Search PubMed⌕ Search

Biomedical subjects

G Lennon

Publications and source records attributed to G Lennon.

At least 19 recordsLinked to original sources

Molecular characterisation and analysis of bovine rotavirus strains circulating in Ireland 2002-2004.

One hundred and two faecal samples were collected from calves diagnosed with rotavirus infection, in the southern region of Ireland, from 2002 to 2004. Ninety one percent (n=93) were confirmed positive for rotavirus, using latex agglutination and enzyme linked immunosorbent assay (ELISA) methods. Determination of the G- and P-types was carried out using nested reverse transcriptase polymerase chain reaction (nRT-PCR). G6 was the most prevalent genotype, accounting for 80.6% (75/93), G10 accounted for 6.5% (6/93) and G6G10 mixed types accounted for 9.7% (9/93) of the collection. Rotavirus in three of the samples (3.2%) could not be characterised with any of the five G-specific primers used in this study. A subset of the positive samples (n=54) was examined for their P-type specificities, P[5] and P[11] accounted for 77.8% (42/54), and 9.3% (5/54), respectively. One P[1] genotype (1.9%) was found in the collection. P[5] and P[11] mixed genotypes accounted for 11% (6/54) of the study. The genotypes corresponded to the UK-like strain (G6P[5]) 57.4%, KN4-like strain (G6[P11]) 7.4%, B223-like strain (G10P[11]) and NCDV-like strain (G6P[1]) 1.9% each. The unusual combination of G10P[5] accounted for 7.4%, with mixed infections G6+G10P[5] and G6P[5]+P[11] representing 13% and 11%, respectively. This is the first time that the G- and P-types of bovine rotaviruses (BRVs) have been determined in Ireland, and this study contributes to a better understanding of the epidemiology of such viruses circulating in Ireland.

Animals↗

Joseph-Frédéric-Benoît Charrière: master cutler and instrument designer.

Modern surgery owes its development to the innovations and skill of those craftsmen in the early 19th Century. Joseph-Frédéric-Benoît Charrière was a Parisian Cutler of renowned fame. He pioneered many developments in ether administration, urologic and other general surgical instrumentation. He also made profound modifications to the syringe, haemostat and aneurysm clip. Charrière, most importantly, developed the French (Fr) or Charrière (Ch) gauge system used in sizing catheters and endoscopic equipment (1 Charr. = 0.333 mm). His contributions were widespread and are still evident today.

Anesthesia↗

Reproducible gene expression measurement among multiple laboratories obtained in a blinded study using standardized RT (StaRT)-PCR.

BACKGROUND: A method that provides standardized data and is relatively inexpensive and capable of high throughput is a prerequisite to the development of a meaningful gene expression database suitable for conducting multi-institutional clinical studies based on expression measurement. Standardized RT (StaRT)-PCR has all these characteristics. In addition, the method must be reproducible. StaRT-PCR has high intralaboratory reproducibility. The purpose of this study is to determine whether StaRT-PCR provides similar interlaboratory reproducibility. METHODS AND RESULTS: In a blinded interlaboratory study, expression of ten genes was measured by StaRT-PCR in a complementary DNA sample provided to each of four laboratories. The average coefficient of variation for interlaboratory comparison of the nine quantifiable genes was 0.48. In all laboratories, expression of one of the genes was too low to be measured. CONCLUSION: Because StaRT-PCR data are standardized and numerical and the method is reproducible among multiple laboratories, it will allow development of a meaningful gene expression database.

Binding, Competitive↗

A transcript map of a 10-Mb region of chromosome 19: a source of genes for human disorders, including candidates for genes involved in asthma, heart defects, and eye development.

Several projects have produced maps of the physical position of genes within the human genome, either on a genome-wide scale or of a more detailed subsection of a chromosome. However, these maps largely rely on the mapping of expressed sequences (cDNAs and ESTs) back onto physical maps by their localization onto specific fragments of DNA within the radiation hybrid panels. In this report we present a gene map of a section of chromosome 19 that has been derived by combining the use of a method of gene identification (exon trapping) that does not rely on expression patterns, with data available in the genome databases to produce a fine-detailed transcript map. This map also provides several potential candidates for disorders that map to this region of the genome. Details of the maps and more detailed descriptions of cosmid contigs, exon sequences, and expression patterns for the 96 exons that form the basis of this transcript map are available on a series of Web pages that are referenced in this report. These Web pages can be accessed from http://www.nottingham.ac.uk/ pdzmgh/tm/livemap19q. html.

Asthma↗

A new zinc ribbon gene (ZNRD1) is cloned from the human MHC class I region.

