Biomedical subjects

Tom I Bonner

Publications and source records attributed to Tom I Bonner.

8 recordsLinked to original sources

PubMed2005

Linkage disequilibrium analysis in the LOC93081-KDELC1-BIVM region on 13q in bipolar disorder.

Genome-wide scans in bipolar disorder and a meta analysis on published data have provided evidence for linkage to chromosome 13q, although the reported peaks from various studies have not converged in a narrow region. Recently, single nucleotide polymorphisms (SNPs) at the G72/G30 locus have been shown to be associated with bipolar disorder suggesting its potential role in increasing disease risk. The proposed linkage region on 13q extends over a wide span, and could provide a clue to the existence of other susceptibility variants. In the present study, SNPs in the LOC93081-KDELC1-BIVM, a region proximal to G72, were interrogated in two bipolar family series. KDELC1 has a predicted filamin domain and BIVM contains an immunoglobulin-like motif. The small pedigree series yielded a nominally significant global P-value due to under-transmission of a rare haplotype but this finding was not supported by results from the larger series and in the case-control study that compared 278 cases and 277 controls.

Alleles↗

PubMed2005

International Union of Pharmacology. XLVI. G protein-coupled receptor list.

NC-IUPHAR (International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification) and its subcommittees provide authoritative reports on the nomenclature and pharmacology of G protein-coupled receptors (GPCRs) that summarize their structure, pharmacology, and roles in physiology and pathology. These reports are published in Pharmacological Reviews (http://www.iuphar.org/nciuphar_arti.html) and through the International Union of Pharmacology (IUPHAR) Receptor Database web site (http://www.iuphar-db.org/iuphar-rd). The essentially complete sequencing of the human genome has allowed the cataloging of all of the human gene sequences potentially encoding GPCRs. The IUPHAR Receptor List (http://www.iuphar-db.org/iuphar-rd/list/index.htm) presents this catalog giving IUPHAR-approved nomenclature (where available), known ligands, and gene names for all of these potential receptors (excluding sensory receptors and pseudogenes) together with links to curated sequence, descriptive information, and additional links in the Entrez Gene database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene). This list is a major new initiative of NC-IUPHAR that, through continuing curation, defines the target of our ongoing receptor classification and invites further input from the scientific community.

Animals↗

PubMed2005

International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function.

Ghrelin is a 28-amino acid peptide originally isolated from rat stomach and is cleaved from a 117-amino acid precursor. The sequence of the mature peptide from rats and mice differs by two amino acids from that of human ghrelin. Alternative splicing of the ghrelin gene transcript can result in the translation of a second biologically active peptide, des-Gln14-ghrelin. Both peptides have a unique post-translational modification, octanoylation of Ser3, which is essential for the binding to receptors in hypothalamus and pituitary and stimulating the release of growth hormone from the pituitary. The growth hormone secretagogue receptor (GHS-R1a, Swiss-Prot code Q92847, LocusLink ID 2693), a rhodopsin-like seven transmembrane spanning G protein-coupled receptors belonging to Family A, was cloned in 1996 from the pituitary and hypothalamus and shown to be the target of growth hormone secretagogues (GHS), a class of synthetic peptide and nonpeptide compounds causing growth hormone release from the anterior pituitary. In 1999, ghrelin was identified as the endogenous cognate ligand for this receptor. The purpose of this review is to propose an official International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) nomenclature designating GHS-R1a as the ghrelin receptor to follow the convention of naming receptors after the endogenous agonist, abbreviated where necessary to GRLN.

Animals↗

PubMed2004

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

Animals↗

PubMed2003

DNannotator: Annotation software tool kit for regional genomic sequences.

