Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Par 3/genética , Hibridização in Situ Fluorescente , Southern Blotting , Bandeamento Cromossômico , DNA Complementar/genética , Humanos , Células Híbridas/metabolismo , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo , Reação em Cadeia da PolimeraseRESUMO
Cytogenetic and fluorescence in situ hybridization studies have shown the presence of telomeric repeats in translocation present in three patients with hematopoietic malignancies. One had jumping translocations, involving 1q12 and 2q, 16p, and 19q. These sequences were detected by FISH only in derivative chromosomes t(1;16) and t(1;19) in the first patient, and t(1;7) in the second. They were not seen in derivative t(1;2) and t(7;8), respectively. Interstitial telomeric sequences were observed in der(2)t(1;2) in about half of the metaphases in the third patient. The instability of interstitial telomeric DNA repeats in translocations is shown by the present findings. Moreover it supports the hypothesis that the presence of interstitial telomere repeats is not sufficient to make it functional.
Assuntos
Neoplasias Hematológicas/genética , Telômero/genética , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 2 , Feminino , Humanos , Cariotipagem , Masculino , Sequências Repetitivas de Ácido Nucleico/genéticaRESUMO
Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that predisposes to nervous system tumors. The schwannomin (also termed merlin) protein encoded by the NF2 gene shows a close relationship to the family of cytoskeleton-to-membrane proteins linkers ERM (ezrin-radixin-moesin proteins). Even though penetrance of the disease is >95% and no genetic heterogeneity has been described, point mutations in the NF2 gene have been observed in only 34-66% of the screened NF2 patients, depending on the series. In order to generate tools that would enable an exhaustive alteration screening for the NF2 gene, we have deduced its entire genomic sequence. This knowledge has provided the delineation of a mutation screening strategy which, when applied to a series of 19 NF2 patients, has revealed a high recurrence of large deletions in the gene and has raised the efficiency of mutation detection in NF2 patients to 84% of the cases in this series. The remaining three patients who express two functional NF2 alleles are all sporadic cases, an observation compatible with the presence of mosaicism for NF2 mutation.
Assuntos
Genes da Neurofibromatose 2/genética , Neurofibromatose 2/genética , Células Cultivadas , DNA/química , DNA/genética , Éxons , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Mutação Puntual , Polimorfismo Genético , RNA/análise , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Balanced chromosomal abnormalities such as translocations and inversions have been identified in many genetic diseases. Cloning of the breakpoints involved in these abnormalities has led to the identification of the disease-related genes. Recent reports suggest the presence of a mental retardation locus at Xq11-12. We have identified a female patient with a balanced translocation t (X;12) (q11;q15) associated with mild mental retardation. We identified a yeast artificial chromosome spanning the X-chromosome breakpoint by using fluorescent in situ hybridization techniques. A cosmid library of this YAC has been constructed and the search for candidate genes is in progress.
Assuntos
Cromossomos Humanos Par 12 , Deficiência Intelectual/genética , Translocação Genética/genética , Cromossomo X , Criança , Bandeamento Cromossômico , Quebra Cromossômica , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura , Cromossomos Humanos Par 12/genética , Cosmídeos , Sondas de DNA , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Cromossomo X/genéticaRESUMO
Fluorescence in situ hybridization (FISH) to interphase nuclei was performed to order probes corresponding to bands 11q22-q23 where the ataxia-telangiectasia (AT) gene(s) have been located. Cosmid probes and one phage probe previously localized to this chromosome 11 region by FISH to metaphase chromosomes, were hybridized to interphase nuclei of the somatic cell hybrid J1a, which contains chromosome 11 as the only human chromosome. Two-color FISH was used with a centromeric reference probe marker. The following order was obtained: cen-D11S385 (CJ52.75)-CJ52.3-D11S384 (CJ52.193)-CJ52.114-D11S424 (CJ52.77)-D11S132-NCAM-D11S351 (CJ52.208)-tel. The validity of using the centromeric probe was illustrated by showing that a probe corresponding to 11p13 hybridized more closely to the centromere than a probe corresponding to 11q22-q23, and by using cosmids hybridized three by three.
