RESUMO
Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).
Assuntos
Genes Supressores de Tumor/genética , Predisposição Genética para Doença/genética , Neoplasias Primárias Múltiplas/genética , Proteínas/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor , Sequência de Aminoácidos , Domínio Catalítico , Cromossomos Humanos Par 16/genética , Clonagem Molecular , Mapeamento de Sequências Contíguas , Enzima Desubiquitinante CYLD , Éxons/genética , Feminino , Genes Dominantes/genética , Mutação em Linhagem Germinativa/genética , Humanos , Perda de Heterozigosidade/genética , Masculino , Dados de Sequência Molecular , Mutação/genética , Neoplasias Primárias Múltiplas/patologia , Polimorfismo Genético/genética , Proteínas/química , RNA Mensageiro/análise , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos , Sitios de Sequências Rotuladas , Neoplasias Cutâneas/patologia , Tioléster Hidrolases/química , Ubiquitina TiolesteraseRESUMO
Germ-line mutations in the LKB1 gene on chromosome 19p are responsible for most cases of the Peutz-Jeghers syndrome, in which intestinal hamartomas are associated with elevated risks of several cancer types, including breast cancer. We have evaluated the role of somatic mutations in LKB1 in breast cancer. Of 40 informative primary breast cancers, 3 showed loss of heterozygosity on chromosome 19p in the vicinity of LKB1, and no somatic mutations of LKB1 were observed in 62 primary breast cancers and 17 established breast cancer cell lines. The results indicate that mutations in LKB1 do not play an important role in the development of sporadic breast cancer.
Assuntos
Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Cromossomos Humanos Par 19 , DNA de Neoplasias/genética , Feminino , Humanos , Perda de Heterozigosidade , Síndrome de Peutz-Jeghers/enzimologia , Células Tumorais CultivadasRESUMO
Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 14/genética , Bócio Nodular/genética , Neoplasias da Glândula Tireoide/genética , Canadá , Feminino , Ligação Genética/genética , Marcadores Genéticos , Haplótipos/genética , Humanos , Escore Lod , Masculino , Linhagem , Receptores da Tireotropina/genética , Neoplasias da Glândula Tireoide/etiologiaRESUMO
The genome of the amylolytic yeast strain Lipomyces starkeyi NCYC 1436 was analysed using contour-clamped homogeneous electric field gel electrophoresis (CHEF). The banding pattern under a variety of running conditions indicating the presence of 11 different chromosome-sized DNA molecules. The sizes of these chromosome bands were determined by comparison with chromosomes from standard strains of Schizosaccharomyces pombe and Saccharomyces cerevisiae. The chromosomal bands were estimated to be within the range 0.7-2.8 Mb, with the genome (excluding mitochondrial DNA) estimated at 15 Mb. The molecular cloning of the TRP1 gene, isolated from a genomic library of this strain, is also reported: the gene was present on a 6.5-kb Sau3A DNA fragment, and complemented the trpC gene of E. coli. The DNA sequence was determined (EMBL accession No. Z68292) and compared to other tryptophan biosynthetic genes encoding N-(5'-phosphoribosyl) anthranilate isomerase (PRAI) activity. The gene was also used as a probe in hybridization studies, and by this means, its chromosomal location was identified.
Assuntos
Aldose-Cetose Isomerases , Proteínas Fúngicas/genética , Genes Fúngicos , Proteínas de Saccharomyces cerevisiae , Saccharomycetales/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , DNA Fúngico/genética , DNA Fúngico/isolamento & purificação , Eletroforese em Gel de Campo Pulsado , Cariotipagem , Dados de Sequência Molecular , TATA BoxAssuntos
Bancos de Espécimes Biológicos , DNA Fúngico , DNA Recombinante , Biblioteca Gênica , Vetores Genéticos/genética , Genoma Fúngico , Micologia/métodos , Leveduras/genética , Clonagem Molecular , Enzimas de Restrição do DNA , DNA Fúngico/isolamento & purificação , DNA Recombinante/isolamento & purificação , Escherichia coli/genética , Saccharomyces cerevisiae/genética , Especificidade da Espécie , Especificidade por Substrato , Transformação GenéticaAssuntos
Mapeamento Cromossômico/métodos , Eletroforese em Gel de Campo Pulsado/métodos , Fungos/genética , Micologia/métodos , Autorradiografia/métodos , Southern Blotting/métodos , Sondas de DNA , DNA Fúngico/genética , Genes Fúngicos , Hibridização In Situ/métodos , Saccharomyces cerevisiae/genéticaRESUMO
The chromosomal locations of four glucoamylase-specifying genes in the yeast Saccharomyces cerevisiae have been determined. Chromosomes were separated by pulsed field gel electrophoresis and blots were probed with radiolabelled STA2 and marker DNA from specific yeast chromosomes. The three genes encoding extracellular glucoamylases, STA1 (DEX2), STA2 (DEX1) and STA3 (DEX3) are located on chromosomes IV, II and XIV, respectively. SGA, specifying the sporulation-specific glucoamylase, was positioned on chromosome IX.
