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At least 613 records · Page 34Linked to original sources
PubMed2001

A genome screen for multiple sclerosis in Sardinian multiplex families.

The prevalence of multiple sclerosis in Sardinia is significantly higher than in neighbouring Mediterranean countries, suggesting that the isolated growth of the population has concentrated genetic factors which increase susceptibility to the disease. The distinct HLA association of multiple sclerosis in Sardinia supports this interpretation. We have performed a whole genome screen for linkage in 49 Sardinian multiplex families using 327 markers. Non parametric linkage analysis of these data reveal suggestive linkage in the region of Chr 1q31, Chr 10q23 and Chr 11p15.

Genetic Linkage↗
PubMed2000

Identification of high affinity Tbf1p-binding sites within the budding yeast genome.

The yeast TBF1 gene is essential for mitotic growth and encodes a protein that binds the human telomere repeats in vitro, although its cellular function is unknown. The sequence of the DNA-binding domain of Tbf1p is more closely related to that of the human telomeric proteins TRF1 and TRF2 than to any yeast protein sequence, yet the functional homologue of TRF1 and TRF2 is thought to be Rap1p. In this study we show that the Tbf1p DNA-binding domain can target the Gal4 transactivation domain to a (TTAGGG)(n) sequence inserted in the yeast genome, supporting the model that Tbf1p binds this sub-telomeric repeat motif in vivo. Immunofluorescence of Tbf1p shows a spotty pattern throughout the interphase nucleus and along synapsed chromosomes in meiosis, suggesting that Tbf1p binds internal chromosomal sites in addition to sub-telomeric regions. PCR-assisted binding site selection was used to define a consensus for high affinity Tbf1p-binding sites. Compilation of 50 selected oligonucleotides identified the consensus TAGGGTTGG. Five potential Tbf1p-binding sites resulting from a search of the total yeast genome were tested directly in gel shift assays and shown to bind Tbf1p efficiently in vitro, thus confirming this as a valid consensus for Tbf1p recognition.

Base Sequence↗
PubMed2003

Presence of active aliphatic amidases in Helicobacter species able to colonize the stomach.

Ammonia production is of great importance for the gastric pathogen Helicobacter pylori as a nitrogen source, as a compound protecting against gastric acidity, and as a cytotoxic molecule. In addition to urease, H. pylori possesses two aliphatic amidases responsible for ammonia production: AmiE, a classical amidase, and AmiF, a new type of formamidase. Both enzymes are part of a regulatory network consisting of nitrogen metabolism enzymes, including urease and arginase. We examined the role of the H. pylori amidases in vivo by testing the gastric colonization of mice with H. pylori SS1 strains carrying mutations in amiE and/or amiF and in coinfection experiments with wild-type and double mutant strains. A new cassette conferring resistance to gentamicin was used in addition to the kanamycin cassette to construct the double mutation in strain SS1. Our data indicate that the amidases are not essential for colonization of mice. The search for amiE and amiF genes in 53 H. pylori strains from different geographic origins indicated the presence of both genes in all these genomes. We tested for the presence of the amiE and amiF genes and for amidase and formamidase activities in eleven Helicobacter species. Among the gastric species, H. acinonychis possessed both amiE and amiF, H. felis carried only amiF, and H. mustelae was devoid of amidases. H. muridarum, which can colonize both mouse intestine and stomach, was the only enterohepatic species to contain amiE. Phylogenetic trees based upon the sequences of H. pylori amiE and amiF genes and their respective homologs from other organisms as well as the amidase gene distribution among Helicobacter species are strongly suggestive of amidase acquisition by horizontal gene transfer. Since amidases are found only in Helicobacter species able to colonize the stomach, their acquisition might be related to selective pressure in this particular gastric environment.

Amidohydrolases↗
PubMed1995

Molecular cloning of mei-41, a gene that influences both somatic and germline chromosome metabolism of Drosophila melanogaster.

