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At least 739 records · Page 41Linked to original sources
PubMed2000

Sugar uptake and utilisation in Streptomyces coelicolor: a PTS view to the genome.

Our research group is studying the phosphotransferase system (PTS) of Streptomyces coelicolor, which, in other bacteria, is centrally involved in carbon source uptake and regulation. We have surveyed the public available S. coelicolor genome sequence produced by the ongoing genome sequencing project for pts gene homologues (http://www.sanger.ac.uk/Projects/S_coelicolor/). Three genes encoding homologues of the general PTS components enzyme I (ptsI), HPr (ptsH), and enzyme IIA(Crr) (crr; IIA(Glc)-homologue) and six genes encoding homologues of sugar-specific PTS components were identified. The deduced primary sequences of the sugar-specific components shared significant similarities to PTS permeases of the mannitol/fructose family and of the glucose/sucrose family. A model is presented, in which possible functions of the novel described PTS homologues are discussed.

Amino Acid Sequence↗
PubMed2005

Genome-wide screening for genetic changes in a matched pair of benign and prostate cancer cell lines using array CGH.

Copy number alterations in a matched pair of benign epithelial and prostate cancer cell lines derived from the same patient were assessed using array-based comparative genomic hybridisation (aCGH). The cancer cell line showed a gain of chromosome 7, deletion of chromosome 8, gains (including high level) and losses on chromosome 11, loss of 18p and gain of 20q. Deletions on chromosome 8 were confirmed with microsatellite markers. The aCGH results were compared to gene expression data obtained using DNA microarrays and suggested the involvement of caspases and ICEBERG on 11q and E2F1 on chromosome 20q.

Cell Line, Tumor↗
PubMed2004

A second-generation genome screen for linkage to type 1 diabetes in a Bedouin Arab family.

IDDM17 on chromosome 10 was identified in an initial genome screen of 13 members (10 affected) of a large Bedouin Arab family that had 19 relatives affected with type 1 diabetes. Two more children have now been diagnosed with the disease. A second genome screen with 45 members (17 affected members, spouses, and offspring; 382 markers) was performed. A parallel version of Genehunter was used for parametric and nonparametric linkage analyses. The nonparametric linkage analysis (NPL) confirmed the IDDM17 locus (NPL = 3.79; P = 0.001) with a prominent LOD (logarithm of the odds = 2.38) peak. These results demonstrate the strong potential of genetically homogenous, extended families for mapping genes that contribute to a complex disease.

Arabs↗
PubMed1999

Analysis of principal component based quantitative phenotypes for alcoholism.

Principal component analysis was used to construct quantitative phenotypes for alcoholism. These were analyzed for linkage to genomic regions with a variance components approach. The four phenotypes considered were a factor describing medical symptoms of alcohol dependency, a factor describing a psychological profile correlated with susceptibility to alcoholism, monoamine oxidase B (MAOB) activity and an average measurement of the P3 component of event-related potentials (ERP) at the Fp electrode placements. One region (around marker GATA123C09 on chromosome 3) with suggestive evidence for linkage was detected for the P3 (Fp) measurement. For three of the four distinct phenotypes, modest evidence for linkage to a similar region (around marker ADH3 on chromosome 4) was found.

Alcoholism↗
PubMed2004

Characterization and genetic manipulation of peptide synthetases in Pseudomonas aeruginosa PAO1 in order to generate novel pyoverdines.

PvdD, a nonribosomal peptide synthetase (NRPS) of Pseudomonas aeruginosa PAO1, incorporates two L-threonines into the siderophore pyoverdine. A pvdD mutant did not synthesize pyoverdine and lacked a high Mr iron-regulated cytoplasmic protein (IRCP). Analysis of other IRCPs and the P. aeruginosa genome enabled the remaining pyoverdine NRPSs to be identified. The pvdD mutation could be complemented in trans, enabling design of plasmid-based systems for the generation of novel pyoverdines. Introduction of a truncated pvdD gene resulted in attenuated forms of pyoverdine, and introduction of L-threonine-incorporating NRPSs from other organisms restored pyoverdine production to mutant cells. This is the first successful rational in vivo modification of NRPS modules outside of Bacillus subtilis. The systems employed did not allow incorporation of other residues into pyoverdine, indicating that there are multiple elements contributing toward substrate specificity in NRPSs.

