Mexicans are a recent admixture of Amerindians, Europeans, and Africans. We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP, and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the genome, which is the hallmark of recent selection for admixed samples. The estimated selection coefficients are 0.05 and 0.07 for two datasets, which put our finding among the strongest known selections observed in humans, namely, lactase selection in northern Europeans and sickle-cell trait in Africans. Using inaccurate Amerindian training samples was a major concern for the credibility of previously reported selection signals in Latinos. Taking advantage of the flexibility of our statistical model, we devised a model fitting technique that can learn Amerindian ancestral haplotype from the admixed samples, which allows us to infer local ancestries for Mexicans using only European and African training samples. The strong selection signal at the MHC remains without Amerindian training samples. Finally, we note that medical history studies suggest such a strong selection at MHC is plausible in Mexicans. Author Summary Whether or not there exists recent selection since admixture in Latinos has been a subject of debate. To detect selection signal, a method uniquely applicable to recently admixed samples is local ancestry analysis. We infer local ancestry of admixed samples (in our study, Mexicans), and look for regions where the average ancestry of one ancestry component significantly deviates from its genome-wide average. Inferring local ancestry requires training samples that represent the genuine ancestral source populations. One major concern for previously detected selection signals in Latinos via local ancestry analysis is the inaccuracy of Amerindian training samples. This is partly due to large genetic differences among Amerindian tribes and partly due to the difficulty in obtaining Amerindian training samples. We developed a new method which allows us to learn Amerindian ancestral haplotypes from Mexican cohorts in the absence of Amerindian training samples. Our work demonstrates the existence of recent strong selection at MHC in Mexicans.
【초록키워드】 Genome, Local, Cohort, Region, humans, African, Genome-wide association study, statistical model, MHC, Haplotype, flexibility, Analysis, the strongest, medical history, Latino, subject, average, difficulty, Europeans, credibility, coefficient, debate, allele, hallmark, datasets, admixture, dbGaP, inaccuracy, Mexicans, populations, European, performed, detect, significantly, reported, absence, Taking, deviate, genetic difference, Mexican, 【제목키워드】 Selection, MHC, Strong, Mexican,