title: A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene.
abstract: Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2.
authors.affiliation: Department of Production and Characterization of New Foods, Institute of Food Science Research (CIAL), UAM-CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Marín-Martín
authors.affiliation: Department of Production and Characterization of New Foods, Institute of Food Science Research (CIAL), UAM-CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Soler-Rivas
authors.affiliation: IMDEA Food Institute, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Martín-Hernández
authors.affiliation: IMDEA Food Institute, Campus de Cantoblanco, 28049 Madrid, Spain ; Nutritional Genomics of the Cardiovascular Disease and Obesity, IMDEA Food Institute, Carretera Cantoblanco 8, 28049 Madrid, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Rodriguez-Casado