOC102172600 and LOC102191729 might affect the development of hair follicles and the curvature of wool by regulating the target genes. Our study provides novel insights into the potential roles of lncRNAs in the regulation of wool bending. In addition, the study offers a theoretical basis for further study of goat wool growth, so as to be a guidance and reference for breeding and improvement in the future.

Genome Divergence and Dynamics in the Thin-Tailed Desert Sheep From Sudan.

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.

Genome-wide comparative analyses reveal selection signatures underlying adaptation and production in Tibetan and Poll Dorset sheep.

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 FST, 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.

Genome-Wide Analysis Revealed Homozygosity and Demographic History of Five Chinese Sheep Breeds Adapted to Different Environments.

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.

Expression Profiling and Functional Characterization of miR-26a and miR-130a in Regulating Zhongwei Goat Hair Development via the TGF-ß/SMAD Pathway.

The Zhongwei goat is an important and unique goat breed indigenous to China. It has a natural hair curling phenotype at birth, but the degree of curling gradually decreases with growth. The molecular mechanism underlying the dynamic changes in the wool curvature in Zhongwei goats is poorly understood. MicroRNAs (miRNAs) play important roles in many biological processes, including hair growth and development. In this study, we selected skins from Zhongwei goats at different ages (45 and 108 days) that exhibited different levels of hair curvature and performed miRNA sequencing to explore the molecular mechanism of hair bending. In total, 28 significantly differentially expressed miRNAs (DE miRNAs) were identified in the three groups of samples between the two developmental stages. An analysis of the target genes of the above-mentioned DE miRNAs by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the DE miRNAs were involved in signal pathways which were previously associated with hair bending and hair follicle development, such as the TGF-ß/SMAD, PI3K-Akt, JAK-STAT, and MAPK pathways. A comprehensive analysis of the correlations between the miRNA-seq results and issued transcriptional findings indicated that SMAD1 was a target gene of miR-26a and SMAD5 was a target gene of miR-130a. Furthermore, goat dermal papilla cells were successfully isolated and purified to determine the role of miRNAs in follicle development in vitro. The study results demonstrated that miR-130a and miR-26a had significant effects on the proliferation of dermal papilla cells. In addition, the detection results of mRNA and protein levels indicate that the overexpression of miR-26a can promote the expression of related genes in the TGF-ß/SMAD pathway, while miR-130a has the opposite substitution effect. The dual luciferase report test showed that miR-26a targeted the SMAD1 gene and reduced the expression of the SMAD1 protein in hair papillary cells. Our results identified DE microRNAs which perhaps change at the time of hair straightening in Zhongwei goats and explore the role of miR-26a and miR-130a in dermal papilla cells proliferation. The present study provided a theoretical basis to explore the mechanisms underlying the Zhongwei hair growth and curly phenotype.

Genomic Diversity, Population Structure, and Signature of Selection in Five Chinese Native Sheep Breeds Adapted to Extreme Environments.

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 (FST) 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 FST 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.

Local origin or external input: modern horse origin in East Asia.

BACKGROUND: Despite decades of research, the horse domestication scenario in East Asia remains poorly understood. RESULTS: The study identified 16 haplogroups with fine-scale phylogenetic resolution using mitochondrial genomes of 317 horse samples. The time to the most recent common ancestor of the 16 haplogroups ranges from [0.8-3.1] thousand years ago (KYA) to [7.9-27.1] KYA. With combined analyses of the mitochondrial control region for 35 extant Przewalski's horses, 3544 modern and 203 ancient horses across the world, researchers provide evidence for that East Asian prevalent haplogroups Q and R were indigenously domesticated or they were involved in numerous distinct genetic components from wild horses in the southern part of East Asia. These events of haplotypes Q and R occurred during 4.7 to 16.3 KYA and 2.1 to 11.5 KYA, respectively. The diffusion of preponderant European haplogroups L from west to East Asia is consistent with the external gene input. Furthermore, genetic differences were detected between northern East Asia and southern East Asia cohorts by Principal Component Analysis, Analysis of Molecular Variance test, the χ2 test and phylogeographic analyses. CONCLUSIONS: All results suggest a complex picture of horse domestication, as well as geographic pattern in East Asia. Both local origin and external input occurred in East Asia horse populations. And besides, there are at least two different domestication or hybridization centers in East Asia.

EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses.

High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski's horses added for comparison. We find that Tibetan horses do not descend from Przewalski's horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

Insights into the genetic diversity of indigenous goats and their conservation priorities.

