RESUMO
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
Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered. It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped. However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II. The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.
Assuntos
Cromossomos Fúngicos , Saccharomyces cerevisiae/genética , Sequência de Bases , DNA Fúngico , Fases de Leitura AbertaRESUMO
A new member of the 2-micron family of plasmids, named pTD1, was found in the yeast Torulaspora delbrueckii, a widespread yeast associated with food. Nucleotide sequences revealed the presence of a pair of inverted repeats and three open reading frames, one of which is a homologue of the FLP recombinase gene of 2-micron plasmid. An ARS region was identified, by replication in Saccharomyces cerevisiae and T. delbrueckii, near one of the inverted repeats. By the use of pTD1 derivatives and auxotrophic mutant hosts an efficient host-vector system was established for T. delbrueckii. So far, the 2-micron family of plasmids is restricted to four closely related genera (Q6 group): Saccharomyces, Zygosaccharomyces, Kluyveromyces, and Torulaspora. After a survey of 2500 strains belonging to about 500 species (80 genera) of yeast, no circular plasmids were found in other genera.
Assuntos
Ascomicetos/genética , DNA Fúngico , Plasmídeos , Sequência de Bases , Clonagem Molecular , Replicação do DNA , Frequência do Gene , Vetores Genéticos , Dados de Sequência MolecularRESUMO
The nucleotide sequence of a 37 000 base pair region from the left arm of chromosome XV of Saccharomyces cerevisiae has been determined and analysed. This region contains 21 open reading frames (ORFs) coding for proteins of more than 100 amino acids. Six ORFs correspond to the genes PAC1, VPH1, MOD5, CAP20, ORF1 and SNF2 already described. Eight ORFs show some similarities to known genes from yeast and other organisms. They include genes coding for serine/threonine protein kinases, a multidrug resistance family homologue, a protein related to dihydrofolate reductase, a cluster of heat shock-like proteins and a gene coding for an enzyme related to protein disulfide isomerase. Finally seven ORFs do not show any similarities with a known gene. In addition we found a new ala-tRNA (UGC) gene located next to a sigma sequence.
Assuntos
Cromossomos Fúngicos/genética , DNA Fúngico/genética , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Animais , Mapeamento Cromossômico , Proteínas Fúngicas/genética , Genes Fúngicos , Genes MDR , Proteínas de Choque Térmico/genética , Isomerases/genética , Dados de Sequência Molecular , Família Multigênica , Fases de Leitura Aberta , Isomerases de Dissulfetos de Proteínas , Proteínas Serina-Treonina Quinases/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Tetra-Hidrofolato Desidrogenase/genéticaRESUMO
The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.
Assuntos
Cromossomos Fúngicos , DNA Fúngico , Saccharomyces cerevisiae/genética , Sequência de Bases , Mapeamento Cromossômico , Proteínas Fúngicas/genética , Fases de Leitura AbertaRESUMO
The nucleotide sequence of a 19,000 base pair region from the left arm of chromosome XI of Saccharomyces cerevisiae has been determined and analysed. It covers the HAP4-GFA1-LAP4 loci already described. As expected HAP4, GFA1 and LAP4 genes have been found and six new open reading frames (ORFs) with a coding capacity of more than 100 amino acid residues have been identified. One of them (YKL461) shows a high degree of identity with an aspartate aminotransferase gene. This raises the question of a second aspartate aminotransferase gene in yeast. A second ORF (YKL462) shows features compatible with a membranous localization. The other ORFs do not show a similarity with any known gene. A member of the highly repetitive 'CAT' DNA sequence is present.
Assuntos
Aspartato Aminotransferases/genética , DNA Fúngico/genética , Genes Fúngicos , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Sequência de Bases , Dados de Sequência Molecular , Família Multigênica , Fases de Leitura Aberta , Sequências Repetitivas de Ácido Nucleico , Mapeamento por RestriçãoRESUMO
We report in this paper the sequence of a part of chromosome XI of Saccharomyces cerevisiae. This 17 kbp nucleotide sequence represents the right half of cosmid pUKG151 and contains nine open reading frames, YKL453, 450, 449, 448, 445, 443, 442, 441 and the 5' part of YKL440. YKL440 was previously identified as the MBR1 gene and plays a role in mitochondrial biogenesis. YKL443 is a homologue of the yeast serine-rich protein (SRP1), while YKL453 presents strong homologies with the KIN1/KIN2/SNF1 kinase family. It must be pointed out that the size of this gene is well above average for yeast.
Assuntos
Mapeamento Cromossômico , Genes Fúngicos , Saccharomyces cerevisiae/genética , Análise de Sequência de DNA , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Fúngicos , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Dados de Sequência Molecular , Fases de Leitura Aberta , Proteínas Quinases/química , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Homologia de Sequência do Ácido NucleicoRESUMO
A 6.8 kbp DNA fragment localized to the left arm of chromosome XI from Saccharomyces cerevisiae was sequenced and analysed (EMBL accession no. X69765). Two genes involved in protein phosphatase activity were identified: YCN2 and an open reading frame encoding a protein that shares 46% amino acid identity with the sds22+ protein from Schizosaccharomyces pombe. A comparison of the genomic YCN2 sequence with the published cDNA sequence suggests the presence of an intron near the 5' end of the gene. Further sequence analysis suggests the presence of three additional genes near YCN2: a mitochondrial acyl-carrier protein, a gene encoding a putative hydrophobic protein, and a new gene coding for a tRNA(Leu) (UAA) isoacceptor located near a delta sequence.
Assuntos
Cromossomos Fúngicos , DNA Fúngico/genética , Genes Fúngicos/genética , Saccharomyces cerevisiae/genética , Proteína de Transporte de Acila/genética , Sequência de Aminoácidos , Sequência de Bases , Calcineurina , Proteínas de Ligação a Calmodulina/genética , Clonagem Molecular , Proteínas Fúngicas/genética , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Fosfoproteínas Fosfatases/genética , RNA de Transferência de Leucina/genéticaRESUMO
A 10,095 base pair DNA fragment from the right arm of chromosome III of Saccharomyces cerevisiae has been sequenced and analysed. It encompasses the silent mating-type locus HMR. Both HMRa1 and HMRa2 genes, as well as their flanking regulatory regions, have been identified. Three new open reading frames longer than 80 amino acid residues were found in this fragment. One of them (YCR137) shows features compatible with a membranous localization and a transporter function. The other two do not show a similarity with any known gene. A new gene coding for tRNA(thr)al (ACU) has been identified. It is located in a region coding for several delta sequences.