Genome-wide association study for cashmere traits in Inner Mongolia cashmere goat population reveals new candidate genes and haplotypes.

BACKGROUND: The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. RESULTS: We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109-1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05). CONCLUSIONS: In conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat.

Application of growth models to South African Boer goat castrates and does under feedlot conditions.

Mathematical models may aid researchers in describing biological processes, like growth, in animals. This study aimed to collect the body weight data of 18 Boer goat castrates and 20 Boer goat does, from birth until maturity, to model growth and determine growth trends. This is a novel investigation as sufficient information on an age-weight database for these two Boer goat sexes from birth to maturity, is lacking. Using age-weight data, four nonlinear models, namely the Brody, Gompertz, Logistic and Von Bertalanffy growth models, were plotted and evaluated. The model parameters of each growth model were compared for differences between the two sexes. The statistical effectiveness of fit was determined for each model using AIC and RMSE, with R2 also being considered. All models except the Brody model, predicted significantly heavier mature weights for castrates. The Brody model was deemed unfit to describe Boer goat growth as the function severely over-predict weights from birth until maturity for both sexes. The Von Bertalanffy (R2 = 91.3) and Gompertz functions (R2 = 91.3) showed the best fit for Boer goat castrates, while the Gompertz model (R2 = 95.1) showed the best fit for Boer goat does. The Gompertz function is the preferred model to depict Boer goat growth overall, as it accurately characterized growth of both sexes. According to the Gompertz model the age at which the inflection point of the growth curve was reached, did not differ significantly between castrates and does (141.80 days versus 136.31 days). There was also no significant difference in maturation rate between the two sexes.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Selection signatures in goats reveal copy number variants underlying breed-defining coat color phenotypes.

Domestication and human selection have formed diverse goat breeds with characteristic phenotypes. This process correlated with the fixation of causative genetic variants controlling breed-specific traits within regions of reduced genetic diversity, so called selection signatures or selective sweeps. Using whole genome sequencing of DNA pools (pool-seq) from 20 genetically diverse modern goat breeds and bezoars, we identified 2,239 putative selection signatures. In two Pakistani goat breeds, Pak Angora and Barbari, we found selection signatures in a region harboring KIT, a gene involved in melanoblast development, migration, and survival. The search for candidate causative variants responsible for these selective sweeps revealed two different copy number variants (CNVs) downstream of KIT that were exclusively present in white Pak Angora and white-spotted Barbari goats. Several Swiss goat breeds selected for specific coat colors showed selection signatures at the ASIP locus encoding the agouti signaling protein. Analysis of these selective sweeps revealed four different CNVs associated with the white or tan (AWt), Swiss markings (Asm), badgerface (Ab), and the newly proposed peacock (Apc) allele. RNA-seq analyses on skin samples from goats with the different CNV alleles suggest that the identified structural variants lead to an altered expression of ASIP between eumelanistic and pheomelanistic body areas. Our study yields novel insights into the genetic control of pigmentation by identifying six functionally relevant CNVs. It illustrates how structural changes of the genome have contributed to phenotypic evolution in domestic goats.

PAX7 promotes CD49f-positive dairy goat spermatogonial stem cells' self-renewal.

Spermatogenesis is a complex process that originates from and depends on the spermatogonial stem cells (SSCs). The number of SSCs is rare, which makes the separation and enrichment of SSCs difficult and inefficient. The transcription factor PAX7 maintains fertility in normal spermatogenesis in mice. However, for large animals, much less is known about the SSCs' self-renewal regulation, especially in dairy goats. We isolated and enriched the CD49f-positive and negative dairy goat testicular cells by magnetic-activated cell sorting strategies. The RNA- sequencing and experimental data revealed that cells with a high CD49f and PAX7 expression are undifferentiated spermatogonia in goat testis. Our findings indicated that ZBTB16 (PLZF), PAX7, LIN28A, BMPR1B, FGFR1, and FOXO1 were expressed higher in CD49f-positive cells as compared to negative cells and goat fibroblasts cells. The expression and distribution of PAX7 in dairy goat also have been detected, which gradually decreased in testis tissue along with the increasing age. When the PAX7 gene was overexpressed in dairy goat immortal mGSCs-I-SB germ cell lines, the expression of PLZF, GFRα1, ID4, and OCT4 was upregulated. Together, our data demonstrated that there is a subset of spermatogonial stem cells with a high expression of PAX7 among the CD49f+ spermatogonia, and PAX7 can maintain the self-renewal of CD49f-positive SSCs.

