Signatures of selection detected from whole-genome sequencing indicate that the small body size in dwarf rabbit breeds is caused by polygenic effects with a few major loci

Abstract

Early genetic studies have suggested that body size in rabbits can be considered a quantitative trait. Several rabbit breeds can be distinguished based on body size, including a few dwarf breeds differentiated by other morphological characteristics. While a large deletion in the HMGA2 gene is a major locus associated with dwarfism in Netherland Dwarf rabbits, it may not fully explain the reduced body size in this breed or other dwarf breeds. In this study, we compared the genomes of two dwarf rabbit breeds (Dwarf Lop and Netherland Dwarf) with those of non-dwarf rabbits by analysing whole-genome sequencing data obtained using a DNA-pool sequencing approach. We applied the fixation index (F_ST) and pooled heterozygosity (H_P) statistics to identify signatures of selection related to small body size by contrasting dwarf with non-dwarf breeds and comparing dwarf breeds. We identified several genomic regions that contain genes previously linked to body dimensions in various species, including LCORL-NCAPG, COL2A1, GHRHR and CENPE. Functional enrichment analysis of genes within the top differentiated regions revealed biological terms related to skeletal development, further supporting the biological relevance of these loci. Additionally, the use of the latest version of the reference rabbit genome enabled the identification of a genomic region containing FGFR3, a gene linked to achondroplasia. Some genomic regions showed differentiation between the two dwarf breeds, suggesting that their small body size may, in part, arise through different genetic mechanisms. Overall, these findings support a polygenic architecture underlying small size in rabbits, influenced by a few major loci.