The economic efficiency of the sheep industry hinges significantly on reproductive performance, with litter size being a primary determinant [1]. Reproductive traits, typically characterized by low heritability, pose challenges for efficient phenotypic selection. Therefore, marker-assisted selection (MAS) has emerged as a practical strategy for the genetic improvement of reproductive efficiency. Notably, several major prolificacy genes including BMPR1B (bone morphogenetic protein receptor 1B), BMP15 (bone morphogenetic protein 15), and GDF9 (growth differentiation factor 9), have been reported in sheep [2,3]. Integrating knowledge on polymorphism in those major genes of high prolificacy can effectively inform targeted breeding schemes aimed at enhancing reproductive performance within specific production systems.

BMPR1B affects the ovine ovulation number via the BMP/SMAD pathway, which is a key pathway regulating mammalian follicle development [4]. As a member of the bone morphogenetic protein (BMP) receptor family, BMPR1B is highly expressed in follicles and corpora lutea at various developmental stages [5]. It can bind with the BMP ligand together with BMPR1A to form heterotetrameric complexes and initiate downstream SMAD proteins through a cascade of phosphorylation reactions [6]. The FecB mutation (Q249R) within BMPR1B is a pivotal functional variant influencing prolificacy in sheep. One copy of the FecB mutation (B+) increases the litter size by 0.9 lambs born per lambing on average [7]. Subsequent investigations have revealed the presence of the FecB mutation not only in Booroola Merino sheep but also in several other prolific breeds in India, China, and Iran [[8], [9], [10]]. However, unlike the Q249R locus, other polymorphisms within BMPR1B remain understudied. Only a few novel single nucleotide polymorphisms (SNPs) in the FecB gene have been identified, suggesting potentially significant implications [11]. These findings suggest a promising opportunity for future research involving the genotyping of BMPR1B gene polymorphisms associated with sheep litter size.

The aim of this study was to investigate the full spectrum of SNPs within the BMPR1B gene using whole genome sequence (WGS) data obtained from diverse sheep populations worldwide and to explore potentially novel variants associated with litter size. This study is the most comprehensive exploration of SNPs in the ovine BMPR1B gene to date, and leverages WGS data from 2409 individuals spanning 75 populations worldwide. The results of this study could greatly expand the understanding of the genetic control of reproductivity in sheep and provide candidate markers associated with litter size for potential integration into sheep breeding programs.