Implications of the Admixture Process in Skin Color Molecular Assessment

Abstract

The understanding of the complex genotype-phenotype architecture of human pigmentation has clear implications for the evolutionary history of humans, as well as for medical and forensic practices. Although dozens of genes have previously been associated with human skin color, knowledge about this trait remains incomplete. In particular, studies focusing on populations outside the European-North American axis are rare, and, until now, admixed populations have seldom been considered. The present study was designed to help fill this gap. Our objective was to evaluate possible associations of 18 single nucleotide polymorphisms (SNPs), located within nine genes, and one pseudogene with the Melanin Index (MI) in two admixed Brazilian populations (Gaucho, N = 352; Baiano, N = 148) with different histories of geographic and ethnic colonization. Of the total sample, four markers were found to be significantly associated with skin color, but only two (SLC24A5 rs1426654, and SLC45A2 rs16891982) were consistently associated with MI in both samples (Gaucho and Baiano). Therefore, only these 2 SNPs should be preliminarily considered to have forensic significance because they consistently showed the association independently of the admixture level of the populations studied. We do not discard that the other two markers (HERC2 rs1129038 and TYR rs1126809) might be also relevant to admixed samples, but additional studies are necessary to confirm the real importance of these markers for skin pigmentation. Finally, our study shows associations of some SNPs with MI in a modern Brazilian admixed sample, with possible applications in forensic genetics. Some classical genetic markers in Euro-North American populations are not associated with MI in our sample. Our results point out the relevance of considering population differences in selecting an appropriate set of SNPs as phenotype predictors in forensic practice.

Predicting Physical Features and Diseases by DNA Analysis: Current Advances and Future Challenges

“…The practical application of FDP technology requires robust validation protocols, but it is also necessary to account for population differences regarding the association of genetic markers used, as suggested by Cerqueira et al [69]. For example, although there are highly significant polymorphisms associated with a particular phenotype in some populations, these same PIMs have effects that are apparently too small or null in others, suggesting that they can only be used as markers in the context of specific populations.…”

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).…”

Estudo da diversidade dos genes MC1R e SLC24A5 em populações globais: avaliação de aspectos evolutivos e ambientais

“…O alelo 111Thr se apresentou correlacionado com a pigmentação clara em populações afro-americanas e afro-caribenhas miscigenadas (Sturm, 2006) e também na população brasileira (Cerqueira et al, 2014;De Araujo Lima et al, 2015) Apesar de alguns estudos mostrarem que esse polimorfismo pode resultar em modificações no pH do melanossomo, levando a alterações nas vias de síntese da melanina, Ginger et al (2008) (Nielsen et al, 2011). Diversas metodologias foram propostas neste contexto, incluindo, por exemplo, PCR em emulsão (454 -Roche, Ion Torrent -Life) e amplificação em fase sólida (SolexaIllumina) (Metzker, 2010;.…”