RESUMEN
X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.
Asunto(s)
Proteínas Portadoras/genética , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Péptidos y Proteínas de Señalización Intracelular , Trastornos Linfoproliferativos/genética , Mutación , Dominios Homologos src/genética , Antígenos CD , Linfocitos B/inmunología , Linfocitos B/virología , Proteínas Portadoras/metabolismo , Clonación Molecular , Femenino , Ligamiento Genético , Glicoproteínas/metabolismo , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Humanos , Inmunoglobulinas/metabolismo , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/virología , Masculino , Datos de Secuencia Molecular , Linaje , Receptores de Superficie Celular , Alineación de Secuencia , Eliminación de Secuencia , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Linfocitos T/inmunología , Linfocitos T/virología , Cromosoma XRESUMEN
A putative novel murine serine protease, DISP, was identified by cDNA indexing and shown to be expressed primarily in distal gut. FISH analysis showed it to be localised to mouse chromosome 17A3. A possible human homologue for DISP has been identified. DISP is a novel member of clan SA/family S1 of the serine proteases, at present of unknown function.
Asunto(s)
Intestino Delgado/enzimología , Serina Endopeptidasas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario/análisis , Electroforesis en Gel de Agar , Células Epiteliales/metabolismo , Expresión Génica , Íleon/metabolismo , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina Endopeptidasas/análisis , Serina Endopeptidasas/químicaRESUMEN
In cDNA indexing, differentially expressed genes are identified by the display of specific, corresponding subsets of cDNA. Subdivision of the cDNA population is achieved by the sequence-specific ligation of adapters to the overhangs created by class IIS restriction enzymes. However, inadequate specificity of ligation leads to redundancy between different adapter subsets. We evaluate the incidence of mismatches between adapters and class IIS restriction fragments during ligation and describe a modified set of conditions that improves ligation specificity. The improved protocol reduces redundancy between amplified cDNA subsets, which leads to a lower number of bands per lane of the differential display gel, and therefore simplifies analysis. We confirm the validity of this revised protocol by identifying five differentially expressed genes in mouse duodenum and ileum.
Asunto(s)
Clonación Molecular/métodos , ADN Complementario/análisis , ADN Complementario/genética , Animales , Northern Blotting , ADN Ligasas , Duodeno , Expresión Génica , Íleon , Ratones , Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Sensibilidad y EspecificidadRESUMEN
We present a family in which an initial clinical diagnosis of autosomal dominant pure hereditary spastic paraparesis (HSP) was made on the basis of a three generation pedigree in which both males and females presented with a spastic paraparesis. Subsequent biochemical and genetic analysis revealed that the family was in fact affected by the adrenomyeloneuropathy subtype of X-linked adrenoleukodystrophy. In the family described, both males and females were affected by a spastic paraparesis, and there was no male to male transmission, consistent with both autosomal dominant and X-linked inheritance. This report illustrates the importance of assaying very long chain fatty acids (VLCFAs) in any HSP family where there is no male to male transmission.
Asunto(s)
Adrenoleucodistrofia/diagnóstico , Adrenoleucodistrofia/genética , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genética , Adrenoleucodistrofia/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Coenzima A Ligasas/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
BACKGROUND & AIMS: Different digestive enzymes and transporters are present in the duodenum, jejunum, and ileum, but the factors determining region-specific gene expression are not yet understood. Homeobox transcription factors are important in defining gradients of cellular differentiation. The aim of this study was to investigate whether their expression differs between proximal (duodenal) and distal (ileal) regions of human small intestine. METHODS: Intestinal RNA was prepared from surgical patients, and reverse-transcription polymerase chain reactions (PCRs) performed with mixed sequence oligonucleotide primers based on conserved regions. PCR products were identified by cloning and sequencing. Transcript abundance was determined by Northern blotting. RESULTS: The human homologues were identified as Cdx-1, Cdx-2 (or Cdx-3), Pdx-1 (previously named Islet/duodenal homeobox [Idx]-1, Ipf-1, or Stf-1), and 13 human homeodomain cluster genes, including HOXB3, HOXB4, and HOXA6. The relative abundance of some of these differed between duodenum and ileum. Pdx-1 transcripts were found only in duodenum, Cdx-2, Cdx-1, and HOXB3 were readily detectable in both regions, with Cdx-1 having a more marked distal expression. CONCLUSIONS: Many homeobox genes are expressed in human adult small intestinal mucosa, and some are found predominantly in one region.