RESUMO
Coeliac disease (CD) is a malabsorptive disorder of the small intestine resulting from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the whole genetic susceptibility. Several regions of potential linkage on chromosomes 3q, 5q, 10q, 11q, 15q and 19q have already been reported in the literature. These six regions were analyzed with the Maximum Lod Score method on a dense set of markers. A new sample of 89 Italian sibpairs was available for study. There was no evidence for linkage for any of the regions tested, except for chromosome 5q. For this region, our data, as well as a sample of 93 sibpairs from our first genome screen (Greco et al. 1998), are compatible with the presence of a risk factor for CD with a moderate effect.
Assuntos
Doença Celíaca/genética , Cromossomos Humanos Par 5 , Doença Celíaca/etnologia , Cromossomos , Saúde da Família , Feminino , Marcadores Genéticos , Humanos , Itália , Escore Lod , Masculino , Fatores de RiscoRESUMO
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.
Assuntos
Antígenos de Diferenciação/genética , Doença Celíaca/genética , Ligação Genética , Imunoconjugados , Polimorfismo Genético , Abatacepte , Adulto , Antígenos CD , Antígeno CTLA-4 , Criança , Saúde da Família , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Itália , Masculino , TunísiaRESUMO
Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.
Assuntos
Doença Celíaca/genética , Genoma Humano , Ligação Genética , Testes Genéticos , Genótipo , HumanosRESUMO
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.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA , Repetições de Trinucleotídeos , Proteínas Adaptadoras de Transdução de Sinal , Alelos , Proteínas de Transporte , DNA/análise , Reparo do DNA/genética , Feminino , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil/genética , Variação Genética , Humanos , Masculino , Proteína 1 Homóloga a MutL , Mutação , Proteínas de Neoplasias/genética , Proteínas Nucleares , Cromossomo X/genéticaRESUMO
Linkage data for familial incontinentia pigmenti (IP2) and 17 X chromosomal markers are reported. The linkage previously found between IP2 and the F8C locus is confirmed (Z max = 11.85 at theta = 0.028). Linkage is established with distal markers DXS1108 (Z max = 10.06 at theta = 0.00) and DXYS154 (Z = 9.07 at theta = 0.019). Multipoint analysis supports the distal localization of the IP2 gene with respect to the F8C locus.
Assuntos
Genes , Incontinência Pigmentar/genética , Cromossomo X , Animais , Mapeamento Cromossômico , Anormalidades do Olho/genética , Feminino , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Camundongos , Linhagem , Especificidade da EspécieRESUMO
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.
Assuntos
Cromossomo X , Mapeamento Cromossômico , DNA Complementar/genética , Genes , Marcadores Genéticos , Humanos , Células Híbridas , Cromossomo X/efeitos da radiaçãoRESUMO
The chromosomal localization of four genes which are expressed mainly in the liver has been undertaken for the rat. Using a panel of hybrid clones segregating rat chromosomes, and Southern blot analysis, alpha 1-AT (PI), PEPCK, ADH and FDP are assigned to rat Chromosomes (Chr) 6, 3, 2 and 17, respectively. Groups of synteny among rat, mouse and human species are discussed in relationship to the new assignments.
Assuntos
Álcool Desidrogenase/genética , Mapeamento Cromossômico , Frutose-Bifosfatase/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , alfa 1-Antitripsina/genética , Animais , Clonagem Molecular , Células Híbridas , Camundongos , RatosRESUMO
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.
Assuntos
DNA de Neoplasias/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas Experimentais/genética , Fenilalanina Hidroxilase/biossíntese , Transfecção/genética , Animais , DNA de Neoplasias/isolamento & purificação , Biblioteca Genômica , Immunoblotting , Neoplasias Hepáticas Experimentais/enzimologia , Hibridização de Ácido Nucleico , Fenótipo , Fenilalanina Hidroxilase/genética , Plasmídeos/genética , RNA Mensageiro/análise , RNA Neoplásico/isolamento & purificação , Ratos , Células Tumorais CultivadasRESUMO
A panel of hybrid clones segregating rat chromosomes in a mouse background was used to determine the chromosomal localization of three genes specifically expressed in hepatocytes. The phenylalanine hydroxylase, tyrosine aminotransferase, and pyruvate kinase genes were assigned to rat chromosomes 7, 19, and 2, respectively.
Assuntos
Mapeamento Cromossômico , Fenilalanina Hidroxilase/genética , Piruvato Quinase/genética , Tirosina Transaminase/genética , Animais , Southern Blotting , RatosRESUMO
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.
Assuntos
Neoplasias Hepáticas Experimentais/metabolismo , Fosfotransferases/análise , Uridina Quinase/análise , Uridina/metabolismo , Animais , Linhagem Celular , Fosforilação , RatosAssuntos
Marcadores Genéticos , Metástase Neoplásica/fisiopatologia , Neoplasias Experimentais/imunologia , Animais , Divisão Celular , Fusão Celular , Linhagem Celular , Células Cultivadas , Humanos , Células Híbridas , Cariotipagem , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Mutação , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , FenótipoRESUMO
Partial purification of uridine--cytidine kinase (EC 2.7.1.48) from foetal rat liver by chromatography on DEAE-cellulose gives two active fractions. The first in order of elution was identified as a form specific for foetal liver. It was purified 300-fold. The second fraction was common to foetal, and adult rat liver and spleen and was purified 20-fold. The foetal fraction of the enzyme was found to be heat-sensitive and protected against inactivation by PO34- anions. The two isolated forms have different apparent Km for uridine, respectively 410 muM for the foetal form and 52 muM for the adult form.
