Whole genome sequencing of 1427 Mexican individuals from the oriGen cohort

Latin American populations remain underrepresented in genomic research. To help address this, we present an analysis of high-coverage whole-genome data from 1481 volunteers recruited as part of the oriGen Project. We identify over 47.2 million SNVs and 8.1 million short indels, including nearly 3 million non-singleton short variants absent from dbSNP and the Mexico City Prospective Study. Admixture analysis indicates that a Mexican training dataset is needed to more accurately estimate ancestry compositions by genetic similarity. Analysis of copy number variation associated with MX-AMR highlights several loci, including LCE1D and RHD. Interestingly, while 3.1% of participants carry homozygous deletions in the RHD gene, which determines the Rh blood group, this frequency dropped to 0.6% among individuals with high MX-AMR. Since the RHD deletion is rare in East Asians, and the Rh-negative phenotype is rare in Indigenous American populations, our results support the hypothesis that the Rh-negative blood group increased in frequency during the Spanish conquest rather than by genetic drift. We also find that 10% of volunteers are heterozygotes for the 22-42128945-C-T Loss of Function variant in CYP2D6, an enzyme involved in metabolizing painkillers, and tamoxifen. This work helps address the underrepresentation of Mexican populations in genomic research. Mexican populations remain underrepresented in genomics. Here, Aguilar-Ordoñez et al. report on 1,481 whole-genomes from the oriGen project, identifying key variants like a CNV driving the Rh-negative blood group.