The high mobility group AT-hook 2 (HMGA2) allele associated with the dwarf phenotype segregates in various rabbit breeds but is not carried by all dwarf and small body sized rabbits

• The high mobility AT-hook 2 ( HMGA2 ) allele associated with the dwarf phenotype was investigated in several rabbit breeds. • The mutated allele has high frequency in two out of three dwarf rabbit breeds investigated. • This allele is under balancing selection in two dwarf breeds: Coloured Dwarf and Ermine/Hermelin. • The mutated allele also segregates in Dwarf Lop and several small-bodied breeds, but with low frequencies. • Fancy rabbit breeders should use genotyping information to plan matings and avoid the harmful effect of this allele. Rabbit breeds are traditionally grouped into four major categories (dwarf, small, medium, and large) based on their adult weight. Dwarf and small rabbit breeds are highly valued due to the worldwide demand for these animals as pets. A deletion in the high mobility group AT-hook 2 ( HMGA2 ) gene was identified as a major determinant of dwarfism in rabbits, causing the dw allele at the Dwarf locus. Homozygous dw / dw rabbits, called peanuts, are not viable. In this study, the diffusion of the mutated HMGA2 allele was evaluated in 11 rabbit breeds classified as dwarf or small and three other breeds using a multiplex PCR assay. None of the 259 rabbits analysed were homozygous for the mutated HMGA2 allele. The mutated allele was found in two dwarf rabbit breeds (Coloured Dwarf and Ermine/Hermelin) with relatively high frequencies (∼30%), in one dwarf breed (Dwarf Lop) and in two small rabbit breeds (Dutch and Perl Feh) with lower frequencies (<10%). The mutated allele was likely under balancing selection in Coloured Dwarf and Ermine/Hermelin, with an excess of heterozygous individuals (∼60%) than what would be expected under Hardy-Weinberg equilibrium. However, as the mutated allele was not found in all dwarf rabbits, the small body size in rabbits can be achieved by combining polygenic effects from several other genomic regions, without relying on this defective allele. Therefore, rabbit breeders should consider this gene information to avoid matings that could produce non-viable rabbits. This approach would lead to more ethical and sustainable breeding programs.