Application of evolutionary based in silico methods to predict the impact of single amino acid substitutions in vitelliform macular dystrophy.

Recent developments in high-throughput discovery and genotyping have generated a tremendous amount of information about the existence of single amino acid polymorphisms (SAPs). Detailed understanding of the SAPs that affect protein structure and function can provide us valuable insight into disease genotype-phenotype correlations. Functional variants of biological importance are likely to be missed in large-scale analysis. Over the past decade, numerous efforts are underway in understanding and characterizing the potential consequences of variants in assessing the risk associated with vitelliform macular dystrophy (VMD). Yet, in spite of this success, we conducted a first SAP analysis via evolutionary-based in silico pipeline to unravel functional SAPs from a pool, containing both functional and neutral ones. Furthermore, based on the prediction scores, a ranking system was developed to prioritize the functional SAPs in order to minimize the number of SAPs screened for further genotyping.

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