Genome-wide association study reveals genes crucial for coat color production in Vrindavani cattle.

• We have identified genes by GWAS which are involved in well-established MAPK and PI3K-AKT signalling pathways, affecting biochemical process of coat colour production. • Due to introduction of exotic blood to continue the process of development of Vrindavani cattle, a very low F ST value was observed suggesting outbreeding of the population. • This work provides a preliminary information to carry forward researches on genomic basis of coat colour patterns in crossbred cattle Coat colour and various patterns are the hallmarked qualitative traits studied in cattle as well as other livestock; however, variation in this trait is resultant of interactions and epistasis of a set of genes rather than being a product of a single gene. In this study, GWAS has been conducted from 50K SNP genotype data, with a stratified approach on Vrindavani cattle (n=48). The study was conducted in two sets of an experiment wherein set I treats all the solid colours (n=18) as controls and rest spotted or patchy types as cases (n=30), and set II treats brown and brown with white spots as controls (n=15), and rest as cases (n=33). After quality check (MAF>0.01, genotyping rate>90%, and H-W equilibrium at p≤ 0.001) of genotype data, 37247 SNPs were further used for accomplishing Genome-Wide Association Study (GWAS) with coat colour. The distinct phenotypes were classified into four different sub-groups that are solid black, black with white patches, solid brown, and brown with white patches along with greyish white. The allele frequency difference was checked in all sub-groups. The GWAS was conducted in PLINK v1.7 and for graphical representation R was used. Two SNPs in set I and 20 in set II were found to be significantly associated with coat colour in Vrindavani cattle. A ±500 Kb genome scan around the significant SNPs revealed gene BDNF for SNP DIAS-217 in set I and FGF18 for SNP ARS-BFGL-NGS-105192, and CACNA2D1 , and HGF for SNP BTB-01885061 in set II, are present around these SNPs. In KEGG-based pathway enrichment analysis, all the above-mentioned genes were found to be involved in well-established MAPK and PI3K-AKT signalling pathways, affecting the biochemical process of coat colour production. Genome-wide F ST values were low to moderate across the genome, however few associated SNPs had moderate to high F ST values indicating their power in differentiating the subgroups according to coat colour phenotype. This study provides a preliminary report of markers and genes involved in coat colour expression and revealed that the reported genes around the associated SNPs are involved in brown with white spotting phenotype. However, further researches in this field are essential for a more conclusive result. [ABSTRACT FROM AUTHOR]