Comprehensive in Silico Analyses of Single Nucleotide Variants of the Human Orthologues of 171 Murine Loci to Seek Novel Insights into the Genetics of Human Pigmentation

Modulations in melanin synthesis and distribution caused by underlying genetic variants are considered to be majorly responsible for the inter-personal human pigmentation variation. In the publicly available Color Genes dataset, 171 cloned murine loci are documented to be involved with alterations in mice coat color. We hypothesize that the human orthologues of these 171 loci may also be implicated towards human pigmentation variation through their polymorphic variants. We used several freely available bioinformatic tools and designed a predictive pipeline to prioritize the Single Nucleotide Variants (SNVs) within and in the vicinity of the 171 human orthologues, according to their functional potential. The genes associated with the prioritized SNVs were annotated a potential function in the pigmentation pathway, based on extensive literature review and assessment of protein–protein interaction networks. Our analyses could prioritize 77 candidate SNVs including 10 non-synonymous SNVs, 45 synonymous SNVs and 22 regulatory SNVs associated with 46 genes that can potentially contribute towards human pigmentation variation. Our study, thus outlines a comprehensive bioinformatic pipeline using freely available web-tools that can be utilized in similar kind of studies dealing with other complex human traits and diseases where individual nucleotide variant imparts subtle functional roles in regulating the phenotype.