Assuntos
Ataxia Telangiectasia/genética , Cromossomos Humanos Par 11 , Hibridização in Situ Fluorescente/métodos , Núcleo Celular , Mapeamento Cromossômico , Cosmídeos , Sondas de DNA , Corantes Fluorescentes , Ligação Genética , Marcadores Genéticos , Humanos , Células Híbridas , Interfase/genética , Masculino , Metáfase/genética , Reação em Cadeia da PolimeraseRESUMO
An Alu polymerase chain reaction (PCR) probe specific for chromosome 11 prepared from the somatic cell hybrid J1 was used to analyze karyotypes of eight patients with acute monocytic leukemia (AML-M5). Chromosome painting confirmed the t(9;11) in one patient and a der(1)t(1;6)t(6;11) in another and allowed the identification of a complex rearrangement involving chromosomes 9, 11, and 17, previously classified as del(11)(q23), in a third patient. An analysis of five patients with AML-M5 and a normal karyotype did not detect abnormalities of chromosome 11. The usefulness of chromosome painting combined with in situ hybridization with probes previously located on particular chromosomes is emphasized.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 11/ultraestrutura , Hibridização in Situ Fluorescente , Leucemia Monocítica Aguda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Deleção Cromossômica , Cromossomos Humanos Par 17/ultraestrutura , Cromossomos Humanos Par 9/ultraestrutura , Sondas de DNA , Feminino , Humanos , Lactente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Translocação GenéticaRESUMO
Thirteen cosmid probes were mapped on the long arm of chromosome 11 between 11q22 and 11q24 by nonradioactive in situ hybridization. Starting with these localizations and those of other probes mapped to 11q23, four acute leukemias with translocations involving 11q23 were studied with the same method. The translocation breakpoints of the t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p21-p22;q23), and t(11;19)(q23;p13) were confirmed to be distal to CD3D. The probe cC111-304 was proximal to the t(11;19) breakpoint while distal to the breakpoints of the other rearrangements. In view of the diversity of chromosomal abnormalities involving band 11q23, our finding extends the molecular heterogeneity of the breakpoint localization in leukemias with rearrangements involving 11q23.
Assuntos
Cromossomos Humanos Par 11 , Leucemia Monocítica Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adolescente , Criança , Pré-Escolar , Mapeamento Cromossômico , Sondas de DNA , Feminino , Corantes Fluorescentes , Rearranjo Gênico , Humanos , Cariotipagem , Hibridização de Ácido NucleicoRESUMO
The enzymatic activities of gamma-glutamyl-transpeptidase and of aminopeptidase M have been determined in amniotic fluids taken in pregnancies with a trisomic conceptus. The low values obtained in these fluids may be the consequence of fetal growth retardation.
Assuntos
Aminopeptidases/metabolismo , Líquido Amniótico/enzimologia , Aberrações Cromossômicas/enzimologia , gama-Glutamiltransferase/metabolismo , Fosfatase Alcalina/metabolismo , Antígenos CD13 , Transtornos Cromossômicos , Cromossomos Humanos 13-15 , Cromossomos Humanos 16-18 , Síndrome de Down/enzimologia , Humanos , Monossomia , Aberrações dos Cromossomos Sexuais/enzimologia , TrissomiaRESUMO
Spontaneous and mitomycin C(MMC)-induced sister chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify whether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.
Assuntos
Troca Genética , Retinoblastoma/genética , Troca de Cromátide Irmã , Células Cultivadas , Pré-Escolar , Cromátides/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Linfócitos/ultraestrutura , Masculino , Mitomicinas/farmacologia , Pele/ultraestrutura , Fatores de TempoRESUMO
A series of 226 antenatal diagnoses of chromosome structural re-arrangements in 181 couples has shown the usefulness of such diagnosis for couples including a genitor carrying a balanced anomaly. Analysis of the data has elicited major variations in the incidence of unbalanced anomalies in foetal cells and has provided information which can usefully be applied to genetic counselling.
