Jul 2026· Genomics· Vol 118, pp.
111295
· 0 citations
Medicine
TL;DR
It is suggested that DNMT3A may regulate rabbit growth via mediating DNA methylation of downstream genes through mediating DNA methylation of downstream genes.
Abstract
The parameters of individual growth curve can serve as pseudo-phenotype for genetic evaluation in livestock. In this study, we compared five nonlinear growth models using post-weaning body weights of 706 New Zealand White rabbits. Under the best-fitting model, two parameters of mature weight and maturity rate were subjected to GWAS through single-step genomic BLUP framework that integrated phenotypic records from non-genotyped animals with 41,359 SNPs genotyped in 198 individuals. Association analysis identified 147 relevant genomic regions, and also highlighted DNMT3A as a promising candidate gene for further functional investigation. siRNA-mediated knockdown of DNMT3A significantly impaired myoblast proliferation. Whole-genome bisulfite sequencing of DNMT3A-knockdown myoblasts identified 69,480 differentially methylated regions (DMRs). Integrative analyses revealed substantial overlap between DMR-associated genes and GWAS candidate genes, with significant enrichment in vitamin B6 and tyrosine metabolism pathways. These findings suggest that DNMT3A may regulate rabbit growth via mediating DNA methylation of downstream genes.
Hu sheep are a well-known Chinese dual-purpose breed valued for meat production, early sexual maturity, high prolificacy, and adaptability to hot, humid environments. In this study, we combined whole-genome sequencing, GWAS, and eQTL analyses to investigate the genetic basis of growth and slaughter traits in 420 eight-month-old Hu sheep. Using a discovery cohort (
N
= 112) and a validation cohort (
N
= 308), we integrated high-throughput SNP genotyping and RNA sequencing, identifying 559,996 high-quality SNPs and multiple significant loci associated with traits such as live weight and carcass weight. Among the 2,368 cis-eQTLs detected, the most significant was linked to
ZNF280B
expression in the longissimus lumborum muscle. Functional validation showed that
ZNF280B
downregulation significantly inhibited skeletal muscle satellite cell proliferation and induced apoptosis, highlighting its critical role in muscle development and fat metabolism. The novelty of this study lies in its large sample size, comprehensive multi-trait analysis, and the integration of functional validation, providing reliable genetic markers for marker-assisted selection in Hu sheep. These findings deepen our understanding of the genetic mechanisms underlying growth and slaughter performance and offer valuable insights for improving production efficiency and promoting sustainable livestock development.
Body size is a key economic trait influencing the profitability of farmed animals. This study used genome-wide association studies (GWAS) to identify five single nucleotide polymorphisms (SNPs) significantly associated with body size in the Tibetan sheep population, advancing molecular breeding and providing a basis for genomic selection. These SNPs are located within five candidate genes. SNaPshot validated GWAS results, demonstrating significant correlations between candidate SNPs and body size traits in Tibetan sheep. Concurrently, hematoxylin and eosin staining, alongside muscle fiber analysis, confirmed pronounced morphological differences in muscle tissue between sheep of varying conformation. Therefore, transcriptome and proteomics were performed on the longest dorsi muscle from large and small Tibetan sheep of both sexes. The transcriptome, together with weighted gene co-expression network analysis (WGCNA), identified VEPH1 and PRKG1 as core genes regulating body characteristics in Tibetan sheep through their involvement in the PI3K-Akt signaling pathway and pathways related to fat deposition. The integrative analyses demonstrated significantly different expression of CARNS1 and CRYAB at both transcriptional and protein levels between the muscles of large- and small-sized Tibetan sheep of both sexes, suggesting their importance in body size traits by influencing muscle morphology. This study provides valuable genomic resources that advance sheep genetics research.
Target gene prediction and enrichment analysis indicated that pre-miR-1453 may participate in the regulation of chicken growth and serum biochemical parameters through pathways related to neuron development, cytoskeletal dynamics, and energy metabolism.
Jianzhou Shi, Lunguang Yao, G. Sun· Animals· 0 citations
Objective
Litter size is a key trait for evaluating reproductive performance of goats, which can directly influence the breeding efficiency and profitability of production cycles. However, a comprehensive understanding of its genetic architecture, including the causative mutations and their functional impacts, remains scarce, thus hindering its application in precision breed-ing.
Methods
A total of 92 female Leizhou goats were genotyped through whole-genome se-quencing (WGS), and their litter size were measured for three consecutive births. Subsequently, based on the genotype and phenotype data, population genetic structure analysis, selection signature analysis, and genome-wide association study (GWAS) were performed.
Results
We identified a total of 20,802,514 SNPs in the 92 Leizhou goats. Analysis of genetic structure revealed that the high-litter-size group exhibited greater genetic diversity than the low-litter-size group, although no significant genetic differentiation was detected between them. We identified 340 putative selective regions and 346 candidate genes across the genome. A total of 37 candidate genes were identified as being closely associated with reproductive traits, including BMP6, MAPK8, RPTOR, etc. In GWAS results, we identified 63 quantitative trait loci (QTLs) for litter size at suggestive significance (P＜1×10-5). After, 207 candidate genes were annotated, and 4 of them were highlighted that have been previously reported to be associated with reproductive processes (e.g., TMEM100, PDGFD, NLRP9, and ARHGAP22). By integrating the results from both approaches, we identified MAPK8 as a potential candidate gene associated with litter size. Furthermore, our findings from motif recognition, transcrip-tion factor prediction, and previous studies lead us to propose that the BMP6-GATA4-MAPK8 signaling pathway may play a key role in regulating litter size in goats.
Conclusion
Our findings identify several candidate genes and putative associated variants for litter size, providing valuable insights into the genetic basis of reproductive traits in goats.
Da Feng, Siyi Hu, Jian Ma et al.· Animal bioscience· 0 citations
Structural variations (SVs) represent a significant source of genomic diversity, with demonstrated roles in livestock gene expression and traits. However, a comprehensive understanding of the SV landscape across large sample sets and its impact on gene regulation in cattle remains incomplete. This study aimed to construct high-fidelity pangenome graphs by integrating both assembly-based and whole-genome sequencing (WGS) derived SV catalogs. We evaluated the efficacy of pangenome graphs for SV genotyping and identified 80,328 high-quality SVs from a cohort of 2929 samples. We systematically characterized these SVs, including their linkage disequilibrium with single nucleotide polymorphisms (SNPs), functional annotations, formation mechanisms, and genomic distributions. Furthermore, we generated paired WGS (24.4 ×) and blood RNA-seq data in 170 Simmental cattle. Utilizing our pangenome graphs, we identified 637 SV-expression quantitative trait loci (SV-eQTL), which accounted for 10.81% of expression heritability of target genes, with 38.09% of the effects linked to promoter/enhancer regions. Forty-six of these SV-eQTL were replicated using CattleGTEx results through SV imputation using a joint SNP-SV reference panel. Notably, insertions in the GHSR gene were significantly associated with its expression levels, likely linked to Bos indicus cattle adaptation to heat tolerance. Our findings provide novel insights into the SV landscape and its contribution to gene regulation, underscoring its importance in cattle genetics and genomics.
