A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Stokowski, Renee; Pant, Poonam; Dadd, Tony; Fereday, A.; Hinds, David A.; Jarman, Carl; Filsell, Wendy; Ginger, Rebecca S.; Green, Martin R.; Ouderaa, Frans J. van der; Cox, David

doi:10.1086/522235

Cited by 268 publications

(267 citation statements)

References 55 publications

(88 reference statements)

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“…G176A and G176C, resulted in mutant NCKX2 proteins with greatly reduced but measurable functional activity (Ͻ10% of WT activity) (35, 39). With respect to the NCKX4 A142T substitution, the homologous A111T substitution in both alleles of the human SLC24A5 gene was shown to be a major determinant of light skin in people from European descent (18,19). The homologous A177T substitution in NCKX2 reduced activity to ϳ25% of WT NCKX2 activity (27), consistent with the reduction of the A142T NCKX4 mutant reported here (ϳ23% of WT NCKX4).…”

Section: Discussionsupporting

confidence: 68%

See 1 more Smart Citation

A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism

Jalloul

Rogasevskaia

Szerencsei

et al. 2016

Journal of Biological Chemistry

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transport activity of WT and mutant NCKX4 proteins expressed in HEK293 cells. Three mutant NCKX4 cDNAs represent mutations found in the SCL24A4 gene and three represent mutations found in the SCL24A5 gene involving residues conserved between NCKX4 and NCKX5. Five mutant proteins had no observable NCKX activity, whereas one mutation resulted in a 78% reduction in transport activity. Total protein expression and trafficking to the plasma membrane (the latter with one exception) were not affected in the HEK293 cell expression system. We also analyzed two mutations in a Drosophila NCKX gene that have been reported to result in an increased susceptibility for seizures, and found that both resulted in mutant proteins with significantly reduced but observable NCKX activity. The data presented here support the genetic analyses that mutations in SLC24A4 and SLC24A5 are responsible for the phenotypic defects observed in human patients.

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Section: Discussionsupporting

confidence: 68%

“…Another member of the NCKX family, the SLC24A5 gene has been shown to be the major genetic determinant of light skin in people from European descent (18,19), and three distinct SLC24A5 mutations have been linked to oculocutaneous albinism (OCA6) (20,21). Fig.…”

Section: Slc24a4mentioning

confidence: 99%

A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism

Jalloul

Rogasevskaia

Szerencsei

et al. 2016

Journal of Biological Chemistry

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“…[4][5][6][7] The various ethnic groups on Madagascar are generally classified into two main subgroups: the Highlanders (HL), considered being more Asian in culture and phenotype, and the people from the coasts (CT), thought to be more African. 8 The determination of the phenotype, for example, eye colour, hair colour or skin colour, or the population origin from DNA has been an important research field in recent years, in which considerable progress has been accomplished (see for example [9][10][11][12][13][14][15] ). These techniques have already been applied successfully in the characterisation of ancient skeletal human remains.…”

Section: Introductionmentioning

confidence: 99%

Determination of population origin: a comparison of autosomal SNPs, Y-chromosomal and mtDNA haplogroups using a Malagasy population as example

Poetsch¹,

Wiegand²,

Harder³

et al. 2013

Eur J Hum Genet

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Y-chromosomal and mitochondrial DNA (mtDNA) polymorphisms have been used for population studies for a long time. However, there is another possibility to define the origin of a population: autosomal single-nucleotide polymorphisms (SNPs) whose allele frequencies differ considerably in different populations. In an attempt to compare the usefulness of these approaches we studied a population from Madagascar using all the three mentioned approaches. Former investigations of Malagasy maternal (mtDNA) and paternal (Y chromosome) lineages have led to the assumption that the Malagasy are an admixed population with an African and Asian-Indonesian heritage. Our additional study demonstrated that more than two-third of the Malagasy investigated showed clearly a West African genotype regarding only the autosomal SNPs despite the fact that 64% had an Asian mtDNA and more than 70% demonstrated an Asian-Indonesian heritage in either mtDNA or Y-chromosomal haplogroup or both. Nonetheless, the admixture of the Malagasy could be confirmed. A clear African or Asian-Indonesian heritage according to all the three DNA approaches investigated was only found in 14% and 1% of male samples, respectively. Not even the European or Northern African influences, detected in 9% of males (Y-chromosomal analysis) and 11% of samples (autosomal SNPs) were consistent. No Malagasy in our samples showed a European or Northern African origin in both categories. So, the analysis of autosomal SNPs could confirm the admixed character of the Malagasy population, even if it pointed to a greater African influence as detectable by Y-chromosomal or mtDNA analysis.

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“…Using large populations with mostly Caucasian individuals, GWAS have produced sufficient evidence of the genetic associations with BCC risk (Stokowski et al, 2007;Sulem et al, 2007;Brown et al, 2008;Han et al, 2008;Stacey et al, 2008;Sulem et al, 2008;Falchi et , 2009b;Rafnar et al, 2009;Stacey et al, 2009;Duffy et al, 2010). However, a paucity of studies based on data from non-Caucasian deals with the genetic associations with BCC risk (Cho et al, 2001;Kim et al, 2002;Kang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Exploratory Investigation of Genetic Associations with Basal Cell Carcinoma Risk: Genome-Wide Association Study in Jeju Island, Korea

Yun

Song²,

Lee³

2014

Asian Pacific Journal of Cancer Prevention

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Aim: Little is known about the genetic associations with Basal cell carcinoma (BCC) risk in non-Caucasian populations, in which BCC is rare, as in Korea. We here conducted a pilot genome-wide association study (GWAS) in 12 patients and 48 standard controls. Method: A total of 263,511 SNPs were analyzed with the Illumina HumanOmni1 Quad v1.0 DNA Analysis BeadChip for cases and Korean HapMap 570K for controls. Results: SNP-based analyses, based on the allele genetic model with adjustment for sex and age showed suggestive associations with BCC risk for 6 SNPs with a P-value (P < 0.0005). However, these associations were not statistically significant after Bonferroni correction: rs1040503, rs2216491, rs13407683, rs4751072, rs9891263, and rs1368474. In addition, results from gene-based analyses showed suggestive associations with BCC risk for 33 candidate genes with a P-value (P <0.0005). Consistent with previous GWAS and replication studies in Caucasian populations, PADI6, RHOU and SLC45A2 were identified as having null associations with BCC (P > 0.05), likely due to the smaller sample size. Conclusions: Although this was a small-scale negative study, to our knowledge, we have conducted the first GWAS for BCC risk in an Asian population. Further large studies in non-Caucasian populations are required to achieve statistical significance and confirm these findings.

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A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Cited by 268 publications

References 55 publications

A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism

A Functional Study of Mutations in K+-dependent Na+-Ca2+ Exchangers Associated with Amelogenesis Imperfecta and Non-syndromic Oculocutaneous Albinism

Determination of population origin: a comparison of autosomal SNPs, Y-chromosomal and mtDNA haplogroups using a Malagasy population as example

Exploratory Investigation of Genetic Associations with Basal Cell Carcinoma Risk: Genome-Wide Association Study in Jeju Island, Korea

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