Low-Coverage Whole-Genome Sequencing Identifies Loci Associated with Birth Weight in East Friesian × Hu Crossbred Sheep

Birth weight is a key early-life trait in sheep that influences neonatal survival and subsequent growth, but its genetic basis remains incompletely understood. Here, we used low-coverage whole-genome sequencing (lcWGS)-based genotyping and genome-wide association analysis (GWAS) to investigate birth weight in 671 East Friesian × Hu crossbred lambs, achieving high imputation accuracy (98.5% allelic concordance). A total of 148 SNPs reached the suggestive significance threshold, of which 20 reached genome-wide significance. Among these signals, the chromosome 7 locus contained 69 suggestive variants spanning an approximately 6 kb interval within the SPATA7 region, including 14 genome-wide significant SNPs. Notably, 13 of these suggestive variants overlapped annotated enhancer intervals, of which 3 reached genome-wide significance. Portions of the associated interval also coincided with pituitary ATAC-seq and liver H3K4me1 ChIP-seq signals. Chr7:98,178,889 A > G, the most strongly associated SNP in this region, showed birth-weight differences among genotypes. Lambs carrying the AG genotype had significantly higher adjusted least-squares mean birth weight than AA lambs (3.81 vs. 3.56 kg; Δ = 0.25 kg, +7.0%). These findings prioritize the SPATA7 region as a candidate regulatory locus for birth-weight variation and provide a basis for future fine-mapping and functional validation.