Investigating genetic factors affecting a production disease in meat rabbits: a genome-wide association study on susceptibility to diarrhea before weaning

Ensuring animal welfare and reducing antimicrobial agents are becoming key aspects in the development of sustainable livestock production systems. The implementation and adoption of novel breeding and selection strategies that align with these aspects can enhance both production efficiency and farmers' profitability. As a result, sustainability and economic returns in livestock farming can be simultaneously improved, especially in the rabbit production system, where diseases like diarrhea in newborn rabbits represent a major source of economic losses. In this study, we aimed to genetically dissect the resistance against diarrhea by designing a case-control genome-wide association study (GWAS) to identify genetic markers affecting the sensitivity to this disease in a commercial meat rabbit population. The study included rabbits from 133 litters produced by crossing 7 bucks and 45 does. A total of 332 suckling rabbits were selected from 45 different litters, with 151 rabbits with severe symptoms of diarrhea, 42 with mild symptoms and 129 without any symptoms until weaning. Genotyping of these animals was done using the Affymetrix Axiom OrcunSNP Array, which interrogates a total of 199,692 single nucleotide polymorphisms (SNPs). The data obtained were quality checked and filtered using PLINK v.1.9 software. Genomic heritability (h2G) estimation of the trait was carried out with GEMMA v.0.98 software with linear mixed models. Genomic heritability estimates ranged from 0.19 to 0.21 (with standard error that ranged from 0.09 to 0.10). Three main peaks of SNPs were identified on rabbit chromosome 12 (OCU12), OCU13 and OCU16, with annotation of these genomic regions indicating genes involved in the innate immune system as potential candidates for this pathogenic condition. Results were validated by genotyping associated SNPs in additional cases and control animals from a different rabbit cohort of the same population. Fine mapping of these genomic regions was conducted by mining whole genome resequencing data obtained from several susceptible and resistant rabbits within the same litters, identifying a few candidate causative mutations. Overall, the results obtained in this genomic study demonstrate that resistance to enteropathy occurring in suckling rabbits is partially genetically determined and can be dissected at the genomic level. This information will be useful for implementing a marker assisted selection program aimed at improving resistance against pre-weaning diarrhea, animal welfare and the overall sustainability of the rabbit production system.