Spatial and temporal organization of jejunal microbiota in goats during animal development process.

AIMS: This research aimed to investigate the temporal bacterial colonization relating to non-rumination, transition and rumination phases, together with the spatial organization of microbial community in the jejunal mucosa and digesta of goats. METHODS AND RESULTS: This study explored the colonization programme of the jejunal microbiota by employing 16S rRNA amplicon sequencing. The colonization pattern of jejunal bacterial community exhibited an age- and gut region-dependent progression during animal development process. Approximately 268 bacterial signatures contributed to the discrimination between gut regions, with Lactobacillus, Ruminococcus, Eubacterium and Clostridium_sensu_stricto were enriched in the jejunal digesta, and Bacteroides and unclassified bacteria were enriched in the jejunal mucosa. Intriguingly, a shift from Lactobacillus to Butyrivibrio, Eubacterium and Ruminococcus after d 20 was observed for jejunal digesta. In mucosa, Bifidobacterium, Corynebacterium, Faecalibacterium and Roseburia increased with age (P < 0·05) while Arcobacter, Bacteroides and Porphyromonas peaked at d 10. CONCLUSIONS: The jejunal bacterial community was settled after solid starter provision, which may mark the potential boundary of a timeframe for intervention in goats. The spatial heterogeneity highlighted the complicacy of ecological niches during manipulation of gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study extended the understanding of microbial programming and niche specific in the jejunum among different life stages and the basal cognition of persistent enhancement of nutrient utilization and decline of enteric diseases in ruminants.

Genome-wide selection signal analysis of Australian Boer goat reveals artificial selection imprinting on candidate genes related to muscle development.

As one of the best-known commercial goat breeds in the world, Boer goat has undergone long-term artificial selection for nearly 100 years, and its excellent growth rate and meat production performance have attracted considerable worldwide attention. Herein, we used single nucleotide polymorphisms (SNPs) called from the whole-genome sequencing data of 46 Australian Boer goats to detect polymorphisms and identify genomic regions related to muscle development in comparison with those of 81 non-specialized meat goat individuals from Europe, Africa, and Asia. A total of 13 795 202 SNPs were identified, and the whole-genome selective signal screen with a π ratio of nucleotide diversity (πcase /πcontrol ) and pairwise fixation index (FST ) was analyzed. Finally, we identified 1741 candidate selective windows based on the top 5% threshold of both parameters; here, 449 candidate genes were only found in 727 of these regions. A total of 433 genes out of the 449 genes obtained were annotated to 2729 gene ontology terms, of which 51 were directly linked to muscle development (e.g., muscle organ development, muscle cell differentiation) by 30 candidate genes (e.g., JAK2, KCNQ1, PDE5A, PDLIM5, TBX5). In addition, 246 signaling pathways were annotated by 178 genes, and two pathways related to muscle contraction, including vascular smooth muscle contraction (ADCY7, PRKCB, PLA2G4E, ROCK2) and cardiac muscle contraction (CACNA2D3, CASQ2, COX6B1), were identified. The results could improve the current understanding of the genetic effects of artificial selection on the muscle development of goat. More importantly, this study provides valuable candidate genes for future breeding of goats.

SNP screening of the MSTN gene and correlation analysis between genetic polymorphisms and growth traits in Dazu black goat.

The aim of this study was to detect SNPs in myostatin (MSTN) gene of four goat breeds, and analyze the correlation of these markers on body measurement traits in the Dazu black goat breed. In total, twenty polymorphic sites were found in one hundred forty-eight individuals, and all SNPs were distributed in introns 1 and 2, except g. 425 C > T, which was found in the regulatory region. Three SNPs (g. 2732 C > T, g. 2752 G > A and g. 4552 A > C) were polymorphic in all four breeds. None of the tag SNPs (g. 425 C > T, g. 1583 A > G, 2732 C > T, g. 4552 A > C and g. 5167 C > T) were significantly correlated with body measurement traits (p > 0.05) in the Dazu black goat. However, individuals with genotype combination 3 (GtC 3) of tag SNPs had higher birth weight and weaning weight than individuals with the other genotype combinations (p < 0.05). Moreover, the genotype combination 4 (GtC 4) was significantly associated with body length and height at the age of 2 months (p < 0.05), and genotype combination 13 (GtC 13) was significantly correlated with body height at 6 months (p < 0.05). Briefly, the combined tag SNP markers might be useful for goat marker-associated selective breeding.

