RESUMEN
Mental retardation is a very common and extremely heterogeneous disorder that affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoints in Xp11, viz., t(X;17)(p11;p13) and t(X;20)(p11;q13). (Fiber-) FISH analysis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, separated by approximately 8 Mb. High-resolution mapping of the X- chromosome breakpoints using Southern blot hybridization resulted in the isolation of breakpoint-spanning genomic subclones of 3 kb and 0. 5 kb. The Xp11.4 breakpoint is contained within a single copy sequence, whereas the Xp11.23 breakpoint sequence resembles an L1 repetitive element. Several expressed sequences map close to the breakpoints, but none was found to be inactivated. Therefore, mechanisms other than disruption of X-chromosome genes likely cause the phenotypes.
Asunto(s)
Rotura Cromosómica/genética , Discapacidad Intelectual/genética , Translocación Genética/genética , Cromosoma X/genética , Adolescente , Adulto , Niño , Preescolar , Clonación Molecular , Compensación de Dosificación (Genética) , Exones/genética , Etiquetas de Secuencia Expresada , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Mapeo Físico de Cromosoma , ARN Mensajero/análisis , ARN Mensajero/genética , Recombinación Genética/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Lugares Marcados de SecuenciaRESUMEN
Fluorescence in situ hybridization (FISH) has been used to visualize the spatial orientation of homologous chromosome regions in interphase nuclei of exponentially growing mouse fibroblasts. Simultaneous labeling of replicating DNA with the halogenated base analog 5-bromodeoxyuridine (BrdU) shows preferential somatic pairing of the imprinted region on distal mouse chromosome 7 during the S phase of the cell cycle. Trans-interactions between oppositely imprinted chromosome regions may be important for the maintenance of imprinting.