A genome wide association study for diarrhea resistance in pre-weaned rabbits identified markersuseful to breed for increased animal welfare.

Animal welfare and reduction of antimicrobial agents are gaining more and more importance in defining sustainable livestock production systems. Adopting novel breeding and selection strategies that directly or indirectly address these aspects can also improve efficiency and farmers’ profitability. In commercial rabbitries, diarrhea of newborn rabbits represents one of the major sources of economic losses. Genetic resistance against diarrhea can be dissected using genomic approaches. In this study, we carried out a case-control genome-wide association study for identifying genomic regions affecting the sensitivity to pre-weaning diarrhea in a commercial rabbit population. Animals included in the study were from litters produced by crossing 7 bucks and 45 does. A total of 331 newborn rabbits (149 healthy and 182 with diarrhetic) were selected from litters presenting at least one case and one control animal. Genotyping of the selected rabbits was carried out with the Affymetrix Axiom OrcunSNP Array, which analyse a total of 199,692 single nucleotide polymorphisms (SNPs). PLINK v.1.9 was used for quality checks and data filtering whereas association was carried out with GEMMA v.0.98 via linear mixed models. A main peak of association was identified on rabbit chromosome 12. Results were further validated by genotyping the associated DNA markers in additional cases and controls from another cohort of the same rabbit population. Fine mapping of the region based on whole genome resequencing data obtained from a few cases and controls identified a few candidate causative mutations in genes involved in basic immunological functions. The genomic information here obtained will be useful for implementing a marker assisted selection program aimed at improving resistance against pre-weaning diarrhea and improving animal welfare and the sustainability of the rabbit production system.