ABSTRACT
RESUMEN El labio y paladar hendido es una de las patologías congénitas con mayor prevalencia en el mundo. En el presente trabajo se hace un análisis de 12 PNU localizados en las secuencias genómicas de ABCA4, BMP4, MSX1, SUMO1, VAX1 y IRF6, bajo una perspectiva epidemiológica, de genética molecular, genómica y de genética de poblaciones; todo lo anterior aplicado a una población de Querétaro, México, de origen genético mixto. Material y métodos: Se realizó un estudio observacional, analítico y descriptivo a partir de muestras de 93 tríadas (sujetos de estudio y sus padres). Al seleccionar PNU que puedan ser diferenciados por medio de RFLP esperamos distinguir entre marcadores genéticos que: 1) cumplan con la ecuación de equilibrio de Hardy-Weinberg y 2) validarlos como potenciales marcadores genéticos para ser empleados en estudios de asociación en poblaciones cerradas de origen genético mixto con labio y paladar hendido (Amealco, Querétaro, México). De ser así, posteriormente se plantea probar las frecuencias obtenidas con una población seleccionada genéticamente cerrada de Amealco, Querétaro. Resultados: Después de realizar el análisis RFLP de 12 PNU localizados en la secuencia de genes ABCA4, BMP4, MSX1, SUMO1, VAX1 y IRF6, hallamos el mismo alelo para PNU analizado, el cual se encuentra en el 100% de la población. Conclusión: De los 12 PNU analizados, en este reporte, por primera vez se menciona la frecuencia de cinco de ellos. Los restantes siete presentaron la misma frecuencia reportada en la literatura. Aunque los PNU seleccionados no fueron de utilidad como marcadores genéticos debido a que el mismo alelo está presente en el 100% de la población general. El hecho de haberlos encontrado en el mismo genotipo de todas las muestras indica que la población de la ciudad de Querétaro es genéticamente cerrada y con base en esto extremadamente útil para futuras validaciones de otros PNU como posibles marcadores genéticos.
ABSTRACT The cleft lip and palate is one of the congenital pathologies with greater prevalence in the world. In the present work, there is an analysis of 12 SNP's located in genomic sequences of ABCA4, BMP4, MSX1, SUMO1, VAX1 andIRF6, under an epidemiological perspective, molecular genetics, genomics and population genetics. All of the above applied to a population of Queretaro, Mexico, of mixed genetic origin. Material and methods: A study was conducted of observation, analytic and descriptive study with samples from 93 triads (study subjects and their parents). When you select SNP's that can be differentiated by RFLP (Restriction Fragment Length Polymorphism)we hope to distinguish between genetic markers that: 1)comply with the equation of balance of Hardy-Weiner and 2) Validate them as potential genetic markers to be used in studies of association in closed populations of genetic origin mixed with cleft lip and palate in Amealco, Queretaro, Mexico. If so subsequently raises test the frequencies obtained with a selected population genetically closed in Amealco, Queretaro. Results: After performing the RFLP analysis of 12 SNP's located in the sequence of genes ABCA4, BMP4, MSX1, SUMO1, VAX1 and IRF6, we find the same allele for SNP analyzed which is located in the 100% of the population. Conclusion: Of the 12 SNP's analyzed in this report, for the fi rst time 5 of them are mentioned their frequency. The rest of them had the same frequency reported in the literature. Although the SNP's selected were not useful as a genetic markers due to the same allele is present in 100% of the general population. The fact of having found in the same genotype of all samples indicates that the population of the city of Queretaro is genetically closed and on the basis of this extremely useful for future validations of other SNP's as potential genetic markers.
ABSTRACT
Introduction@#Base excision repair (BER) is mainly responsible for the correction of small base changes of DNA damage. BER pathway involved many enzymes including OGG1 and XRCC1. The defective DNA repair is associated with an increased risk of various cancers including hematologic malignancies-leukemia and myelodysplastic syndrome (MDS). However, it is deniably these polymorphisms alter the susceptibility and clinical outcome of MDS patients.@*The aim@#This study was to evaluate the impact of polymorphisms in gene encoding one protein of BER system: XRCC1 Arg399Gln in MDS and healthy population.@*Methods@#In this study, we recruited 60 health control group [median 47.9 years, 9 MDS subjects [median 56.6 years] were included in this study. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Allele and genotype frequencies were calculated by direct counting.@*Result@#The frequencies of genotypes of XRCC1 Arg399Gln were as follows: Arg /Arg 1 (11%), Arg/Gln 6 (66%), Gln/Gln 2 (22%) in MDS and Arg /Arg 18.4%, Arg/Gln40%, Gln/Gln41.6% in health control for XRCC1 Arg399Gln. The result revealed that genotypes Arg399Gln increased the risk of MDS@*In conclusion@#this study is the first to analyze XRCC1 SNPs and their associated risk of MDS in Mongolian samples. To fully understand the role of DNA damage and DNA repair in the MDS, prospective studies are needed and other genes (OGG1 Ser326Cys, MUTYH Gln324His, APE Asp148Glu) of base excision repair pathway should be analyzed.