IRF2BP2 genes provide new insights into coat type and fiber composition variation in sheep

Since the domestication of sheep ( Ovis aries ), coat type has undergone selective breeding from double to single coats. The IRF2BP2 gene contains significant polymorphisms that affect fleece structure in sheep. This study investigates two such variants: a ~1.5 kb antisense EIF2S2 retrotransposon insertion ( asEIF2S2 ) in the 3'-UTR and a T7068586C single nucleotide polymorphism (SNP) found on chromosome 25 ( Oar_rambouillet_v1.0 ). We analyzed 692 ewes from single-coated (Chinese Merino: CM; German Meat Merino: GM; Suffolk: SFK), double-coated (Hetian: HT; Kazakh: KZK), and Texel × Kazakh hybrid (TKH) populations. Genotyping analysis demonstrated a complete association between the asEIF2S2 insertion and coat type, with this insertion being fixed in all single-coated breeds. The T7068586C SNP, polymorphic only in double-coated breeds, was significantly associated with the non-medullated fiber ratio (NMFR) in Kazakh sheep. In the segregating TKH population, both loci exhibited highly significant additive effects on fiber traits. The asEIF2S2 insertion increased NMFR by 9.69% and decreased hair fiber diameter (HFD) by 2.69 µm per allele. The T7068586C C allele showed even stronger effects, increasing NMFR by 10.62% and decreasing HFD by 2.27 µm per allele. Critically, analysis of two-locus combinations identified the ++/CC genotype as optimal, yielding the highest NMFR (83.04%) and the finest fibers. IRF2BP2 expression in skin was negatively correlated with NMFR, supporting its role as a transcriptional repressor of wool development. These results demonstrate that the asEIF2S2 insertion is a major determinant of the single/double coat transition, while the T7068586C SNP acts as a key modifier of fiber composition. The ++/CC haplotype provides a powerful molecular tool for marker-assisted selection to enhance fleece homogeneity and quality in sheep breeding. • asEIF2S2 insertion in IRF2BP2 3' UTR perfectly associates with sheep coat type. • Texel×Kazakh hybrids segregate all locus genotypes, an ideal model for dissecting effects. • The double-homozygous ++/CC genotype combination emerges as the most desirable, associated with a high ratio of non-medullated fibers and low fiber diameter. • Identified allelic variations give new insights into sheep fleece variation population history.