Evaluation of MC1R high-throughput nucleotide sequencing data generated by the 1000 Genomes Project

Abstract

The advent of next-generation sequencing allows simultaneous processing of several genomic regions/individuals, increasing the availability and accuracy of whole-genome data. However, these new approaches may present some errors and bias due to alignment, genotype calling, and imputation methods. Despite these flaws, data obtained by next-generation sequencing can be valuable for population and evolutionary studies of specific genes, such as genes related to how pigmentation evolved among populations, one of the main topics in human evolutionary biology. Melanocortin-1 receptor (MC1R) is one of the most studied genes involved in pigmentation variation. As MC1R has already been suggested to affect melanogenesis and increase risk of developing melanoma, it constitutes one of the best models to understand how natural selection acts on pigmentation. Here we employed a locally developed pipeline to obtain genotype and haplotype data for MC1R from the raw sequencing data provided by the 1000 Genomes FTP site. We also compared such genotype data to Phase 3 VCF to evaluate its quality and discover any polymorphic sites that may have been overlooked. In conclusion, either the VCF file or one of the presently described pipelines could be used to obtain reliable and accurate genotype calling from the 1000 Genomes Phase 3 data.

Genetic diversity of the melanocortin-1 receptor in an admixed population of Rio de Janeiro: Structural and functional impacts of Cys35Tyr variant

“…This work characterized the entire coding region of melanocortin 1 (MC1R) receptor gene in an admixed population from Southeast of Brazil. The MC1R is widely studied in humans and non-humans and several variants have been described to influence melanin production [16]. We detected 31 different polymorphisms comprehending synonymous, nonsynonymous substitutions and indels, which agrees with the notion that the MC1R is considered a polymorphic gene [54].…”

“…Initially, studies on MC1R were based on individuals of unmixed origin who tend to have low intrapopulation skin color variation. However, few studies have been conducted in order to understand the genetic diversity and the phenotypic associations that comprise the intermediate levels between low and high melanin production, requiring further investigation in admixed populations [15][16][17]. Brazil is considered one of the most genetically diversified and highly admixed populations [18].…”

Transcriptome assembly and polymorphism detection in Silene ciliata (Caryophyllaceae)

“…SNPs were identified using Reads2snp (Gayral et al ., 2013) and filtered with VCFtools 4.1 (Danecek et al ., 2011). Only, biallelic SNPs with no missing data and at least seven reads per genotype were retained to prevent the inclusion of false positive SNPs (Swarts et al ., 2014; Marano et al ., 2017). Paralogous and singleton SNPs were further deleted.…”

Mutations in G Protein–Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches

“…In some cases, heterozygosity can drift or even confer potential selective advantages to mutation carriers over a long period, as in the case of prokineticin receptor type 2 (PROKR2), in which the inactivating mutation L173R has persisted more than 9000 years (Avbelj Stefanija et al, 2012). A high frequency of inactivating mutations in populations may indeed have an advantage as suggested for variants in the melanocortin type 1 receptor (MC1R) gene, a key regulator of melanogenesis (Martínez-Cadenas et al, 2013;Dib et al, 2017;Marano et al, 2017).…”