GeneScreen最新文献

{"title":"Mapping of genes and ESTs assigned to 17q11.2 to a YAC contig centred on the NF1 gene","authors":"Lucia Corrado,&nbsp;Paola Riva,&nbsp;Marco Venturin,&nbsp;Angela Bentivegna,&nbsp;Cristina Gervasini,&nbsp;Lidia Larizza","doi":"10.1046/j.1466-9218.2000.00002.x","DOIUrl":"10.1046/j.1466-9218.2000.00002.x","url":null,"abstract":"<p><b>Background</b> The 17q11.2 cytogenetic band is partially covered by the WC17.3 YAC contig, but the position on this contig of many D-segments, genes and ESTs assigned to the region is not unambiguous. A major reference gene of the region is NF1, involved in neurofibromatosis type 1 and deleted with flanking genes in a subset of patients with NF1 microdeletion syndrome. Several genes of medical relevance also map to the 17q11.2 band.</p><p><b>Methods</b> We assigned genes, markers and ESTs mapped to the 17q11.2 cytogenetic band to selected YACs and PACs by PCR screening and Southern hybridization of PFGE blots. YAC chimerism was detected by FISH which also allowed the refining of gene/marker order. New STSs were generated by cloning and sequencing Alu–Alu or Alu–vector fragments obtained from YACs.</p><p><b>Results</b> A &gt; 7 Mb contig centred on the <i>NF1</i> gene and consisting of 26 YACs and 8 PACs has been built up to cover most of the 17q11.2 cytogenetic band. Within the contig, we ordered 11 known and 8 novel STSs, 18 ESTs and 11 known genes, a few of which are involved in genetic diseases. Additional genes loosely assigned to 17q11.2 could be located outside the contig. The contig clones with the wide panel of anchored STSs, genes and ESTs provide a tool for the FISH characterization of gross deletions in NF1 patients with complex phenotypes and any constitutional/somatic chromosomal rearrangement affecting 17q11.2. Crosslinking of the telomeric side of our contig to the centromeric side of the nearby <i>chemokine</i> contig has been established, thus providing a long-range integrated map for the isolation of disease genes and the construction of a transcription map.</p>","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"21-27"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00002.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74492161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The histamine 1 and histamine 2 receptor genes—candidates for schizophrenia and clozapine drug response","authors":"D. Mancama,&nbsp;M. J. Arranz,&nbsp;J. Munro,&nbsp;A. Makoff,&nbsp;R. Kerwin","doi":"10.1046/j.1466-9218.2000.00005.x","DOIUrl":"10.1046/j.1466-9218.2000.00005.x","url":null,"abstract":"<p><b>Introduction</b> There is growing evidence to suggest the involvement of histaminergic pathways in the pathophysiology of schizophrenia. Overactive histamine activity is thought to contribute significantly to deficit symptoms such as apathy and social withdrawal associated with the disorder, while the efficacy of certain atypical antipsychotics may include their action at histamine receptors. By selecting the histamine 1 (<i>H1</i>) and histamine 2 (<i>H2</i>) receptor genes as candidates, the aim of this study was to investigate the possible involvement of these receptors both in schizophrenia and in the clinical response of patients undergoing clozapine treatment.</p><p><b>Method</b> Using single strand conformation polymorphism (SSCP) analysis we screened the complete coding region of each receptor gene for mutations in 50 schizophrenics and 50 unaffected individuals. Automated sequencing was used to confirm the presence and nature of each detected polymorphism.</p><p><b>Results</b> We report here the identification of five previously undescribed <i>H1</i> receptor polymorphisms (<i>Lys19Asn</i>, <i>Asp349Glu</i>, <i>1068-A/G</i>, <i>Phe358</i>Δ and <i>Leu449Ser</i>) and a single novel <i>H2</i> receptor polymorphism (<i>543-G/A</i>). Initial analysis of these polymorphisms in case vs. control association studies revealed a significant increase in distribution of one, the <i>H1</i><i>Ser449</i> allele, in our control sample (13/97) compared with the group of schizophrenics (0/90), prompting further analysis of this polymorphism in an extended patient sample population. Overall we observed a trend towards increased frequency of this allele amongst our controls compared with the corresponding group of schizophrenics, though the significance was estimated to be marginal (χ² = 3.94, <i>P</i> = 0.047). Similarly, no conclusive evidence could be found to suggest the involvement of any other <i>H1</i> and <i>H2</i> receptor variants in schizophrenia or clozapine response. Further investigation of the five polymorphic <i>H1</i> loci by haplotype analysis indicated a lack of association between these loci and both schizophrenia and clozapine response.</p><p><b>Conclusions</b> These results suggest that histamine <i>H1</i> and <i>H2</i> receptor variants do not bear significant influence on the susceptibility of individuals to schizophrenia, nor do they appear to influence clinical response to clozapine treatment.</p>","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00005.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78691153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syntenic mapping of human disease genes using animal models of autoimmunity","authors":"Anne Barton,&nbsp;Jane Worthington,&nbsp;W. E. R. Ollier","doi":"10.1046/j.1466-9218.2000.00008.x","DOIUrl":"10.1046/j.1466-9218.2000.00008.x","url":null,"abstract":"","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"3-7"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00008.