Sequence annotation is essential for genomics-based research. Investigators of a specific genomic region who have developed abundant local discoveries such as genes and genetic markers, or have collected annotations from multiple resources, can be overwhelmed by the difficulty in creating local annotation and the complexity of integrating all the annotations. Presenting such integrated data in a form suitable for data mining and high-throughput experimental design is even more daunting. DNannotator, a web application, was designed to perform batch annotation on a sizeable genomic region. It takes annotation source data, such as SNPs, genes, primers, and so on, prepared by the end-user and/or a specified target of genomic DNA, and performs de novo annotation. DNannotator can also robustly migrate existing annotations in GenBank format from one sequence to another. Annotation results are provided in GenBank format and in tab-delimited text, which can be imported and managed in a database or spreadsheet and combined with existing annotation as desired. Graphic viewers, such as Genome Browser or Artemis, can display the annotation results. Reference data (reports on the process) facilitating the user's evaluation of annotation quality are optionally provided. DNannotator can be accessed at http://sky.bsd.uchicago.edu/DNannotator.htm.

Chromosomes, Human, Pair 13↗

PubMed2003

Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series.

Linkage evidence suggests that chromosome 13 (13q32-33) contains susceptibility genes for both bipolar disorder and schizophrenia. Recently, genes called "G72" and "G30" were identified, and polymorphisms of these overlapping genes were reported to be associated with schizophrenia. We studied two series of pedigrees with bipolar disorder: the Clinical Neurogenetics (CNG) pedigrees (in which linkage to illness had been previously reported at 13q32-33), with 83 samples from 22 multiplex families, and the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees, with 474 samples from 152 families. Sixteen single-nucleotide polymorphisms (SNPs) were genotyped at and around the G72/G30 locus, which covered a 157-kb region encompassing the entire complementary DNA sequences of G72 and G30. We performed transmission/disequilibrium testing (TDT) and haplotype analysis, since a linkage-disequilibrium block was present at this gene locus. In the CNG and NIMH data sets, the results of global TDT of the entire haplotype set were significant and consistent (P=.0004 and P=.008, respectively). In the CNG series, the associated genotypes divided the families into those with linkage and those without linkage (partitioned by the linkage evidence). Analysis of the decay of haplotype sharing gave a location estimate that included G72/G30 in its 95% confidence interval. Although statistically significant association was not detected for individual SNPs in the NIMH data set, the same haplotype was consistently overtransmitted in both series. These data suggest that a susceptibility variant for bipolar illness exists in the vicinity of the G72/G30 genes. Taken together with the earlier report, this is the first demonstration of a novel gene(s), discovered through a positional approach, independently associated with both bipolar illness and schizophrenia.

Alternative Splicing↗

PubMed2002

Physical and transcript map of the hereditary prostate cancer region at xq27.

We have recently mapped a locus for hereditary prostate cancer (termed HPCX) to the long arm of the X chromosome (Xq25-q27) through a genome-wide linkage study. Here we report the construction of an approximately 9-Mb sequence-ready bacterial clone contig map of Xq26.3-q27.3. The contig was constructed by screening BAC/PAC libraries with markers spaced at approximately 85-kb intervals. We identified overlapping clones by end-sequencing framework clones to generate 407 new sequence-tagged sites, followed by PCR verification of overlaps. Contig assembly was based on clone restriction fingerprinting and the landmark information. We identified a minimal overlap contig for genomic sequencing, which has yielded 7.7 Mb of finished sequence and 1.5 Mb of draft sequence. The transcriptional mapping effort localized 57 known and predicted genes by database searching, STS content mapping, and sequencing, followed by sequence annotation. These transcriptional units represent candidate genes for HPCX and multiple other hereditary diseases at Xq26.3-q27.3.

Chromosome Mapping↗

PubMed1998

Expression of the CB1 cannabinoid receptor in macrophage-like cells from brain tissue: immunochemical characterization by fusion protein antibodies.

Antibodies designed to recognize a 74 amino acid sequence of the N- or C-terminal domain of the rat CB1 cannabinoid receptor detected a 58 kDa protein in immunoblots of brain and various cells known to express the CB1 cannabinoid receptor. A human B-lymphoblastoid cell line and macrophage-like cells from neonatal rat brain were also positive for CB1 receptor-like immunoreactivity. Immunocytochemical analysis performed with isolated Fab fragments showed surface staining in NG108-15 cells and brain macrophage like cells which also express MHC class II antigens. The data suggest a plausible role for CB1 receptors in the immune function of brain.

Animals↗