Amino Acid Sequence↗
PubMed2003

A genome screen for linkage disequilibrium in Turkish multiple sclerosis.

In order to screen the Turkish population for evidence of association with multiple sclerosis, we typed 6000 microsatellite markers in separately pooled DNA samples from 197 cases and 199 controls following the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) protocol. Twelve markers showing evidence for association were identified. One of these markers lying directly in a region which is also implicated in the Turkish linkage screen (chromosome 5p15) and thus shows evidence for both linkage and association in independent data sets.

Adult↗
PubMed2005

Genomic microarray analysis identifies candidate loci in patients with corpus callosum anomalies.

Absence of the corpus callosum is often associated with cognitive deficits, autism, and epilepsy. Using a genomic microarray, the authors analyzed DNA from 25 patients with radiographically confirmed callosal anomalies and identified three patients with de novo copy number changes in chromosome regions 2q37, 6qter, and 8p. Chromosomal deletions and duplications may be a relatively common cause of cerebral malformations.

Agenesis of Corpus Callosum↗
PubMed2006

Technical validation of a TM Biosciences Luminex-based multiplex assay for detecting the American College of Medical Genetics recommended cystic fibrosis mutation panel.

The American College of Medical Genetics (ACMG) and the American College of Obstetrics and Gynecology have recommended population-based carrier screening for cystic fibrosis to include 23 mutations and 5 polymorphisms in the cystic fibrosis transmembrane regulator gene(CFTR). We estimate 20% of all pregnant women are being tested for their CF carrier status. We assessed two commercially available analyte-specific reagents (ASRs) capable of testing all 25 mutations of the original ACMG-recommended panel, Tag-It CFTR40 + 4 Luminex-based reagent from Tm Biosciences, and our current assay platform, CF Genotyper V. 3.0 from Abbott/Celera. Blinded testing using genomic controls containing known CFTRmutations demonstrated that the Tag-It platform detected all mutations on the ACMG-recommended panel. We next performed a platform comparison with 1,029 consecutive patient samples. There were no discrepant results in 1,029 consecutive analyses between the two platforms, yielding an impressive figure of >25,000 individual genotypes without error for both platforms. In conclusion, both the Abbott/Celera ASR reagent and the Luminex-based Tag-It CF ASR reagent are appropriate for use in the clinical laboratory.

Alleles↗
PubMed2002

Full-speed mammalian genetics: in vivo target validation in the drug discovery process.

The completion of the Human Genome Project has signaled the beginning of the post-genome era, with a corresponding shift in focus from the sequencing and identification of genes to the exploration of gene function. A rate-limiting step in deriving value from this gene sequence information is determining the potential pharmaceutical applications of genes and their encoded proteins. This validation step is crucial for focusing efforts and resources on only the most promising targets. Strategies using reverse mouse genetics provide excellent methods for validating potential targets and therapeutic proteins in vivo in a mammalian model system.

Animals↗
PubMed2005

Association of the HLA region with multiple sclerosis as confirmed by a genome screen using >10,000 SNPs on DNA chips.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with a complex genetic background. Here, we present a genome screen for association in small scale, employing 11,555 single nucleotide polymorphisms (SNPs) on DNA chips for genotyping 100 MS patients stratified for HLA-DR2+ and 100 controls. More than 500 SNPs revealed significant differences between cases and controls before Bonferroni correction. A fraction of these SNPs was reanalysed in two additional cohorts of patients and controls, using high-throughput genotyping methods. A marker on chromosome 6p21.32 (rs2395182) yielded the highest significance level, validating the established HLA-DR association.

Genetic Linkage↗
PubMed2006

Characterization and complementation of a Fus3/Kss1 type MAPK from Tuber borchii, TBMK.

