The genetic basis of population-specific differences in human skin color is a fascinating, socially relevant, and enduring mystery of human biology. For Europeans, we now know about two genes that together account for much of their lighter skin color as compared with Africans, and other genes that affect intra-population variation in skin, eye and hair color. However, the genes responsible for the lighter skin color of East Asians and Amerindians (as compared with West Africans) remain unknown. To map those genes, we searched for populations admixed for either East Asian or Amerindian ancestry and a darker-skinned ancestry. The only populations with such an admixture that also lack significant European admixture that would confound our analysis were two indigenous populations, the Orang Asli of Malaysia and the Kalinago of Dominica. Both groups exhibit large variation in skin pigmentation. The Orang Asli of Peninsular Malaysia consist of three tribes, Senoi, Proto-Malay, and Negrito, who have a complex ancestry. The Kalinago have primarily Amerindian and West African ancestry. DNA samples and skin reflectance measurements were collected from a total of >1000 individuals. Skin pigmentation, expressed as Melanin Index, ranged from 20 to 80 units, averaging 45.5 and 45.8 for the Senoi and Kalinago, respectively (as compared with 25 and 21 for East Asian and European and 55, and 56 for Negrito and West African, respectively). Samples containing European SLC24A5A111T or SLC45A2L374F alleles will be excluded from our downstream analysis to minimize interference with East Asian and Amerindian pigmentation alleles. For the same reason, we identified and are excluding individuals with an OCA2 albinism allele found in the Kalinago population. SNP genotyping of subsamples of 92 Kalinago and 78 Orang Asli samples revealed that the Negritos are distinct, that the six Senoi tribes show significant diversity, and that a highland Senoi subtribe is distinct from the rest of the Senoi. Analysis of a Kalinago subsample showed 61% Amerindian, 31% African, and 8% European ancestry, which is considerably higher Amerindian ancestry than has been reported for other Caribbean populations. Progress will be reported towards screening of whole-genome sequences from phenotypic extremes from these samples for polymorphisms that are nearly fixed in East Asians but nearly absent in Africans. CRISPR-mediated zebrafish knockouts, morphants, and RNA rescue are being used to validate candidate genes.