A novel duplicated insertion/deletion (InDel) of the CPT1a gene and its effects on growth traits in goat.

Carnitine palmitoyltransferase 1a (CPT1a) is a rate-limited enzyme in the mitochondrial fatty acid ß-oxidation pathway. It acts as a bridge between PPARα and the fatty acid oxidation pathways and is closely related to ruminant growth and development. In this study, one 12 bp InDel polymorphism of the CPT1a gene was identified in 700 goats, and we designated these three genotypes II, ID, and DD. Association analysis showed that the InDel polymorphism was closely associated with trunk index (p = 0.008) and body length index (p = 0.034) in Hainan black goats, and body length (p = 0.010), chest circumference (p = 0.004), chest depth (p = 0.029), and huckle bone width (p = 0.002) in Nubian goats, as well as the chest circumference (p = 0.016) in the Fuqing goat breed. In both kids and adult goats, qRT-PCR results showed that the CPT1a gene was expressed in all tissues, showing the highest mRNA levels in the liver, lung, spleen, and kidney, followed by the adipose tissue and brain. This indicates an association between the InDel of the CPT1a gene and growth traits in selected goat breeds, which may facilitate marker-assisted selection in goat genetics and breeding.

Detection of insertions/deletions (InDels) within the goat Runx2 gene and their association with litter size and growth traits.

Runt-related transcription factor 2 (Runx2) is characterized by its critical functions in osteoblastic and ovulatory processes. The goal of this study was to explore the insertion/deletion (indel) variants of this gene and to evaluate their association with productive traits. Herein, a 12 bp and 6 bp insertion within the Runx2 gene was uncovered in Shaanbei white cashmere goats (SBWC; n = 1200). Chi-square analysis revealed that the 12 bp insertion was related to litter size (p < 0.01). Further association analysis also found this insertion was significantly associated with litter size (p = 1.1E-5). Interestingly, this insertion was also significantly associated with chest circumference (p = 0.018). Additionally, the 6 bp insertion was associated with body length (p = 0.003), chest width (p = 0.011), and chest circumference (p = 0.005). Furthermore, diplotype associations also uncovered that the combined genotypes of these two indels also significantly affected litter size and growth traits (p < 0.05). These findings suggested that these two insertions within the Runx2 gene were significantly associated with reproduction and growth traits, which would make them beneficial functional DNA markers that can be used in goat breeding.

Influence of maternal and additive genetic effects on offspring growth traits in Beetal goat.

The purpose of the present study was to obtain estimates of variance components and genetic parameters for direct and maternal effects on various growth traits in Beetal goat by fitting four animal models, attempting to separate direct genetic, maternal genetic and maternal permanent environmental effects under restricted maximum likelihood procedure. The data of 3,308 growth trait records of Beetal kids born during the period from 2004 to 2019 were used in the present study. Based on best fitted models, the direct additive h2 estimates were 0.06, 0.27, 0.37, 0.17 and 0.10 for birth weight (BWT), weight at 3 (WT3), 6 (WT6), 9 (WT9) and 12 (WT12) months of age, respectively. Maternal permanent environmental effects significantly contributed for 10% and 7% of total variance for BWT and WWT, respectively, which reduced direct heritability by 40 and 10% for respective traits from the models without these effects. For average daily gain (ADG1) and Kleiber ratios (KR1) up to weaning period (3 months) traits, maternal permanent environmental effects accounted for 7% and 8% of phenotypic variance, respectively, and resulted in a reduction of 6.6% and 5.4% in direct h2 of respective traits. For post-weaning traits, the maternal effects were non-significant (p > .05) which indicates diminishing influence of mothering ability for these traits. High and positive genetic correlations were obtained among WT3-WT6, WT6-WT9 and WT9-WT12 with correlations of 0.96 ± 0.25, 0.84 ± 0.23 and 0.90 ± 0.13, respectively. Thus, early selection at weaning age can be practised taking into consideration maternal variation for effective response to selection in Beetal goat.

Genome-wide CNV analysis revealed variants associated with growth traits in African indigenous goats.