Mitogen-activated protein kinases (MAPK) are used by organisms to transduce extra cellular signals from the environment in cellular events such as proliferation and differentiation. In the present study, we have characterized the first MAPK from the ectomycorrhizal fungus Tuber borchii (TBMK) which belongs to the YERK1 (yeast extra cellular regulated kinase) subfamily. TBMK is present as a single copy in the genome and the codified protein was phosphorylated during the interaction with the host plant, Tilia americana. Complementation studies showed that TBMK restores pheromone signaling in Saccharomyces cerevisiae and partially restores invasive growth of Fusarium oxysporum that lack the fmk1 gene. This suggests a protein kinase activity and its involvement in the infection processes. Hence, TBMK could play an important role during the pre-symbiotic phase of T. borchii with its host plant in the modulation of genes necessary for the establishment of symbiosis leading to the synthesis of functional ectomycorrhizae.

Fungal Proteins↗
PubMed1993

Direct detection of novel expanded trinucleotide repeats in the human genome.

Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two-step cycling process that generates oligonucleotide multimers when expanded trinucleotide sequences are present at the level found in myotonic dystrophy and fragile-X patients. We have identified at least one new locus exhibiting trinucleotide expansion. Analysis of three families transmitting a long CTG repeat shows that the allele in these families corresponds to a locus on chromosome 18. RED constitutes a powerful tool to identify other diseases caused by this mechanism, particularly diseases associated with anticipation.

Chromosomes, Human, Pair 18↗
PubMed1993

Tobacco plants transformed with the O-acetylserine (thiol) lyase gene of wheat are resistant to toxic levels of hydrogen sulphide gas.

O-acetylserine (thiol) lyase (EC4.2.99.8) is the key enzyme in the cysteine biosynthetic pathway of plants and prokaryotes. The gene, cys1, encoding this enzyme was isolated from a wheat (Triticum aestivum L.) cDNA library, and its deduced amino acid sequence found to show 53% sequence identity with the O-acetyl-serine (thiol) lyase of Escherichia coli and Salmonella typhimurium. The deduced peptide consists of 325 amino acids (34.1 kDa), contains a conserved motif for the binding of pyridoxal phosphate, a co-factor required for enzymatic activity, and an N-terminal region of 37 amino acid residues resembling chloroplast transit peptides. The identity of cys1 was further demonstrated through complementation of an E. coli cysteine auxotroph, which lacks O-acetylserine (thiol) lyase, by expression of the wheat gene. Northern blot analysis showed that cys1 is highly expressed in green vegetative and reproductive tissues and in the roots of wheat, as well as in the leaves of several plant species. Southern blot analysis demonstrated that the gene exists as a single copy in the wheat genome. Tobacco plants transformed with cys1 in the sense orientation (sense plants) or antisense orientation (antisense plants), under the control of the CaMV 35S promoter, showed high levels of transcripts. The O-acetylserine (thiol) lyase activity in transgenic plants was determined, and found to be three- to fivefold higher in sense plants than in control plants, but unaffected in antisense transformants. Fumigation experiments with toxic levels of hydrogen sulphide (H2S) gas showed that while sense transformants were highly resistant, control and antisense plants were severely damaged by the treatment.

Amino Acid Sequence↗
PubMed1996

Natural genetic transformation in Streptococcus gordonii: comX imparts spontaneous competence on strain wicky.

Streptococcus gordonii Wicky becomes competent only after stimulation with conditioned medium from strain Challis as a source of competence factor (CF). A 3.2-kbp genomic fragment from Challis was found to impart spontaneous competence on Wicky by a complementation assay. Wicky clones containing the fragment secreted a heat-sensitive activity that induced competence in Wicky and in a comA insertion mutant of Challis. Activity was localized to a putative open reading frame, comX, with the potential to encode a 52-amino-acid peptide. comX had no similarity to known sequences, and a comX::ermAM insertion mutant of Challis transformed normally and secreted CF. These data suggest that a CF-independent pathway for competence induction exists in S. gordonii.

Amino Acid Sequence↗
PubMed2006

Development of a microsatellite marker set applicable to genome-wide screening of cynomolgus monkeys (Macaca fascicularis).

