Origen parental, estado de no disyunción y recombinación meiótica del cromosoma 21 extra en el síndrome de Down: estudio en una muestra de población colombiana

Abstract

Introduction. Free trisomy 21 is responsible for 95% of Down syndrome cases. Advanced maternal age and susceptible recombination patterns are recognized risk factors associated to Down syndrome. Maternal origin of trisomy occurs in approximately 90% of cases; paternal and mitotic origin share the remaining 10%. However, the recombination events that serve as a risk factors for trisomy 21 have not been carefully characterized. Objective. To analyze and validate observations in a sample of Colombian trysonomy 21 cases. Materials and methods. Twenty-two Colombian families were selected, each with one affected Down syndrome (free trisomy 21) child. Microsatellite polymorphisms were used as DNA markers to determine the parental/stage origin of non-disjunction and recombination events. Nonparametric tests were used to compare our results with those reported. Multiple correspondence analysis was used to outline different groups and their associations. Results. Distribution of trisomy 21 was 90.9% maternal, 4.5% paternal and 4.5% from mitotic origin, similar to distributions reported previously. However, we found differences in the frequency of maternal meiotic stage errors between the present study (46.1% meiosis I and 53.9% meiosis II) compared to those reported previously (70% meiosis I and 30% meiosis II). Multiple correspondence analyses showed association of either local recombination events or absence of recombination with specific non-disjunction stages. Conclusions. Recombination patterns found in this study support the hypothesis that susceptible chiasmate configurations are associated to maternal meiosis I and meiosis II errors. Nondisjunction frequencies between maternal meiotic stages need to be clarified in our population.Key words: Down syndrome; nondisjunction, genetic; trisomy; meiosis; recombination, genetic; microsatellite repeats.Origen parental, estado de no disyunción y recombinación meiótica del cromosoma 21 extra en el síndrome de Down: estudio en una muestra de población colombiana Introducción. La trisomía 21 libre es responsable del 95% de los casos de síndrome de Down. La edad materna y la recombinación son los principales factores de riesgo asociados con la concepción de estos individuos. El origen materno de la trisomía ocurre en el 90% de los casos, mientras que los casos de origen paterno y mitótico comparten un 10%. Por otra parte, la recombinación como factor de riesgo para la trisomía 21 no ha sido comprobada completamente. Objetivo. Analizar y validar estas observaciones en una muestra colombiana de casos con trisomía 21 libre. Materiales y métodos. Se estudiaron 22 afectados con síndrome de Down (trisomía libre) y sus respectivos padres. Se usaron marcadores microsatélites de ADN para determinar el origen en los progenitores, el estado de no disyunción y los eventos de recombinación. Por COMUNICACIÓN BREVE 142 Biomédica 2007;27:141-8 Ramírez NJ, Belalcazar HM, Yunis JJ et al medio de pruebas no paramétricas se compararon los resultados con los reportados en la literatura. Se re...

19-base pair deletion polymorphism of the dihydrofolate reductase (DHFR) gene: maternal risk of Down syndrome and folate metabolism

“…Down syndrome (DS) is a genetic disease characterized, in most cases, by free trisomy of chromosome 21 caused by non-disjunction in maternal meiosis. 1 , 2 James et al 3 were the first to observe an increased risk of chromosome non-disjunction due to abnormal folate metabolism, and this is responsible for abnormalities in the pattern of deoxyribonucleic acid (DNA) methylation.…”