Using the CaprineSNP50 data generated by the AGIN consortium, we detected common CNVs in 126 samples from four African indigenous goat breeds. A total of 30 CNVs ranging from 30,237 bp to 4,910,757 bp were identified. These CNVs were then associated with six growth traits by a linear regression analysis. Three significant associations were identified between two CNVs and two body traits after false discovery rate (FDR) correction (P < .05). One of them (CNV27) was significantly associated with both chest width and width of pin bones. It overlaps the SNX29 gene, the Gene Ontology (GO) annotations of which indicate CNV27 could be a potential functional candidate for meat production, health and reproduction traits. To our knowledge, this study is the first CNV-based association test of growth traits using SNP chip data in African meat goats.

Evaluation of non-linear models for growth curve in Brazilian tropical goats.

In the present study, 1060 body weight-age records were measured on 300 Canindé goats. The records were collected from Rio Grande do Norte state, North-eastern part of Brazil, and used for evaluation of non-linear models (Brody, Von Bertalanffy, Logistic, and Gompertz) describing growth curve in goats. The non-linear models were compared applying mean squared error of prediction (MSEP), mean squared residue (MSR), mean absolute deviation (MAD), adjusted coefficient of determination (R2aj), and convergence percentage (%C) for determining the most appropriate model describing the growth curve in Canindé goats. The absolute growth rate (AGR) was estimated based on the adjusted model as a function of time to describe the growth rate of the animals, and the effect of sex on the curve parameters was assessed. The Brody model was the most indicated to represent the average growth curve of Canindé goats. Furthermore, the growth curves estimated by the models under study show that the Brody model displayed the best fit, indicating a greater association between observed and estimated weights, suggesting that it can be used to describe the growth behavior and development of the animals analyzed of both sexes.

Genetic analysis of sexual size dimorphism in Markhoz goat.

Genetic bases of sexual size dimorphism (SSD) in Markhoz goat (5268 kids descended from 242 sires and 1499 dams) were unraveled as it was thought that sex-specific genetic mechanism is in the place governing SSD of birth weight (BW), weaning weight at 90 days of age (WW_90d), and post-weaning weights at 6 (W6), 9 (W9), and 12 (W12) months of age. Male kids excelled for BW, WW_90d, W6, W9, and W12 than their female counterparts in the tune of 10, 17, 14, 17, and 23%, respectively. Estimates of sexual dimorphism levels (expressed as M/F) were 1.09, 1.17, 1.14, 1.17, and 1.23 for BW, WW_90d, W6, W9, and W12, respectively, which indicated relatively low levels of sexual size dimorphism in the studied traits. Though the additive genetic, residual and phenotypic variances were higher in males than females, for mostly all studied traits, but the heritability estimates for all traits except birth weight were higher in females. Differences in direct and maternal effects between male and female kids indicated that body weights traits could be treated as separate trait for male and female kids. Cross-sex genetic correlations revealed that almost all ages, genetic correlations between the two sexes, were high, and the lowest estimate (0.88) was for W6, which highlighted this trait as the most dimorphic trait in this breed. High and positive genetic correlations between the sexes indicated that selection for body weight in males would result in a correlated response in females and vice versa and, consequently, would prevent phenotypic divergence.

Effects of king grass and sugarcane top in the absence or presence of exogenous enzymes on the growth performance and rumen microbiota diversity of goats.

In the present study, the feasibility of sugarcane top (ST) application in the goat's diet was evaluated. A total of 20 goats were randomly divided into four groups. The dietary treatments were set as follows: animals were fed with king grass (KG), KG with exogenous enzymes (KGE), ST, and ST with exogenous enzymes (STE). The animals were given free access to feed and water. After 15 days of adaptation and 60 days of the experiment, the growth performance, plasma parameters, and rumen microbiota of goats were assessed. The results showed that the KG, ST, and exogenous enzyme supplement had no significant effects on the growth performance and plasma parameters. The diet affected the rumen microbiota diversity and structure, and the alpha and beta diversity in the animals fed with ST were dramatically greater compared with the animals fed with KG. The abundances of Proteobacteria, Cyanobacteria, and Elusimicrobia were significantly decreased in the animals fed with KG or KGE, while the abundances of Firmicutes and Euryarchaeota were significantly higher in the animals fed with KG or KGE. Furthermore, the microbial communities were also different at the genus level. Moreover, the exogenous enzymes had a slight effect on rumen microbiota. Linear discriminant analysis effect size (LEfSe) analysis showed that the greatest differences were found in bacterial taxa, and these specific taxa could be used as biomarkers to distinguish rumen microbiota. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional profile prediction indicated that the dietary treatments of ST and KG could also alter the gene expression pattern in nutrient and energy metabolism, as well as replication and repair of genetic information pathways. Collectively, the dietary treatments of KG and ST in the absence or presence of exogenous enzymes had similar effects on the growth performance and plasma parameters of goats. Besides, the KG and ST diets could affect the rumen microbiota community and function of goats. Therefore, ST could be used as a promising alternative feed resource for ruminants without the addition of exogenous enzymes in tropical regions.