The mei-41 gene of Drosophila melanogaster plays an essential role in meiosis, in the maintenance of somatic chromosome stability, in postreplication repair and in DNA double-strand break repair. This gene has been cytogenetically localized to polytene chromosome bands 14C4-6 using available chromosomal aberrations. About 60 kb of DNA sequence has been isolated following a bidirectional chromosomal walk that extends over the cytogenetic interval 14C1-6. The breakpoints of chromosomal aberrations identified within that walk establish that the entire mei-41 gene has been cloned. Two independently derived mei-41 mutants have been shown to carry P insertions within a single 2.2 kb fragment of the walk. Since revertants of those mutants have lost the P element sequences, an essential region of the mei-41 gene is present in that fragment. A 10.5 kb genomic fragment that spans the P insertion sites has been found to restore methyl methanesulfonate resistance and female fertility of the mei-41D3 mutants. The results demonstrate that all the sequences required for the proper expression of the mei-41 gene are present on this genomic fragment. This study provides the foundation for molecular analysis of a function that is essential for chromosome stability in both the germline and somatic cells.

Animals↗
PubMed1998

AtGDI2, a novel Arabidopsis gene encoding a Rab GDP dissociation inhibitor.

The GTPase cycle of Rab/Ypt proteins is strictly controlled by several classes of regulators to ensure their proper roles in membrane traffic. GDP dissociation inhibitor (GDI) is known to play essential roles in regulating nucleotide states and subcellular localizations of Rab/Ypt proteins. To obtain further knowledge on this regulator molecule in plants, we isolated and characterized two genes of Arabidopsis thaliana that encode different GDIs. AtGDI1 has been identified by a novel functional cloning in yeast [Ueda et al. (1996) Plant Cell, 8, 2079-2091] and AtGDI2 was isolated by cross-hybridization in this study. AtGDI2, as well as AtGDI1, complements the yeast sec19/gdi1 mutant, indicating that they can replace the function of yeast GDI. Evidence is shown that both AtGDI1 and AtGDI2 can interact with Ara4, an Arabidopsis Rab protein, in the yeast ypt1 mutant cells. AtGDI2 is ubiquitously expressed in Arabidopsis tissues with some difference from AtGDI1 in expression level. Genomic DNA hybridization using specific probes reveals the presence of one more GDI gene in Arabidopsis. This may imply differentiated roles of GDI in higher plants.

Amino Acid Sequence↗
PubMed2005

Does resistance to pyrazinamide accurately indicate the presence of Mycobacterium bovis?

Mycobacterium bovis is best identified by screening those isolates of the Mycobacterium tuberculosis complex that have any pyrazinamide (PZA) resistance, using a confirmatory test such as spoligotyping, biochemical testing, or genomic deletion analysis. The sensitivity for detection of M. bovis is lowered to 82% when only PZA-monoresistant isolates are screened.

Adult↗
PubMed2001

The essential HupB and HupN proteins of Pseudomonas putida provide redundant and nonspecific DNA-bending functions.

A protein mixture containing two major components able to catalyze a beta-recombination reaction requiring nonspecific DNA bending was obtained by fractionation of a Pseudomonas putida extract. N-terminal sequence analysis and genomic data base searches identified the major component as an analogue of HupB of Pseudomonas aeruginosa and Escherichia coli, encoding one HU protein variant. The minor component of the fraction, termed HupN, was divergent enough from HupB to predict a separate DNA-bending competence. The determinants of the two proteins were cloned and hyperexpressed, and the gene products were purified. Their activities were examined in vitro in beta-recombination assays and in vivo by complementation of the Hbsu function of Bacillus subtilis. HupB and HupN were equally efficient in all tests, suggesting that they are independent and functionally redundant DNA bending proteins. This was reflected in the maintenance of in vivo activity of the final sigma54 Ps promoter of the toluene degradation plasmid, TOL, which requires facilitated DNA bending, in DeltahupB or DeltahupN strains. However, hupB/hupN double mutants were not viable. It is suggested that the requirement for protein-facilitated DNA bending is met in P. putida by two independent proteins that ensure an adequate supply of an essential cellular activity.

Amino Acid Sequence↗
PubMed1995

Identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of Leishmania donovani mutants.

