Tracing the genomic ancestry of Peruvians reveals a major legacy of pre-Columbian ancestors.

In order to investigate the underlying genetic structure and genomic ancestry proportions of Peruvian subpopulations, we analyzed 551 human samples of 25 localities from the Andean, Amazonian, and Coastal regions of Peru with a set of 40 ancestry informative insertion-deletion polymorphisms. Using genotypes of reference populations from different continents for comparison, our analysis indicated that populations from all 25 Peruvian locations had predominantly Amerindian genetic ancestry. Among populations from the Titicaca Lake islands of Taquile, Amantani, Anapia, and Uros, and the Yanque locality from the southern Peruvian Andes, there was no significant proportion of non-autochthonous genomes, indicating that their genetic background is effectively derived from the first settlers of South America. However, the Andean populations from San Marcos, Cajamarca, Characato and Chogo, and coastal populations from Lambayeque and Lima displayed a low but significant European ancestry proportion. Furthermore, Amazonian localities of Pucallpa, Lamas, Chachapoyas, and Andean localities of Ayacucho and Huancayo displayed intermediate levels of non-autochthonous ancestry, mostly from Europe. These results are in close agreement with the documented history of post-Columbian immigrations in Peru and with several reports suggesting a larger effective size of indigenous inhabitants during the formation of the current country's population.

Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle glaucoma population.

PURPOSE: The aim of this study was to characterize a representative sample of the Peruvian population suffering open-angle glaucoma (OAG) with respect to the myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future glaucoma risk assessment. METHODS: DNA samples from 414 unrelated Peruvian subjects, including 205 open-angle glaucoma cases (10 juvenile glaucoma [JOAG], 19 normal-tension glaucoma [NTG], and 176 POAG) and 209 randomly sampled controls, were screened for nucleotide changes in MYOC exon 3 by conformational sensitive gel electrophoresis (CSGE) and mutation screening. RESULTS: We identified a probable causative novel MYOC missense mutation, Gly326Ser, in one POAG case and found a consistent genotype-phenotype correlation in eight of his relatives. We also found the known causative MYOC mutation Trp286Arg in one JOAG case and one POAG case. A known causative single base MYOC deletion, T1357, was found in one POAG case. Two previously reported silent polymorphisms, Thr325Thr and Tyr347Tyr, were found in both the case and the control populations. A novel missense variant, Met476Arg, was identified in two unrelated controls. CONCLUSIONS: The screening of exon 3 of MYOC in a representative sample of 205 independent POAG patients from Peru and 209 matched controls identified novel and previously reported mutations (both pathogenic and nonpathogenic) from other global regions. These results reflect the complex admixture of Amerindian and Old World ancestry in urban populations of Latin America, in general, and in Peru, in particular. It will be important to gather information about the ancestral origin of MYOC and other POAG gene mutations to develop screening panels and risk assessment for POAG in Peru.

Estudio genético-molecular de glaucoma primario de ángulo abierto en una familia peruana sugiere nuevo locus para glaucoma / Molecular genetic study of primary open-angle glaucoma in a Peruvian family suggests new locus for glaucoma

La contribución de la genética molecular al estudio de enfermedades hereditarias es innegable. Existen numerosos reportes de genes responsables de enfermedades hereditarios que facilitan al diagnóstico, pronóstico y también la posibilidad de terapias cuando se conoce el defecto molecular involucrado. Además, hay cientos de enfermedades en donde la identificación del defecto molecular está cerca porque se han localizado regiones cromosómicas específicas en donde se sabe, residen genes responsables de estas enfermedades. Una estrategia es precisamente, refinar paulatinamente esta ubicación a fin de caracterizar el defecto molecular, todo ello con miras a establecer posibles tratamientos. El glaucoma primario de ángulo abierto (GPAA) es una enfermedad hereditaria que puede llevar a la ceguera si no hay un diagnóstico temprano y tratamiento. Hasta ahora, se conocen seis genes que son responsables de la enfermedad y nuestro grupo está trabajando en la caracterización genético-molecular de GPAA en familias peruana usando marcadores microsatélites a fin de caracterizar su asociación con los seis grupos de marcadores. Reportamos el hallazgo de una familia peruana afectada con GPAA que no segrega con ninguno de los marcadores microsatélites de las diferentes regiones cromosómicas que se sabe están asociadas con la enfermedad. Esto apunto a la existencia de un nuevo locus responsable del GPAA en esta familia.

Molecular genetic studies are increasingly important for the study of heredity diseases and its contribution is well known. There are several hundred reports of genes responsible of genetic diseases that help in diagnosis, prognosis and possible treatment when the molecular defect is known. Primary open-angle glaucoma (POAG) is a hereditary disease that can lead to blindness if untreated. There are six known loci that can cause it and or group is working on the characterization of Peruvian families using microsatellite markers located on regions known to harbor glaucoma genes. We found a Peruvian family that does not segregate with any of the markers located near known glaucoma loci. This would account for a new locus responsible for the disease in this family.