miR-34a/c induce caprine endometrial epithelial cell apoptosis by regulating circ-8073/CEP55 via the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways.

microRNAs (miRNAs) and circular RNAs (circRNAs) are important for endometrial receptivity establishment and embryo implantation in mammals. miR-34a and miR-34c are highly expressed in caprine receptive endometrium (RE). Herein, the functions and mechanisms of miR-34a/c in caprine endometrial epithelial cell (CEEC) apoptosis and RE establishment were investigated. miR-34a/c downregulated the expression level of centrosomal protein 55 (CEP55) and were sponged by circRNA8073 (circ-8073), thereby exhibiting a negative interaction in CEEC. miR-34a/c induced CEEC apoptosis by targeting circ-8073/CEP55 through the regulation of the RAS/RAF/MEK/ERK and phosphoitide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways. Positive and negative feedback loops and cross-talk were documented between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. miR-34a/c regulated the levels of RE marker genes, including forkhead box M1, vascular endothelial growth factor, and osteopontin (OPN). These results suggest that miR-34a/c not only induce CEEC apoptosis by binding to circ-8073 and CEP55 via the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways, but may also regulate RE establishment in dairy goats.

Chi-miR-30b-5p inhibits dermal papilla cells proliferation by targeting CaMKIIδ gene in cashmere goat.

BACKGROUND: During goat embryonic morphogenesis and postnatal initiation of hair follicle (HF) regeneration, dermal papilla (DP) cells play a vital role in hair formation. Growing evidence shows that microRNAs (miRNAs) participate in HF development and DP cell proliferation. However, the molecular mechanisms have not been thoroughly investigated. RESULT: In this study, we utilized miRNA sequencing (miRNA-Seq) to identify differentially expressed miRNAs at different HF cycling stages (anagen and telogen). MiRNA-Seq has identified 411 annotated miRNAs and 130 novel miRNAs in which 29 miRNAs were up-regulated and 32 miRNAs were down-regulated in the anagen phase compared to the telogen phase. Target gene prediction and functional enrichment analysis indicated some major biological pathways related to hair cycling, such as Wnt signaling pathways, ECM-receptor interaction, VEGF signaling pathway, biosynthesis of amino acids, metabolic pathways, ribosome and oxidative phosphorylation. Also, we explored the function of chi-miR-30b-5p in regulating hair growth cycle. Similar to the HF cycling, DP cells were isolated from skin and used to investigate miRNA functions. The MTT and EdU assays showed that the viability and proliferation of DP cells were inhibited or promoted after the transfection of chi-miR-30b-5p mimic or inhibitor, respectively. Bioinformatics analysis revealed CaMKIIδ as a candidate target gene of chi-miR-30b-5p, and the dual-luciferase and western blot assay demonstrated that chi-miR-30b-5p bound to the 3'UTR of CaMKIIδ and further inhibited its translation. CONCLUSION: Chi-miR-30b-5p was found to be highly expressed in the telogen than that in the anagen phase and could inhibit the proliferation of DP cells by targeting CaMKIIδ. Our study provides new information on the regulatory functions of miRNAs during HF development.

Systematic analyses reveal RNA editing events involved in skeletal muscle development of goat (Capra hircus).

RNA editing is a posttranscriptional molecular process involved with specific nucleic modification, which can enhance the diversity of gene products. Adenosine-to-inosine (A-to-I, I is read as guanosine by both splicing and translation machinery) is the main type of RNA editing in mammals, which manifested as AG (adenosine-to-guanosine) in sequence data. Here, we aimed to explore patterns of RNA editing using RNA sequencing data from skeletal muscle at four developmental stages (three fetal periods and one postnatal period) in goat. We found the occurrences of RNA editing events raised at fetal periods and declined at the postnatal period. Also, we observed distinct editing levels of AG editing across stages, and significant difference was found between postnatal period and fetal periods. AG editing patterns in newborn goats are similar to those of 45-day embryo compared with embryo at 105 days and embryo at 60 days. In this study, we found a total of 1415 significantly differential edited AG sites among four groups. Moreover, 420 sites were obviously clustered into six time-series profiles, and one profile had significant association between editing level and gene expression. Our findings provided some novel insights into understanding the molecular mechanism of muscle development in mammals.