Eleven unique cDNA fragments were identified from YAC B30H3, which spans 330 kb in the human major histocompatibility complex class I region. One fragment (CAT80) was mapped 80 kb telomeric to the HLA-A locus. Using this cDNA fragment as probe, Northern analysis reveals a ubiquitously expressed transcript of about 850 nt in all 16 tissues tested. Based on the cDNA fragment sequence, a full-length cDNA of 858 bp that contains an open reading frame of 378 bp was cloned. Within the putative polypeptide of 126 amino acids, two zinc-ribbon domains were identified: Cx2Cx15Cx2C at the N-terminal and Cx2Cx24Cx2C at the C-terminal. The C-terminal domain is well conserved throughout evolution, including archaea, yeast, Drosophila, nematodes, amphibians, and mammals. The conserved amino acid sequence, CxRCx6Yx3QxRSADEx2TxFxCx2C, is highly homologous to the yeast RNA polymerase A subunit 9 and transcription-associated proteins. Alignment with genomic DNA demonstrates that this gene spans 3.6 kb and consists of four exons and three introns. Cross-species Northern analysis reveals a mouse homolog of a similar size and with an expression profile similar to those of the human gene. We have named this gene ZNRD1 for zinc ribbon domain-containing 1 protein.

Amino Acid Sequence↗

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗

IMAGEne I: clustering and ranking of I.M.A.G.E. cDNA clones corresponding to known genes.

MOTIVATION: To enhance the usefulness of the I.M.A.G.E. Consortium (Lennon et al., 1996, Genomics, 33, 151-152) cDNA clone collection by directed analysis and organization of their associated Expressed Sequence Tags (ESTs), thus enabling effective mining of the immense amounts of public cDNA information. RESULTS: This paper introduces the IMAGEne suite of tools, which clusters ESTs around known genes, then ranks each clone within a cluster. IMAGEne filters data from known gene sequence databases and the GenBank's EST database (Boguski and Shuler, 1995, Nature Genet., 10, 369-371). It applies biological criteria in connection with judicious use of the BLAST (Altschul et al., 1990, J. Mol. Biol., 215), FASTA (Pearson and Lipman, 1988, Proc. Natl Acad. Sci. USA, 85, 2444-2448; Pearson, 1990, Methods Enzymol., 183, 63-98; Gusfield, 1997, Algorithms on Strings, Trees, and Sequences, Cambridge University Press), and SIM (Huang et al., 1990, Comput. Appl. Biosci., 6, 373-381) tools to form known gene clusters. It then applies criteria derived from experienced biologists to select the best representative I.M.A.G.E. clone for a gene. The tool provides an intuitive Java interface for query and display of the gene and its associated clones, thus directing researchers in selecting a clone that will best enhance their research. An important product is a listing of clones that best represent all known genes. The listing will be used for re-arraying clones into minimally redundant Master Arrays. Both the listings and Master Arrays will be made available to the public, which will be a valuable resource to the genomic community in furthering discovery in the area of gene function.

Algorithms↗

Human endopeptidase 24.15 (THOP1) is localized on chromosome 19p13.3 and is excluded from the linkage region for late-onset Alzheimer disease.

The mapping position of human endopeptidase 24.15 (THOP1) has previously been reported to be within the linkage region for the late-onset Alzheimer disease AD2 locus on chromosome 19q13.3. After localizing THOP1 to the high-resolution cosmid contig map of human chromosome 19, we found that the previous report was incorrect. Results of the hybridization and FISH mapping of positive clones indicated localization of THOP1 to chromosome 19p13.3 and not 19q13. 3. This localization is a correction of wrong chromosomal delegation and excludes THOP1 from the region that shows evidence of linkage to late-onset familial Alzheimer disease.

Alzheimer Disease↗

High-resolution mapping of ribosomal protein genes to human chromosome 19.

In a systematic effort for mapping of all the human ribosomal protein (rp) genes, we have found that an unusually large number (12) of rp genes are present on chromosome 19 and subsequently determined their locations on the chromosome by a radiation-hybrid procedure. For this, we isolated cosmid clones corresponding to each gene and placed nine of them on a metric physical map of chromosome 19. Although most genes are scattered over the chromosome, we found three genes are clustered in a 0.6-Mb region at 19q13.3 and two of them, RPL13A and RPS11, within a single cosmid only 4.3 kb apart. To explore a possible relationship between rp gene defects and human disease, we compared map positions of the rp genes and disease loci on chromosome 19, which led us to find RPS9 gene in the same interval as the gene for retinitis pigmentosa 11. The disease locus has previously been mapped to the 6-cM interval at 19q13.4 between markers D19S572 and D19S926, which corresponds to less than 2-Mb region on the metric physical map. We mapped RPS9 about 800 kb distal to D19S572.

Base Sequence↗

Localization and genomic structure of human deoxyhypusine synthase gene on chromosome 19p13.2-distal 19p13.1.

The amino acid hypusine is formed post-translationally in a single cellular protein, the eukaryotic translation initiation factor 5A, by two enzymes, namely deoxyhypusine synthase and deoxyhypusine hydroxylase. Hypusine is found in all eukaryotes and in some archaebacteria, but not in eubacteria. The deoxyhypusine synthase cDNA was cloned and mapped by fluorescence in situ hybridization on chromosome 19p13.11-p13.12. Rare cDNAs containing internal deletions were also found. We localized the deoxyhypusine synthase gene on a high resolution cosmid/BAC contig map of chromosome 19 to a region in 19p13.2-distal 19p13.1 between MANB and JUNB. Analysis of the genomic exon/intron structure of the gene coding region showed that it consists of nine exons and spans a length of 6.6kb. From observation of the genomic structure, it seems likely that the internally deleted forms of mature RNA are the result of alternative splicing, rather than of artifacts.