To develop a microsatellite marker set applicable to genome-wide screening of cynomolgus monkeys (Macaca fascicularis), 148 microsatellite markers were selected from the human genome database. The polymorphisms and inheritance of PCR products were determined by screening twenty unrelated monkeys and by analysis of three families, respectively. As a result, 106 primers (72%) gave PCR products of the size expected for humans and rhesus monkeys. Among these products, polymorphism and single-gene inheritance in cynomolgus monkeys was observed for 66 markers (62%). The average number of alleles at the 66 polymorphic loci was 5.86 (range 2-10), and average heterozygosity was 0.63 (range 0.10-0.88). This is the first report of microsatellite markers for cynomolgus monkeys. Chromosomal mapping of these markers is now in progress.

Animals↗
PubMed1993

Complementation of a poliovirus defective genome by a recombinant vaccinia virus which provides poliovirus P1 capsid precursor in trans.

Defective interfering (DI) RNA genomes of poliovirus which contain in-frame deletions in the P1 capsid protein-encoding region have been described. DI genomes are capable of replication and can be encapsidated by capsid proteins provided in trans from wild-type poliovirus. In this report, we demonstrate that a previously described poliovirus DI genome (K. Hagino-Yamagishi and A. Nomoto, J. Virol. 63:5386-5392, 1989) can be complemented by a recombinant vaccinia virus, VVP1 (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 65:2088-2092, 1991), which expresses the poliovirus capsid precursor polyprotein, P1. Stocks of defective polioviruses were generated by transfecting in vitro-transcribed defective genome RNA derived from plasmid pSM1(T7)1 into HeLa cells infected with VVP1 and were maintained by serial passage in the presence of VVP1. Encapsidation of the defective poliovirus genome was demonstrated by characterizing poliovirus-specific protein expression in cells infected with preparations of defective poliovirus and by Northern (RNA) blot analysis of poliovirus-specific RNA incorporated into defective poliovirus particles. Cells infected with preparations of defective poliovirus expressed poliovirus protein 3CD but did not express capsid proteins derived from a full-length P1 precursor. Poliovirus-specific RNA encapsidated in viral particles generated in cells coinfected with VVP1 and defective poliovirus migrated slightly faster on formaldehyde-agarose gels than wild-type poliovirus RNA, demonstrating maintenance of the genomic deletion. By metabolic radiolabeling with [35S]methionine-cysteine, the defective poliovirus particles were shown to contain appropriate mature-virion proteins. This is the first report of the generation of a pure population of defective polioviruses free of contaminating wild-type poliovirus. We demonstrate the use of this recombinant vaccinia virus-defective poliovirus genome complementation system for studying the effects of a defined mutation in the P1 capsid precursor on virus assembly. Following removal of residual VVP1 from defective poliovirus preparations, processing and assembly of poliovirus capsid proteins derived from a nonmyristylated P1 precursor expressed by a recombinant vaccinia virus, VVP1 myr- (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 66:4556-4563, 1992), in cells coinfected with defective poliovirus were analyzed. Capsid proteins generated from nonmyristylated P1 did not assemble detectable levels of mature virions but did assemble, at low levels, into empty capsids.(ABSTRACT TRUNCATED AT 400 WORDS)

Capsid↗
PubMed2006

Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11-q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling. METHODS AND RESULTS: 29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2-19 clones). No recurrent abnormality was identified. CONCLUSION: These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.

Adolescent↗
PubMed1994

Advances in genome research and molecular diagnostics.

A diverse scala of refined molecular techniques, developed during early positional cloning and the Human Genome project, has caused a rapid increase of our insight into the cause of genetic diseases. Nowadays, from cytogenetic rearrangements to point mutations can be readily detected by a variety of techniques. This not only has broadened our understanding, but has also enormously assisted in providing rapid and specific diagnosis, hence reducing uncertainty and improving the choices for those concerned with genetic disease in their family. While initially restricted to the DNA-level, diagnostic technology has gradually been tailored to suit the specifics of the diseases in question, incorporating RNA and protein analysis. The latest development in the analysis of genetic disease is reviewed.

Genetic Diseases, Inborn↗