Fine mapping genetic variants affecting birth weight in sheep:a GWAS of 3007 individuals using low-coverage whole genome sequencing
摘要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(IcWGS)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 encom-passed 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;△=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 selec-tive breeding applications.Leveraging IcWGS 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 weight,which tentatively indicates potential pleiotropic influences on both growth and reproductive traits.Conclusion This study demonstrates the utility of IcWGS as a cost-effective,high-resolution tool for dissecting complex traits in livestock.Our findings not only advance the understanding of birth weight genetics in sheep but also offer a blueprint for accelerating genetic improvement programs in global livestock production through cost-effective,genome-wide approaches.
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