RESUMEN
We investigated complex genomic rearrangements (CGRs) consisting of triplication copy-number variants (CNVs) that were accompanied by extended regions of copy-number-neutral absence of heterozygosity (AOH) in subjects with multiple congenital abnormalities. Molecular analyses provided observational evidence that in humans, post-zygotically generated CGRs can lead to regional uniparental disomy (UPD) due to template switches between homologs versus sister chromatids by using microhomology to prime DNA replication-a prediction of the replicative repair model, MMBIR. Our findings suggest that replication-based mechanisms might underlie the formation of diverse types of genomic alterations (CGRs and AOH) implicated in constitutional disorders.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Reparación del ADN/genética , Replicación del ADN/genética , Reordenamiento Génico/genética , Pérdida de Heterocigocidad/genética , Modelos Genéticos , Disomía Uniparental/genética , Secuencia de Bases , Humanos , Hibridación Fluorescente in Situ , Datos de Secuencia Molecular , Países Bajos , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADNRESUMEN
In the present study, we typed our previously reported two microsatellite markers, DXYS241 and DXYS266 together with a basic set of nine Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DXYS156Y, DYS413) on Y chromosomes from two Bolivian populations. Unrelated males from communities living at high- (N=59) and low- (N=142) altitude, were studied. Combining the alleles into 11 Y-STRs haplotypes revealed that the high-altitude population is significantly less diverse than the low-altitude population. Haplotype diversities of 0.927+/-0.029 and 0.996+/-0.002 were found within the high-altitude, and the low-altitude populations, respectively. Within the high-altitude population 40 haplotypes were detected, whereas in the low-altitude population 113 haplotypes were found. Only three haplotypes were shared between both populations. Haplotyping-based discrimination using the 11 Y-STRs including our new two microsatellite markers DXYS241 and DXYS266 was shown to be powerful than using the conventional 9 Y-STRs, especially for the low-altitude Bolivian population. This 11 Y-STRs-based haplotyping system shows a very high potential for discrimination and could provide an ideal tool for forensic analysis and population studies. Moreover, this study includes data about two Bolivian populations which were not previously reported, this will help in building a world-wide database for future use in forensic and legal studies.