Genome-wide association and pathwaybased analysis for milk fatty acids profile in dairy cattle

Fatty acids (FA) profile has a great impact on the nutritional and technological quality of milk and dairy products. Genome wide associations (GWAS) and gene-set enrichment analyses were conducted for 65 milk FA. Milk samples from 1152 Italian Brown Swiss cows reared in 85 herds were used. Animals were genotyped with the Illumina BovineSNP50 Bead Chip v.2. A single marker regression model was applied for GWAS using the GenABEL R package and the GRAMMAR-GC approach. A gene-set enrichment analysis was run on GWAS results, using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases, to reveal ontologies/pathways associated with the phenotypes of interest. In total 175 SNPs were significant (p<5x10-5) spanning all Bos taurus autosomes (BTAs). The highest signals were detected on BTA26 (~22.98 Mbp) and on BTA8 (~3.66 Mbp). Four sub-regions were detected on BTA26 associated with 8 traits. The region 26a corresponded to only 1 SNP (~9.87 Mbp) which was associated to both C10:1 and C14:1 indices. The regions 26b, 26c and 26d contained multiple SNPs. In particular, the region 26b included 4 SNPs (~14.66-16.71 Mbp) associated to C14:1 index and C14:1 cis-9. In the region 26c (~18.17-22.98 Mbp), signals were detected for C14:1 index, C10:1 index, C14:1 cis-9, monounsaturated FA, C18:1 cis-9, C10:0, C12:0 and C14:0. Finally, 6 SNP in the region 26d (~25.09-31.58 Mbp) were associated to C14:1 index and C14:1 cis-9. The high signal on BTA8 (Hapmap40047-BTA-119117) was significantly associated to C18:1 trans-16. Gene-set enrichment analyses showed significant results (Fisher’s exact test, false discovery rate <.05) for 20 FA traits. In particular, C12:0 was associated with the highest number of overrepresented categories/pathways,including several connected to the regulation of mitogen-activated protein kinase (MAPK) activity and protein phosphorylation. The considerably large number of enriched GO and KEGG terms for C12:0 suggested that such phenotype might have a relevant biological role in the regulation of processes affecting milk fat composition. These findings might be helpful for follow-up studies designed to shed more light into the molecular mechanisms underlying FA synthesis and metabolism in the bovine mammary gland. The new insights could contribute to set up selective breeding programs aiming to obtain a healthier milk FA composition. Acknowledgements The research was funded by Trento Province (Italy), the Italian Brown Swiss Cattle Breeders’ Association (ANARB,Verona, Italy), and the Superbrown Consortium of Bolzano and Trento.