Fine mapping genetic variants affecting birth weight in sheep: a GWAS of 3007 individuals using low-coverage whole genome sequencing

作者：Ran Li, Yuheng Bai, Maqiang Zhao, Xinyue Zhang, Haiyan Wang, Bo Feng, Shuo Zhang, Huanhuan Zhang, Gang Ren, Xihong Wang, Yu Jiang · 发表于：Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · 年份：2025 · DOI：10.1186/s40104-025-01251-4 · 被引用次数：7 · 研究领域：Genetic and phenotypic traits in livestock、Genetic Mapping and Diversity in Plants and Animals、Genetic Associations and Epidemiology

BACKGROUND: Birth weight is a critical economic trait in livestock production. However, its genetic architecture remains poorly understood due to historical limitations in sample size and reliance on low-density SNP arrays. In this study, we utilized low-coverage whole-genome sequencing (lcWGS) to genotype 3,007 Hu sheep, bypassing the cost and resolution constraints of conventional genotyping arrays while achieving scalable genome-wide variant detection. RESULTS: LcWGS with high imputation accuracy (97.8% allelic concordance) enabled genome-wide association studies (GWAS) identifying two novel quantitative trait loci (QTLs) on chromosomes 6 and 9. The chromosome 9 QTL encompassed a regulatory region functionally linked to PLAG1 expression through expression quantitative trait locus (eQTL) mapping. Compared with wild-type homozygotes, heterozygous carriers of the lead SNP (chr9:g.35920172A > G) presented a 9.85% increase in birth weight (3.35 kg vs. 3.68 kg; Δ = 0.33 kg). Notably, the derived allele of this SNP exhibited low frequencies of < 0.1 across most global sheep breeds except Dorper, highlighting its potential for selective breeding applications. Leveraging lcWGS data, haplotype-based fine-mapping prioritized three candidate causal variants. A secondary QTL on chromosome 6 colocalized with the FecB mutation, a well-established locus associated with increased litter size. Intriguingly, individuals carrying one FecB allele showed a 6.18% reduction (0.22 kg) in birth wei...