Association of genetic variants with skin pigmentation phenotype among populations of west Maharashtra, India

Abstract

Only rs1426654 is significantly associated with MI in each individual population; however, rs1426654, rs1042602, and rs16891982 are significantly associated with pigmentation in the broader West Maharashtra region after controlling for population and social group, with rs1426654 (SLC24A5) explaining the majority of the observed variation. Am. J. Hum. Biol. 28:610-618, 2016. © 2016 Wiley Periodicals, Inc.

Identification of a novel locus associated with skin colour in African-admixed populations

“…This gene is located in the 15q21.1 chromosomal band and encodes the NCKX5 protein (solute carrier family 24 [sodium/potassium/calcium exchanger], member 5), an intracellular membrane protein whose function has been associated with skin colour and diseases related to skin pigmentation2148. The top SNP in our meta-analysis (rs1426654) has been also associated with skin colour in African American and African Caribbean populations in a candidate-gene study21, and has broadly replicated across different populations181920232445.…”

“…These SNPs are located within three genomic regions. Two regions are already known to contribute to skin colour, including SLC24A5 181920212345 and surrounding genes (Supplementary Fig. S3) as well as the SLC45A2 182445 gene (Supplementary Fig.…”

“…However, candidate-gene and genome-wide association studies (GWAS) have revealed only a few of the total estimated number of genes implicated in the variability of human skin colour21415. Moreover, despite the large differences in skin pigmentation across populations, most genetic association studies of skin colour have been performed in European1617 and Asian populations181920. Only a handful of candidate-gene association studies has been performed in African ancestry populations14212223, and one lone GWAS has been carried out in African-European admixed individuals from Cape Verde24.…”

SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation

“…membrane associated transporter protein, MATP or antigen isolated from immunoselected melanoma-1, AIM1) (Newton, Cohen-Barak et al, 2001). Mutations in the homologous gene underlie pigment dilution in a number of vertebrate species, including gorilla, several breeds of dog, tigers, horses, mice, shrew, chickens, pigeons, quail, frogs, fish and perhaps cattle (Caduff, Bauer et al, 2017, DeLay, Corkins et al, 2018, Domyan, Guernsey et al, 2014, Dooley, Schwarz et al, 2013, Fukamachi, Shimada et al, 2001, Gunnarsson, Hellström et al, 2007, Mariat, Taourit et al, 2003, Minvielle, Cecchi et al, 2009, Newton et al, 2001, Prado-Martinez, Hernando-Herraez et al, 2013, Rothammer, Kunz et al, 2017, Tsetskhladze, Canfield et al, 2012, Tsuboi, Hayashi et al, 2009, Wijesena & Schmutz, 2015, Winkler, Gornik et al, 2014, Xu, Dong et al, 2013, and polymorphisms at the SLC45A2 locus are associated with skin tone differences and skin aging in several human population studies (Adhikari et al, 2019, Branicki et al, 2008, Cerqueira, Hunemeier et al, 2014, Fracasso, de Andrade et al, 2017, Han et al, 2008, Jonnalagadda, Norton et al, 2016, Law, Medland et al, 2017, Liu et al, 2015, Lopez, Garcia et al, 2014, Soejima & Koda, 2007, Stokowski et al, 2007, Yuasa, Umetsu et al, 2006. OCA4 patients have very low levels of pigmentation and phenotypically resemble OCA2 patients who lack the melanosomal chloride channel, OCA2 (Bellono, Escobar et al, 2014), suggesting that SLC45A2 plays an important role in melanogenesis (Montoliu et al, 2014).…”

“…Differences in skin and hair pigmentation among European, Chinese, South American and South Asian human populations have been ascribed to a single genetic variant in SLC45A2 associated with the SNP rs16891982. This encodes a single amino acid change at position 374leucine (L374) in dark skinned individuals and phenylalanine (F374) in light skinned individuals (Adhikari et al, 2019, Branicki et al, 2008, Cerqueira et al, 2014, Han et al, 2008, Jonnalagadda et al, 2016, Liu et al, 2015, Lopez et al, 2014, Soejima & Koda, 2007, Stokowski et al, 2007, Yuasa et al, 2006; this residue lies within the 8th predicted transmembrane domain of SLC45A2 (Newton et al, 2001).…”