A powerful approach for identifying the genes involved in the infectious cycle of pathogens is functional genetic complementation. Here, the current status of this technology in Leishmania is reviewed, focusing on the genes involved in the biosynthesis of the unique parasite surface glycolipid, lipophosphoglycan (LPG). LPG plays multiple roles in the Leishmania infectious cycle, in both the sand fly vector and in establishing successful intracellular parasitism within the vertebrate macrophage. The emerging methods for generating LPG mutations and for recovering the affected gene(s) by complementation with an episomal genomic Leishmania DNA library are reviewed. The properties and probable roles of the first two genes identified by this methodology are discussed. These methods also show great promise in the search for genes affecting other virulence factors of Leishmania as well as in the identification of new drug-resistance loci.

Animals↗
PubMed2003

A meta-analysis of whole genome linkage screens in multiple sclerosis.

Linkage studies in complex diseases like multiple sclerosis, where the effects attributable to individual loci are modest, are critically dependent upon the number of families included. We have combined the raw genotyping data from all published genome linkage screens in multiple sclerosis and thereby performed a linkage analysis including 719 families studied with a weighted average of 359 microsatellite markers per family (range 257-453) providing an average marker separation of 10.2 cM. Linkage with genome-wide significance is confirmed in the HLA region on chromosome 6p21. In addition, two novel regions suggestive of linkage are seen (17q21 and 22q13). Our simulations would imply that the number of peaks with NPL scores >/=2.1 exceeds the number expected by chance alone.

Alleles↗
PubMed1995

An isoleucyl-tRNA synthetase gene from Campylobacter jejuni.

A complete isoleucyl-tRNA synthetase gene (ileS) of Campylobacter jejuni was isolated from a C. jejuni TGH9011 genomic DNA library constructed in pBluescript. The complete coding sequence, flanking regions and transcription start point were determined. The deduced isoleucyl-tRNA synthetase (IleRS) had 917 amino acids with a molecular mass of 105,399 Da, which was consistent with the observed size of 105 kDa in Escherichia coli maxicells. The ileS gene was mapped onto the physical map of the C. jejuni genome. Alignment of the C. jejuni IleRS sequence with six other bacterial IleRS sequences and two lower eukaryotic IleRS sequences identified seven conserved motifs, including the two signature sequences, HIGH and KMSKS, of class I aminoacyl-tRNA synthetases.

Amino Acid Sequence↗
PubMed2003

Policy before practice: genetic discrimination reviewed.

The value of genetics in medicine has been steadily developing with our increasing knowledge of the human genome. Genetic testing to determine disease risk or potential drug effects is set to become more commonplace. With this comes increasing concern about access to genetic information, and the potential for discriminatory usage of such information. At present, the scope and predictability of genetic testing and the conclusions that may be drawn fairly from genetic information are limited. Nonetheless, public concerns about discrimination based on the possession of a genetic trait or condition are well documented. The prospect that such information might be used in decisions regarding employment or insurability has caused anxiety and prompted legislation largely dedicated to the use of information about one's genotype rather than medical information in general. These laws emphasize genetic information as distinct from other medical information and attempt to prioritize interests in genetic information. As the distinction between genetic and medical information becomes untenable, those who would regulate the use of genotypic information will find this approach to policy problematic.In considering the limits of legislation as an effective tool of regulating genetic discrimination, several conclusions can be drawn: firstly, despite the promise of genomic medicine, current knowledge is insufficient to justify the use or application of certain genetic information in nonmedical contexts; secondly, public resistance to genomic medicine that is based on fear of genetic discrimination poses a danger that justifies a policy response; and thirdly, such a response may be purely symbolic and not entirely effective, provided that the policy establishes a consensus regarding the applicability of genetic information in nonmedical contexts.

Genetic Testing↗
PubMed2001

Novel genomic locus with atypical G+C content that is required for extracellular polysaccharide production and virulence in Xanthomonas oryzae pv. oryzae.