Alternative Splicing↗

CAG/CTG and CGG/GCC repeats in human brain reference cDNAs: outcome in searching for new dynamic mutations.

CAG and CGG expansion is associated with 10 inherited neurological diseases and is thought to be involved in other human genetic diseases. To identify new candidate genes, we have undertaken a large-scale screening project for CAG/CTG ([CAG]n) and CGG/GCC ([CGG]n) repeats in human brain reference cDNAs. Here, we present the final classification for 597 cDNAs selected by CAG and CGG hybridization from two libraries (100,128 clones) and the updated characterization of [CAG]n- and [CGG]n-positive cDNAs (repeat polymorphism and cDNA localization). We have selected 124 CAG and 83 CGG hybridization-positive clones representing new genes, from which 49 CAG and 7 CGG repeats could be identified. New [CAG]n and [CGG]n with more than seven to nine units were rare (1/2000), and perfect [CAG]n 9 were more likely polymorphic. Overall, highly polymorphic to monomorphic new [CAG]n > 9 and [CGG]n > 7 were characterized. The comparison of our data with other [CAG]n and [CGG]n resources suggests that the screening of reference cDNAs leads to unique sources of new [CAG]n and [CGG]n and will enhance the study of enlarged triplet repeats in human genetic diseases.

Brain↗

Chromosomal localization and genomic structure of the human arsenite-stimulated ATPase (hASNA-I).

The hASNA-I is a novel human arsenite-stimulated ATPase identified as the human paralogue of the ATPase component of the arsenite efflux system in E. coli. The hASNA-I has distinct biochemical properties and a dual nuclear and cytoplasmic distribution. Immunohistochemical staining showed a distinct pattern of hASNA-I expression in cells within normal tissues, and its overexpression in breast cancer. Recently, the yeast two-hybrid system has identified hASNA-I as a cellular partner of metallothionein II suggesting an additional role in Zn homeostasis and cellular detoxification. This report describes the assignment of hASNA-I to human chromosome 19 by somatic-cell hybrid PCR mapping, the isolation of a chromosome 19-specific cosmid clone, and the genomic structure and exon-intron boundaries of hASNA-I. Our results indicate that the coding region of hASNA-I consists of 4 exons spanning 6 kb on band 19q13.3. These data will facilitate molecular analysis of the role of hASNA-I in human disease.

Adenosine Triphosphatases↗

Cloning, sequencing, gene organization, and localization of the human ribosomal protein RPL23A gene.

The intron-containing gene for human ribosomal protein RPL23A has been cloned, sequenced, and localized. The gene is approximately 4.0 kb in length and contains five exons and four introns. All splice sites exactly match the AG/GT consensus rule. The transcript is about 0.6 kb and is detected in all tissues examined. In adult tissues, the RPL23A transcript is dramatically more abundant in pancreas, skeletal muscle, and heart, while much less abundant in kidney, brain, placenta, lung, and liver. A full-length cDNA clone of 576 nt was identified, and the nucleotide sequence was found to match the exon sequence precisely. The open reading frame encodes a polypeptide of 156 amino acids, which is absolutely conserved with the rat RPL23A protein. In the 5' flanking region of the gene, a canonical TATA sequence and a defined CAAT box were found for the first time in a mammalian ribosomal protein gene. The intron-containing RPL23A gene was mapped to cytogenetic band 17q11 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Isolation of chromosome 18-specific brain transcripts as positional candidates for bipolar disorder.

Several studies have proposed the existence of susceptibility loci for bipolar disorder on chromosome 18. To identify possible candidate genes for this disease, we isolated brain-expressed transcripts by direct cDNA selection on chromosome 18-specific biotinylated cosmid clones. Longer cognate cDNA clones of the selected cDNAs were isolated from a normalized infant brain cDNA library. Physical mapping by PCR on a panel of somatic cell hybrids was conducted by the use of primers derived from partial sequences on either the 5' or 3' ends of the clones. In our initial analysis, 48 cDNA clones were found to be chromosome 18-specific, mapping to different subchromosomal regions. Sequence redundancy among these clones yielded 30 unique transcripts, five of which were represented in previously known genes. Further sequencing of the remaining 25 unique cDNA clones confirmed the absence of significant homology to known genes, indicating that these transcripts represented novel genes. Mapping with the use of a radiation hybrid panel positioned the brain cDNAs to within = 100 to 1100 kb from reference sequence tag sites (STSs) and assembled them into six high resolution linkage groups. The majority of the transcripts were found to cluster to discrete locations on 18p and 18q, previously hypothesized as susceptibility regions for bipolar disorder, identifying them as positional candidate genes.

Bipolar Disorder↗