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78495115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a new connexin gene GJA11 (Cx59) using degenerate PCR primers","authors":"Paul J. Coucke,&nbsp;Lut Van Laer,&nbsp;Johan Meyers,&nbsp;Peter Van Hauwe,&nbsp;Natacha Ottschytsch,&nbsp;Jan G. Wauters,&nbsp;Philip Kelley,&nbsp;Patrick J. Willems,&nbsp;Guy Van Camp","doi":"10.1046/j.1466-9218.2000.00006.x","DOIUrl":"10.1046/j.1466-9218.2000.00006.x","url":null,"abstract":"<p><b>Introduction</b> Connexins (Cx) comprise a family of homologous proteins that are involved in the intercellular exchange of ions and small metabolites between adjacent cells. So far, mutations in seven different connexins have been found in humans, each resulting in a genetic disease.</p><p><b>Methods</b> Based on the sequence alignment of known human Cx genes, we developed degenerate PCR primers that we anticipated would amplify members of the Cx gene family, in order to identify novel Cx genes.</p><p><b>Results</b> By subcloning and sequencing the PCR products, we identified a previously unidentified connexin gene that we named <i>Cx59</i> (<i>GJA11</i>). Using FISH we localized the <i>GJA11</i> gene to chromosome 1p34, and by the analysis of a YAC contig of this region, we mapped this gene within the linkage interval of an Indonesian family with autosomal dominant nonsyndromic hearing loss (ADNSHL). Because mutations in other connexins, namely <i>GJB3</i> (<i>Cx31</i>) and <i>GJB6</i> (<i>Cx30</i>), lead to similar forms of ADNSHL, <i>GJA11</i> (<i>Cx59</i>) was a very strong candidate gene. Therefore, we performed mutation analysis of the coding region of <i>GJA11</i> in patients of this Indonesian family, but no disease-causing mutation was found.</p>","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"35-40"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00006.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82647276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A candidate gene study of F cell levels in sibling pairs using a joint linkage and association analysis","authors":"Chad Garner,&nbsp;Thanusak Tatu,&nbsp;Laurence Game,&nbsp;Lon R. Cardon,&nbsp;Tim D. Spector,&nbsp;Martin Farrall,&nbsp;Swee Lay Thein","doi":"10.1046/j.1466-9218.2000.00001.x","DOIUrl":"10.1046/j.1466-9218.2000.00001.x","url":null,"abstract":"<p><b>Introduction</b> Fetal haemoglobin (Hb F) and fetal cell (FC) levels in adults show considerable variation and the heritability of FC levels has been estimated to be 89% in the healthy European population; measured genotype analyses have shown the trait to be influenced by several genetic factors. In addition to the β-globin gene complex on chromosome 11p, linkage analyses have reported loci affecting FC levels on chromosomes Xp22.2–p22.3 and 6q23.</p><p><b>Methods</b> We have genotyped a sample of approximately 300 unselected, same sex, dizygotic twin pairs from the St. Thomas’ UK Adult Twin Register for markers in these three regions and carried out a linkage analysis of FC levels. We also used a new method to simultaneously test for linkage and allelic association, and association caused by population stratification or admixture.</p><p><b>Results</b> There was no evidence for linkage of FC levels to chromosomes Xp22.2–p22.3 and 6q23. However, the β-globin cluster was shown to be significantly linked and to be responsible for approximately one-third of the additive genetic variance in FC levels in the sample.</p><p><b>Conclusions</b> The report represents the first application of this method to a sample of nonsimulated data and demonstrates the effectiveness of the approach. Combined linkage and association analysis of the β-globin complex showed a strong association between the <i>Xmn</i>I-^Gγ site and FC levels and that the observed association is not an artifact of recent population admixture or stratification.</p>","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"9-14"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00001.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57739823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic structure of the mouse trefoil factor (Tff) gene cluster in 17q","authors":"Tuncay Kayademir,&nbsp;Ian Rosewell,&nbsp;Nikolaus Blin,&nbsp;Peter Gött","doi":"10.1046/j.1466-9218.2000.00004.x","DOIUrl":"10.1046/j.1466-9218.2000.00004.x","url":null,"abstract":"<p><b>Introduction</b> In vertebrates, trefoil factor (TFF) domain peptides constitute a class of peptides secreted by the mucous epithelia of the gastrointestinal tract. These peptides promote healing and protection in the gastrointestinal tract. Since the three known human genes are clustered in 21q22.3, a similar arrangement in a paralogous region was possible in mice. The murine intestinal trefoil factor is encoded by the gene <i>Tff3</i> and was mapped to murine chromosome 17.</p><p><b>Materials and methods</b> Three bacterial and one yeast artificial chromosome recombinants (BAC and YAC) were identified and used for characterisation by PCR, restriction mapping, hybridisation, and fluorescence <i>in situ</i> hybridisation (FISH).</p><p><b>Results and discussion</b> Here we have characterised the genomic structure of all three mouse <i>Tff</i> genes starting with a contig formed by one YAC and three BACs. In a similar fashion to the <i>TFF</i> gene cluster in humans, the <i>Tff</i> genes cover a region of approx. 40 kb in the transcriptional order <i>Tff1–Tff2–Tff3</i> and localised on mouse chromosome 17. Based on this conserved genomic structure, we propose a model of how mammalian TFF genes may have evolved by exon duplication and unequal crossing over.</p>","PeriodicalId":100575,"journal":{"name":"GeneScreen","volume":"1 1","pages":"15-19"},"PeriodicalIF":0.0,"publicationDate":"2001-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1466-9218.2000.00004.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73461227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}