Three exopolysaccharide (EPS)- and virulence-deficient mutants of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight of rice, were isolated by Tn5 mutagenesis. These insertions are not located within the gum gene cluster. A 40-kb cosmid clone that restored EPS production and virulence to all three mutants was isolated, and the three transposon insertions were localized to contiguous 4.3- and 3.5-kb EcoRI fragments that are included in this clone. Sequence data indicate that two of the transposon insertions are in genes that encode a putative sugar nucleotide epimerase and a putative glycosyl transferase, respectively; the third insertion is located between the glycosyl transferase gene and a novel open reading frame (ORF). A 5.5-kb genomic region in which these three ORFs are located has a G+C content of 5-1.7%, quite different from the G+C content of approximately 65.0% that is typical of X. oryzae pv. oryzae. Homologues of this locus have not yet been reported in any other xanthomonad.

Base Composition↗
PubMed1990

A combined physical and genetic map of Pseudomonas aeruginosa PAO.

A combined physical and genetic map of Pseudomonas aeruginosa PAO was constructed by pulsed-field gel electrophoresis and Southern hybridization using cosmid clones from a genomic library carrying known genes. A total of 37 SpeI restriction fragments have been mapped on the 5862 kb genome, and fragment contiguity demonstrated by hybridization with clones from a SpeI junction fragment library and fragments obtained by partial SpeI digestion, both derived from the P. aeruginosa PAO chromosome.

Blotting, Southern↗
PubMed2003

Age-stratified QTL genome scan analyses for anthropometric measures.

With the availability of longitudinal data, age-specific (stratified) or age-adjusted genetic analyses have the potential to localize different putative trait influencing loci. If age does not influence the locus-specific penetrance function within the range examined, age-stratified analyses will tend to yield comparable results for an individual trait. However, age-stratified results should vary across age strata when the locus-specific penetrance function is age dependent. In this paper, age-stratified and age-adjusted quantitative trait loci (QTL) linkage analyses were contrasted for height, weight, body mass index (BMI), and systolic blood pressure on a subset of the Framingham Heart Study. The strata comprised individuals with data present in each of three age groups: 31-49, 50-60, 61-79. Genome-wide QTL analyses were performed using SOLAR. Over all ages, a linkage signal for height was detected on chromosome 14q11.2 near marker GATA74E02A (LOD for ages 31-49 = 2.38, LOD for ages 50-60 = 1.84, LOD for ages 61-79 = 2.45). Evidence of linkage to BMI in the 31-49 age group was found on chromosome 3q22 (GATA3C02, LOD = 2.89, p = 0.0003) at the same location as the signal for weight (LOD = 3.10, p = 0.0002). Linkage was also supported on chromosome 1p22.1 for BMI (LOD = 2.21, p = 0.0014) and weight (LOD = 2.47, p = 0.0007) in the 31-49 age group. Our age-stratified results suggest that QTL that are expressed over long periods of time and affecting multiple, correlated traits may be identified using genome scan and variance-component methodology to help detect early and/or late gene expression.

Adult↗
PubMed2006

Results of a SNP genome screen in a large Costa Rican pedigree segregating for severe bipolar disorder.

We have ascertained in the Central Valley of Costa Rica a new kindred (CR201) segregating for severe bipolar disorder (BP-I). The family was identified by tracing genealogical connections among eight persons initially independently ascertained for a genome wide association study of BP-I. For the genome screen in CR201, we trimmed the family down to 168 persons (82 of whom are genotyped), containing 25 individuals with a best-estimate diagnosis of BP-I. A total of 4,690 SNP markers were genotyped. Analysis of the data was hampered by the size and complexity of the pedigree, which prohibited using exact multipoint methods on the entire kindred. Two-point parametric linkage analysis, using a conservative model of transmission, produced a maximum LOD score of 2.78 on chromosome 6, and a total of 39 loci with LOD scores >1.0. Multipoint parametric and non-parametric linkage analysis was performed separately on four sections of CR201, and interesting (nominal P-value from either analysis <0.01), although not statistically significant, regions were highlighted on chromosomes 1, 2, 3, 12, 16, 19, and 22, in at least one section of the pedigree, or when considering all sections together. The difficulties of analyzing genome wide SNP data for complex disorders in large, potentially informative, kindreds are discussed.

Bipolar Disorder↗
PubMed2005

Whole-genome screening for susceptibility genes in multicase families with Behçet's disease.

