RESUMO
The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.
Assuntos
Sequenciamento do Exoma , Genoma Humano , Genótipo , Hispânico ou Latino , Adulto , Humanos , África/etnologia , América/etnologia , Europa (Continente)/etnologia , Frequência do Gene/genética , Genética Populacional , Genoma Humano/genética , Técnicas de Genotipagem , Hispânico ou Latino/genética , Homozigoto , Mutação com Perda de Função/genética , México , Estudos ProspectivosRESUMO
Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiple autoantigens as targets,resulting in damage to many organs of the body. The disease is more common in females (> 90%) and around 15% of the cases present during childhood.Systemic lupus erythematosus is a complex disease in which both genetic (susceptibility/protection alleles) and environmental factors (infections, drugs, stress, etc.) contribute to its development.The current knowledge on genetic factors involved in SLE is based on the results of linkage analyses in multi-case families as well as from case-control or family-based genetic association studies. These types of genetic analyses have contributed to identifying susceptibility genes and constitute the first step towards understanding the molecular mechanisms underlying SLE.The aim of this review is to provide a current picture of the genes identified as susceptibility factors for SLE, and to highlight the ones described in the Mexican population.