The genetic landscape of the human solute carrier (SLC) transporter superfamily

In this study, we analyzed Next-Generation Sequencing data from 141,456 individuals from seven major human populations to evaluate genetic variability, its functional consequences, and ethnogeographic patterns across the entireSLC superfamily of transporters. Importantly, of the 204,287 exonic single-nucleotide variants (SNVs) which we identified, 99.8% were present in less than 1% of analyzed alleles. Comprehensive computational analyses using 13 partially orthogonal algorithms that predict the functional impact of genetic variations based on sequence information, evolutionary conservation, structural considerations, and functional genomics data revealed that each individual genome harbors 29.7 variants with putative  functional effects, of which rare variants account for 18%. Inter-ethnic variability was found to be extensive, and 83% of deleterious SLC variants were only identified in a single population. Interestingly, population-specific carrier frequencies of loss-of-function variants inSLC genes associated with recessive Mendelian disease recapitulated the ethnogeographic variation of the corresponding disorders, including cystinuria in Jewish individuals, type II citrullinemia in East Asians, and lysinuric protein intolerance in Finns, thus providing a powerful resource for clinical geneticists to inform about population-specific prevalence and allelic composition of MendelianSLC diseases. In summary, we present the most comprehensive data set ofSLC variability publi...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research