OBJECTIVE: Behçet's disease is generally considered to be a multifactorial disease with important genetic and environmental components. A strong association between an HLA class I antigen, HLA-B51, and Behçet's disease has long been known. However, analysis of multicase families has suggested a substantial contribution of non-HLA loci. The aim of this study was to perform a whole-genome linkage analysis for identification of other susceptibility loci for Behçet's disease in multicase families. METHODS: The study group comprised a total of 193 individuals (90 male, 103 female) from 28 multicase families of Turkish origin; 83 of the subjects (50 males, 33 females) fulfilled the International Study Group criteria for Behçet's disease. Three hundred ninety-five highly informative microsatellite markers spanning the genome were genotyped using fluorescent polymerase chain reaction primers and a fully automated electrophoresis platform. After the first analysis, 33 additional markers that were located close to the peak linkage areas were genotyped in all individuals. Nonparametric multipoint linkage analysis was carried out using GeneHunter version 2.1 software. RESULTS: Evidence for linkage (P < or = 0.05) was obtained in 16 chromosome regions: 1p36, 4p15, 5q12, 5q23, 6p22-24, 6q16, 6q25-26, 7p21, 10q24, 12p12-13, 12q13, 16q12, 16q21-23, 17p13, 20q12-13, and Xq26-28. After the addition of further markers, the maximum nonparametric linkage score increased from 3.5 to 3.94 at 12p12-13 (D12S77; P = 0.0002) and from 3.07 to 3.70 at 6p22-24 (D6S285; P = 0.0005). CONCLUSION: This study is the first systematic genome screen in Behçet's disease and provides evidence of linkage to several non-HLA susceptibility loci in a cohort of Turkish multicase families. This represents the first step toward the identification of novel Behçet's disease susceptibility genes.

Behcet Syndrome↗
PubMed2003

Genomic regions linked to alcohol consumption in the Framingham Heart Study.

BACKGROUND: Pedigree, demographic, square-root transformed maximum alcohol (SRMAXAPD) and maximum cigarette (MAXCPD) consumption, and genome-wide scan data from the Framingham Heart Study (FHS) were used to investigate genetic factors that may affect alcohol and cigarette consumption in this population-based sample. RESULTS: A significant sister:sister correlation greater than spouse correlation was observed for MAXCPD only. Single-point sib-pair regression analysis provided nominal evidence for linkage of loci to both SRMAXAPD and MAXCPD consumption traits, with more significant evidence of linkage to SRMAXAPD than to MAXCPD. One genomic region, chr9q21.11, exhibits significant multi-point sib-pair regression to SRMAXAPD. CONCLUSION: SRMAXAPD exhibits greater evidence for genetic linkage than does MAXCPD in the FHS sample. Four regions of the genome exhibiting nominal evidence for linkage to SRMAXAPD in the FHS sample correspond to regions of the genome previously identified as linked to alcoholism or related traits in the family data set ascertained on individuals affected with alcohol dependence known as COGA.

Alcohol Drinking↗
PubMed2000

[Progress in pediatric neurology].

A central part of Pediatric Neurology is currently dominated by the search for genetic factors involved in developmental disorders of the nervous system, including cases where the cytogenetic examination remains uncontributive. The prerequisite for a good definition of the malformative phenotypes leads to distinguish: 1 cerebral malformations that can be identified at the macroscopic scale, by imaging. 2 polymalformative syndromes including mental retardation where cerebral imaging is not contributive, thus the syndromatic definition is based on associated somatic anomalies. 3 Non-syndromatic mental retardation, where a genetic origin is clear only in the familial forms. Various methodological approaches have included genetic linkage studies, search for inframicroscopic chromosomal rearrangements in the critical region and investigation of candidate genes. A great number of syndromes have been connected with a great diversity of genetic mechanisms, whose many examples are presented: genopathies with regular or variable expression, unstable mutations, contiguous gene syndromes or other complex infracytogenetic rearrangements, chromosomal or genic mosaicisms, mutations submitted to parental imprinting. New methods of genomic screening will be necessary to progress in this field, given the great number of genes involved in cerebral development. As for the early developmental disorders of the PNS and muscle, their diagnosis becomes frequent during the intrauterine life, raising the problem of a better definition of the fetopathological phenotypes.

Abnormalities, Multiple↗