RESUMEN
Coeliac disease (CD) is a multifactorial disease for which there is an intensive search for genetic risk factors. Some authors found an association between the CTLA-4 region and CD. In the present work, we investigate the possible implication of the CTLA-4 region as a genetic risk factor for CD, through two statistical approaches: the maximum likelihood score (MLS) test in a large Italian sample of affected sib-pairs using polymorphic genetic markers on chromosome 2, and the transmission disequilibrium test (TDT) in continental Italian and Tunisian families using the CTLA-4 exon 1 49 A/G polymorphism. None of these approaches provides evidence for linkage or association between the CTLA-4 region and CD. This might result from a difference in the CTLA-4 region from population to population, either in its involvement as a risk factor or in the strength of linkage disequilibrium.
Asunto(s)
Antígenos de Diferenciación/genética , Enfermedad Celíaca/genética , Ligamiento Genético , Inmunoconjugados , Polimorfismo Genético , Abatacept , Adulto , Antígenos CD , Antígeno CTLA-4 , Niño , Salud de la Familia , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , TúnezRESUMEN
The allelic variation of the FMR1 CGG repeat was investigated by small-pool PCR in nonneoplastic peripheral blood leukocytes from HNPCC patients and matched controls for similar CGG repeat lengths. The allelic variation for repeat lengths appears to be roughly twice as frequent in HNPCC patients as in controls, especially when patients are mutated in hMLH1. There are more expansions in HNPCC patients (42%) than in controls (20%) but this difference is statistically borderline. The mean length of expansions relative to the genuine size did not differ in HNPCC patients or controls (respectively 17% and 20% of the constitutional allelic length). The reported data suggest that instability within nonneoplastic cells of a subset of HNPCC patients might be one mechanism for transition from normal to the premutation range of the FMR1 CGG repeat.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN , Repeticiones de Trinucleótidos , Proteínas Adaptadoras Transductoras de Señales , Alelos , Proteínas Portadoras , ADN/análisis , Reparación del ADN/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil/genética , Variación Genética , Humanos , Masculino , Homólogo 1 de la Proteína MutL , Mutación , Proteínas de Neoplasias/genética , Proteínas Nucleares , Cromosoma X/genéticaRESUMEN
Two genes (QM and biglycan), three cDNAs expressed in the brain (TH4, TH27, p877) and two microsatellites (AFM224zg11 and AFM287ze5) are assigned in the six sub regions delimited by an IRHs panel of the human Xq28 region.
Asunto(s)
Cromosoma X , Mapeo Cromosómico , ADN Complementario/genética , Genes , Marcadores Genéticos , Humanos , Células Híbridas , Cromosoma X/efectos de la radiaciónRESUMEN
Genomic DNA from cells producing the liver-specific enzyme phenylalanine hydroxylase (PAH) should contain, in active form, genes encoding regulators of PAH expression. We have transfected genomic DNA from PAH-producing rat hepatoma cells to PAH-deficient mouse hepatoma cells, and selected in tyrosine-deficient medium for cells producing the enzyme. The frequency of colonies obtained was similar to that for transfer of a single-copy gene. Genomic DNA from the primary transfectants permitted the isolation in tyrosine-free medium of secondary transfectants. Control experiments, using donor DNA from PAH-negative rat or mouse hepatoma cells also permitted the isolation of PAH-expressing cells, but at a frequency 10-30 times lower. The transfectants isolated in tyrosine-deficient selective medium all produced PAH mRNA. This transcript was from the previously silent mouse gene, which had not undergone amplification or gross rearrangement. Most of the transfectants contained less than 0.1% rat DNA. A search for other functions that might have been simultaneously activated was negative. It is concluded that the mouse transfectants acquired from the PAH+ rat donor some sequences whose presence permits activity of the previously silent PAH gene.
Asunto(s)
ADN de Neoplasias/genética , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Hepáticas Experimentales/genética , Fenilalanina Hidroxilasa/biosíntesis , Transfección/genética , Animales , ADN de Neoplasias/aislamiento & purificación , Biblioteca Genómica , Immunoblotting , Neoplasias Hepáticas Experimentales/enzimología , Hibridación de Ácido Nucleico , Fenotipo , Fenilalanina Hidroxilasa/genética , Plásmidos/genética , ARN Mensajero/análisis , ARN Neoplásico/aislamiento & purificación , Ratas , Células Tumorales CultivadasRESUMEN
In a family of clonal lines derived from the Reuber H 35 rat hepatoma, four electrophoretically distinct molecular forms of uridine kinase (UK I, II, III, and IV) have been characterized. They are the same as those found in foetal rat liver. Different UK profiles occur in these cell lines, and no strict correlation could be established between the state of differentiation of the cells and the form of UK expressed. A clone of somatic hybrid cells between line p4 (form 1 only) and Fu5-5 (forms II, III, and IV) that does not express form I indicates that p4 cells may lack a factor controlling the polymerization of form I. This variety of clonal cell lines was used to study the uptake and phosphorylation of labeled uridine. The results suggest a relationship between the UK form present and the rate uridine phosphorylation by the intact cells.