Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample.Author Summary: Cuba is the largest island of the Greater Antilles and its most populous country. The post-Columbian history of the Caribbean has been marked by the encounter of people from different continents. Here, we present an admixture analysis of 1,019 individuals from all the provinces of Cuba, using autosomal, mtDNA and Y-chromosome markers. We also analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation (melanin index). The highest proportions of African ancestry were observed in the Southeastern provinces of Santiago de Cuba and Guantánamo, and the highest proportions of Native American ancestry were found in the Eastern provinces of Granma, Holguín and Las Tunas. Similar geographic patterns were observed in the analyses of the uniparental markers. Additionally, by comparing the autosomal and uniparental admixture proportions, we identified a clear sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side than the maternal side, and conversely higher Native American and African contributions from the maternal side than the paternal side. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 show a strong association with skin pigmentation in the sample.