Objective: An experiment was conducted to evaluate genetic diversity of 26 Chinese indigenous goats by 30 microsatellite markers, and then to define conservation priorities to set up the protection programs according to the weight given to within- and between-breed genetic diversity. Methods: Twenty-six representative populations of Chinese indigenous goats, 1351 total, were sampled from different geographic regions of China. Within-breed genetic diversity and marker polymorphism were estimated calculating the mean number of alleles (MNA), observed heterozygosities (HO), expected heterozygosities (He), fixation index (FIS), effective number of alleles (NE) and allelic richness (Rt). Conservation priorities were analyzed by statistical methods. Results: A relatively high level of genetic diversity was found in twenty-four populations, the exceptions were in the Daiyun and Fuqing goat populations. Within-breed kinship coefficients matrix identified seven highly inbred breeds which should be concerned. Of these, six breeds will get a negative contribution to heterozygosity when the method was based on proportional contribution to heterozygosity. Based on Weitzman or Piyasatian and Kinghorn methods, the breeds distant from others i.e. Inner Mongolia Cashmere goat, Chengdu Brown goat and Leizhou goat will obtain a high ranking. Evidence from Caballero and Toro and Fabuel et al. method prioritized Jining Gray goat, Liaoning Cashmere goat and Inner Mongolia Cashmere goat, that in agreement with results from Kinship-based methods. Conclusion: Conservation priorities had planned according to multiple methods. Our results suggest Inner Mongolia Cashmere goat (most methods), Jining Gray goat and Liaoning Cashmere goat (high contribution to heterozygosity and total diversity) should be prioritized based on most methods. Furthermore, Daiyun goat and Shannan White goat also should be prioritized based on consideration of effective population size. However, if one breed could survive in changing conditions all the time, the straightforward approach is to increase its utilization and attraction for production via mining breed germplasm characteristic.

Integrated Analysis of Methylome and Transcriptome Changes Reveals the Underlying Regulatory Signatures Driving Curly Wool Transformation in Chinese Zhongwei Goats.

The Zhongwei goat is kept primarily for its beautiful white, curly pelt that appears when the kid is approximately 1 month old; however, this representative phenotype often changes to a less curly phenotype during postnatal development in a process that may be mediated by multiple molecular signals. DNA methylation plays important roles in mammalian cellular processes and is essential for the initiation of hair follicle (HF) development. Here, we sought to investigate the effects of genome-wide DNA methylation by combining expression profiles of the underlying curly fleece dynamics. Genome-wide DNA methylation maps and transcriptomes of skin tissues collected from 45- to 108-day-old goats were used for whole-genome bisulfite sequencing (WGBS) and RNA sequencing, respectively. Between the two developmental stages, 1,250 of 3,379 differentially methylated regions (DMRs) were annotated in differentially methylated genes (DMGs), and these regions were mainly related to intercellular communication and the cytoskeleton. Integrated analysis of the methylome and transcriptome data led to the identification of 14 overlapping genes that encode crucial factors for wool fiber development through epigenetic mechanisms. Furthermore, a functional study using human hair inner root sheath cells (HHIRSCs) revealed that, one of the overlapping genes, platelet-derived growth factor C (PDGFC) had a significant effect on the messenger RNA expression of several key HF-related genes that promote cell migration and proliferation. Our study presents an unprecedented analysis that was used to explore the enigma of fleece morphological changes by combining methylome maps and transcriptional expression, and these data revealed stage-specific epigenetic changes that potentially affect fiber development. Furthermore, our functional study highlights a possible role for the overlapping gene PDGFC in HF cell growth, which may be a predictable biomarker for fur goat selection.

Sequence Characterization of DSG3 Gene to Know Its Role in High-Altitude Hypoxia Adaptation in the Chinese Cashmere Goat.

The Tibetan cashmere goat is one of the main goat breeds used by people living in the plateau. It exhibits the distinct phenotypic characteristics observed in lowland goats, allowing them to adapt to the challenging conditions at high altitudes. It provides an ideal model for understanding the genetic mechanisms underlying high-altitude adaptation and hypoxia-related diseases. Our previous exome sequencing of five Chinese cashmere breeds revealed a candidate gene, DSG3 (Desmoglein 3), responsible for the high-altitude adaptation of the Tibetan goat. However, the whole DSG3 gene (44 kbp) consisting of 16 exons in the goat genome was not entirely covered by the exome sequencing. In this study, we resequenced all the 16 exons of the DSG3 gene in ten Chinese native goat populations. Twenty-seven SNP variants were found between the lowland and highland goat populations. The genetic distance (FST ) of significant SNPs between the lowland and highland populations ranged from 0.42 to 0.58. By using correlation coefficient analysis, linkage disequilibrium, and haplotype network construction, we found three non-synonymous SNPs (R597E, T595I, and G572S) in exon 5 and two synonymous SNPs in exons 8 and 16 in DSG3. These mutations significantly segregated high- and low-altitude goats in two clusters, indicating the contribution of DSG3 to the high-altitude hypoxia adaptation in the Tibetan goat.