Effects of dietary supplementation with different concentration of molasses on growth performance, blood metabolites and rumen fermentation indices of Nubian goats.

BACKGROUND: Molasses is a potential energy supplement; extensively used to improve growth performance, milk and meat characteristics in goats at relatively low concentrations of 5-40% of the diet. Few data are available concerning feeding molasses to goat kids; therefore, the current study aimed to investigate the effects of dietary supplementation with higher concentrations of molasses on growth performance, blood metabolites and rumen fermentation indices. Twenty male Nubian goat kids (4-6 months old; 9-10 kg BW) were randomly assigned to 4 groups receiving different concentration of molasses: 0% (M-0), 30% (M-30), 40% (M-40) and 45% (M-45) for 5 weeks. Feed (DFI) and water intake (DWI) were measured daily, while the blood and rumen liquor samples were collected weekly. RESULTS: The DFI increased and feed conversion ratio (FCR) decreased in all molasses-supplemented groups (P ≤ 0.05), whereas DWI increased in M-30 and decreased in M-45 (P ≤ 0.05). The final BW and average daily gain (ADG) increased (P < 0.0001) in groups M-30 and M-40 compared to the control and M-45. Blood pH was significantly influenced by dietary molasses concentration (MC) and the duration of molasses supplementation (MD), where it decreased in groups M-30 and M-45 compared to the control and M-40 (P < 0.05). The MC had no significant effect on blood Hb, HCT, TLC, albumin, [K+], AST, ALT and total protozoa count (TPC), as well as ruminal-[Na+], [K+], strong ion difference concentration ([SID3]) and [NH3]; however, only [NH3] was significantly affected by MD and the interaction between MC and MD (MC × MD). Serum TP, globulins, [Na+] and [Cl-] increased (P ≤ 0.05) in all supplemented groups, while A/G ratio and [SID3] decreased (P ≤ 0.05). Ruminal pH decreased (P < 0.0001) in M-40 and M-45 compared to the control and M-30. However, [VFAs] increased (P < 0.04) in M-30 and M-40 compared to the control and M-45, while osmolality increased (P ≤ 0.05) in M-30 compared to the other groups. CONCLUSIONS: Dietary supplementation with molasses at a concentration of 30% for 3 weeks improved growth performance, protein metabolism and rumen fermentation without compromising animal health, immunity, and electrolytes and acid-base homeostasis.

InDels within caprine IGF2BP1 intron 2 and the 3'-untranslated regions are associated with goat growth traits.

Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) is involved in the Hedgehog pathway and has been shown to regulate the RNA stability of several growth-related target genes. It is located in a quantitative trait locus showing a strong association with traits related to body size in ducks. Fibroblast growth factor receptor 1 (FGFR1) also participates in Hedgehog signaling pathways and has been reported to be associated with organic growth and development. FGFR1-knockout mice have been shown to have severe postnatal growth defects, including an approximately 50% reduction in body weight and bone mass. Meanwhile, nonsense-mediated mRNA decay factor (SMG6) can maintain genomic stability, which is associated with organic growth and development. Therefore, we hypothesized that IGF2BP1, FGFR1 and SMG6 genes may play important roles in the growth traits of goats. In this study, the existence of two insertion/deletion (InDel) variants within IGF2BP1, one InDel within FGFR1 and two InDels within SMG6 was verified and their correlation with growth traits was analyzed in 2429 female Shaanbei white cashmere goats. Results showed both the 15 bp InDel in intron 2 and the 5 bp InDel in the 3' regulatory region within IGF2BP1 were significantly associated with growth traits (P < 0.05) and goats with the combinatorial homozygous insertion genotypes of these two loci had the highest body weight (P = 0.046). The other InDels within FGFR1 and SMG6 were not obviously associated with growth traits (P > 0.05). Therefore, the two InDels in IGF2BP1 were vital mutations affecting goat growth traits.