Genome wide association analysis on semen volume and milk yield using different strategies of imputation to whole genome sequence in French dairy goats.

BACKGROUND: Goats were domesticated 10,500 years ago to supply humans with useful resources. Since then, specialized breeds that are adapted to their local environment have been developed and display specific genetic profiles. The VarGoats project is a 1000 genomes resequencing program designed to cover the genetic diversity of the Capra genus. In this study, our main objective was to assess the use of sequence data to detect genomic regions associated with traits of interest in French Alpine and Saanen breeds.

RESULTS: Direct imputation from the GoatSNP50 BeadChip genotypes to sequence level was investigated in these breeds using FImpute and different reference panels: within-breed, all Capra hircus sequenced individuals, European goats and French mainland goats. The best results were obtained with the French goat panel with allele and genotype concordance rates reaching 0.86 and 0.75 in the Alpine and 0.86 and 0.73 in the Saanen breed respectively. Mean correlations tended to be low in both breeds due to the high proportion of variants with low frequencies. For association analysis, imputation was performed using FImpute for 1129 French Alpine and Saanen males using within-breed and French panels on 23,338,436 filtered variants. The association results of both imputation scenarios were then compared. In Saanen goats, a large region on chromosome 19 was significantly linked to semen volume and milk yield in both scenarios. Significant variants for milk yield were annotated for 91 genes on chromosome 19 in Saanen goats. For semen volume, the annotated genes include YBOX2 which is related to azoospermia or oligospermia in other species. New signals for milk yield were detected on chromosome 2 in Alpine goats and on chromosome 5 in Saanen goats when using a multi-breed panel.

CONCLUSION: Even with very small reference populations, an acceptable imputation quality can be achieved in French dairy goats. GWAS on imputed sequences confirmed the existence of QTLs and identified new regions of interest in dairy goats. Adding identified candidates to a genotyping array and sequencing more individuals might corroborate the involvement of identified regions while removing potential imputation errors.