Promoter polymorphisms in the<i>MATP</i>(<i>SLC45A2</i>) gene are associated with normal human skin color variation

Graf, Justin T.; Voisey, Joanne; Hughes, Ian; Daal, Angela M. van

doi:10.1002/humu.20504

Cited by 67 publications

(55 citation statements)

References 28 publications

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“…2A; Duffy et al 2007;Sulem et al 2007;Sturm et al 2008). Multiple hits were also found in other known pigmentation genes in the top 1000 associated SNPs: TYR, TYRP1 and top 10,000: SLC24A4, SLC24A5 (see Supplemental Table S1; Graf et al 2007;Stokowski et al 2007;Sulem et al 2007). …”

Section: Resultsmentioning

confidence: 89%

Rapid inexpensive genome-wide association using pooled whole blood

Craig¹,

Hewitt²,

McMellon³

et al. 2009

Genome Res.

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Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large data sets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls, respectively, is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time. This method has profound implications for translation of modern genetic approaches to a multitude of diseases and traits yet to be analyzed by GWAS, and will enable developing nations to participate in GWAS.

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Section: Resultsmentioning

confidence: 89%

Rapid inexpensive genome-wide association using pooled whole blood

Craig¹,

Hewitt²,

McMellon³

et al. 2009

Genome Res.

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“…Similar to the main pigmentation genes, MITF also regulates tyrosinase, TYRP1 and DCT [12]. SLC45A2 expression may also be affected by polymorphisms in the MITF promoter [31]. Huang et al introduced a mutation in the structure of SLC45A2 protein (threonine 32 was replaced with serine, T32S) to mimic a human ortholog, potentially changing the function of the corresponding protein and further affecting the phenotype.…”

Section: Discussionmentioning

confidence: 99%

Distribution and expression of SLC45A2 in the skin of sheep with different coat colors

Wang

et al. 2016

Folia Histochem Cytobiol.

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Introduction. To investigate whether the membrane-associated transporter protein SLC45A2 is differentially expressed in the skin of sheep with different coat colors and to determine its correlation with coat color establishment in sheep. Material and methods. The expression of SLC45A2 in sheep skin samples with different coat colors was qualitatively and quantitatively analyzed by PCR amplification, RT-PCR, immunohistochemical staining and Western blotting. Results. A 193-bp SLC45A2 CDS sequence was successfully amplified from sheep skin samples with diverse coat colors. RT-PCR analysis revealed that SLC45A2 mRNA was expressed in all sheep skin samples tested, with relative expression levels of 512.74 ± 121.51 in black skin, 143.38 ± 119.31 and 1.36 ± 0.09 in black dots and white dots of piebald skin, respectively, and 1.02 ± 0.23 in white skin (p < 0.01**). Positive SLC45A2 protein bands were also detected in all skin samples by Western blot analysis, with relative expression levels of 0.85 ± ± 0.17** in black skin, 0.60 ± 0.05** and 0.34 ± 0.07 in black dots and white dots of piebald skin, respectively, and 0.20 ± 0.05 in white skin (p < 0.01**). Immunohistochemical assays revealed that SLC45A2 was expressed in the hair follicle matrix, the inner and outer root sheath, and the dermal papilla in the skin tissues with different coat colors. These patterns were quantified by optical density (OD) analysis, which yielded relative expression levels of 0.23 ± 0.11 in black skin, 0.19 ± 0.09 and 0.10 ± 0.03 in black dots and white dots of piebald skin, respectively, and 0.08 ± 0.01 in white skin (p < 0.05*). Conclusion. SLC45A2 is detectably expressed in sheep skin of all coat colors, though at significantly different levels. SLC45A2 may participate in the establishment of coat color by regulating the synthesis and trafficking of melanin.

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“…We here compare the observed F ST value to the distribution of F ST values obtained in simulations under the previously estimated demographic model. Strikingly, the second most significant gene is SLC45A2, which has previously been shown to account for part of the variation in human skin color (Graf et al 2005(Graf et al , 2007. Only the allele frequencies of TRAF2 differ more between the two populations.…”

Section: Increased Population Subdivision (F St )mentioning

confidence: 98%

Darwinian and demographic forces affecting human protein coding genes

Nielsen¹,

Hubisz²,

Hellmann³

et al. 2009

Genome Res.

144

158

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Past demographic changes can produce distortions in patterns of genetic variation that can mimic the appearance of natural selection unless the demographic effects are explicitly removed. Here we fit a detailed model of human demography that incorporates divergence, migration, admixture, and changes in population size to directly sequenced data from 13,400 protein coding genes from 20 European-American and 19 African-American individuals. Based on this demographic model, we use several new and established statistical methods for identifying genes with extreme patterns of polymorphism likely to be caused by Darwinian selection, providing the first genome-wide analysis of allele frequency distributions in humans based on directly sequenced data. The tests are based on observations of excesses of high frequency-derived alleles, excesses of low frequency-derived alleles, and excesses of differences in allele frequencies between populations. We detect numerous new genes with strong evidence of selection, including a number of genes related to psychiatric and other diseases. We also show that microRNA controlled genes evolve under extremely high constraints and are more likely to undergo negative selection than other genes. Furthermore, we show that genes involved in muscle development have been subject to positive selection during recent human history. In accordance with previous studies, we find evidence for negative selection against mutations in genes associated with Mendelian disease and positive selection acting on genes associated with several complex diseases.

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Promoter polymorphisms in theMATP(SLC45A2) gene are associated with normal human skin color variation

Cited by 67 publications

References 28 publications

Rapid inexpensive genome-wide association using pooled whole blood

Rapid inexpensive genome-wide association using pooled whole blood

Distribution and expression of SLC45A2 in the skin of sheep with different coat colors

Darwinian and demographic forces affecting human protein coding genes

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