Anti-SLC45A2 monoclonal antibody, clone 2C3

Pigmentation is a readily scorable and quantitative human phenotype, making it an excellent model for studying multifactorial traits and diseases. Convergent human evolution from the ancestral state, darker skin, towards lighter skin colors involved divergent genetic mechanisms in people of European vs. East Asian ancestry. It is striking that the European mechanisms result in a 10-20-fold increase in skin cancer susceptibility while the East Asian mechanisms do not. Towards the mapping of genes that contribute to East Asian pigmentation there is need for one or more populations that are admixed for ancestral and East Asian ancestry, but with minimal European contribution. This requirement is fulfilled by the Senoi, one of three indigenous tribes of Peninsular Malaysia collectively known as the Orang Asli. The Senoi are thought to be an admixture of the Negrito, an ancestral dark-skinned population representing the second of three Orang Asli tribes, and regional Mongoloid populations of Indo-China such as the Proto-Malay, the third Orang Asli tribe. We have calculated skin reflectance-based melanin indices in 492 Orang Asli, which ranged from 28 (lightest) to 75 (darkest); both extremes were represented in the Senoi. Population averages were 56 for Negrito, 42 for Proto-Malay, and 46 for Senoi. The derived allele frequencies for SLC24A5 and SLC45A2 in the Senoi were 0.04 and 0.02, respectively, consistent with greater South Asian than European admixture. Females and individuals with the A111T mutation had significantly lighter skin (p = 0.001 and 0.0039, respectively). Individuals with these derived alleles were found across the spectrum of skin color, indicating an overriding effect of strong skin lightening alleles of East Asian origin. These results suggest that the Senoi are suitable for mapping East Asian skin color genes.

To perform molecular analysis of five Korean patients with oculocutaneous albinism (OCA) and review the clinical and genetic characteristics of 21 Korean OCA patients. TYR, OCA2 and SLC45A2 were analyzed by direct DNA sequencing in five unrelated OCA patients who received thorough ophthalmic evaluation. We identified three different TYR mutations in three patients (c.929dupC, R278X, and R52I), among which the latter two had been previously reported in other populations, but are reported here for the first time in a Korean context. In one patient we identified two different mutations of OCA2 [c.1784+1G > A and c.1842G > T (K614N)]. One patient was confirmed to have OCA4 by detecting two SLC45A2 mutations [c.469G > A (D157N) and c.686G > A (C229Y)]. OCA1A (66.7%) was the most common subtype in 21 Korean albinism patients, and 70% of patients were heterozygotes for 2 different mutational alleles. c.929dupC (54.8%) and R77Q (16.1%) were the most frequent mutational alleles of TYR in Koreans. Three mutational alleles, R278X and R52I of the TYR gene and C229Y of the SLC45A2 gene, are added to the mutational spectra of Korean patients with OCA, and we report the first Korean case of OCA2 with the OCA2 gene mutations.