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P Deloukas

Publications and source records attributed to P Deloukas.

31 records · Page 2Linked to original sources
PubMed1998

Localization of HuC (ELAVL3) to chromosome 19p13.2 by fluorescence in situ hybridization utilizing a novel tyramide labeling technique.

HuC is a neural-specific member of the Elav family of RNA-binding proteins. This highly conserved gene family plays a crucial role in neurogenesis, and HuC (HGMW-approved symbol ELAVL3) is expressed at an early stage of neural development. Using a novel tyramide fluorescence in situ hybridization (T-FISH) technique, we localized HuC to chromosome 19p13.2. This localization was confirmed by radiation hybrid mapping and coincides with that of HuR (HGMW-approved symbol ELAVL1), another elav family member. Dual T-FISH analysis with HuC and HuR probes, however, indicated distinct loci, with HuC being centromeric to HuR. This study demonstrates the utility of T-FISH in colocalizing two genes on the same chromosomal preparation using only biotinylated probes.

Antigens, Surface↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

A detailed physical and transcriptional map of the region of chromosome 20 that is deleted in myeloproliferative disorders and refinement of the common deleted region.

Acquired deletions of the long arm of chromosome 20 are the most common chromosomal abnormality seen in polycythemia vera and are also associated with other myeloid malignancies. Such deletions are believed to mark the site of one or more tumor suppressor genes, loss of which perturbs normal hematopoiesis. A common deleted region (CDR) has previously been identified on 20q. We have now constructed the most detailed physical map of this region to date--a YAC contig that encompasses the entire CDR and spans 23 cM (11 Mb). This contig contains 140 DNA markers and 65 unique expressed sequences. Our data represent a first step toward a complete transcriptional map of the CDR. The high marker density within the physical map permitted two complementary approaches to reducing the size of the CDR. Microsatellite PCR refined the centromeric boundary of the CDR to D20S465 and was used to search for homozygous deletions in 28 patients using 32 markers. No such deletions were detected. Genetic changes on the remaining chromosome 20 may therefore be too small to be detected or may occur in a subpopulation of cells.

Centromere↗
PubMed1998

Z extensions to the RHMAPPER package.

MOTIVATION: Extensions have been made to the RHMAPPER-1.1 package. One set of extensions computes the totally linked markers and uses the results as input to the salient RHMAPPER functions. The second set of extensions uses TKperl to provide an interactive interface for ease of querying the database and displaying maps. AVAILABILITY: The extensions can be obtained via ftp.sanger.ac.uk/pub/zmapper. SUPPLEMENTARY INFORMATION: The User's Manual can be viewed from http:/www.sanger.ac.uk/Users/cari/Z.shtml. CONTACT: cari@sanger.ac.uk

Animals↗
PubMed1996

Physical mapping of chromosome 6: a strategy for the rapid generation of sequence-ready contigs.

The development of radiation hybrid (RH) mapping (Cox et al., 1990) and the availability of large numbers of STS markers, together with extensive bacterial clone resources provided a means to accelerate the process of mapping a human chromosome and preparing bacterial clone contigs ready to sequence. Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. We report here a strategy which initially involves establishing a high density framework map using RH mapping. The framework markers are then used for the identification of bacterial genomic clones covering the chromosome. The bacterial clones are analysed by restriction enzyme fingerprinting and STS-content analysis to identify sequence-ready contigs. Contig gap closure will also be performed by clone walking.

Chromosome Mapping↗
PubMed1995

The complete exon-intron structure of the 156-kb human gene NFKB1, which encodes the p105 and p50 proteins of transcription factors NF-kappa B and I kappa B-gamma: implications for NF-kappa B-mediated signal transduction.

The NFKB1 gene encodes three proteins of the NF-kappa B/Rel and I kappa B families: p105, p50, and (in mouse) I kappa B-gamma. We determined the complete genomic structure of human NFKB1. NFKB1 spans 156 kb and has 24 exons with introns varying between 40,000 and 323 bp in length. Although NFKB2, which encodes p100 and p52, also has 24 exons and has a comparable exon-intron structure, it is 20 times shorter (8 kb; Fracchiola et al. (1993) Oncogene 8, 2839-2845) than NFKB1. We propose that the long size of NFKB1 is important for transient activation of NF-kappa B complexes containing p50. I kappa B-gamma corresponds to the carboxyl-terminal half of p105. DNA sequence analysis showed that the 3'-end of human intron 11 and the 5'-end of exon 12 of NFKB1 are colinear with the 5'-untranslated region of mouse I kappa B-gamma cDNA. I kappa B-gamma is thus likely to be generated by transcription starting within intron 11 and not by alternative splicing of the mouse mRNA encoding p105 and p50.

Amino Acid Sequence↗
PubMed1994

The human NFKB3 gene encoding the p65 subunit of transcription factor NF-kappa B is located on chromosome 11q12.

A YAC clone that contains the human gene NFKB3, encoding the p65 subunit of transcription factor nuclear factor kappa B (NF-kappa B), was isolated. The YAC contains the entire NFKB3 gene, which is smaller than 15 kb and present in a single copy in the genome. Fluorescence in situ hybridization with metaphase chromosomes showed two different chromosomal locations (11q12 and Xp11.4) for sequences present in the YAC. The NFKB3 gene was assigned to chromosome 11q12 by PCR analysis of a panel of relevant hybrid cell lines. Thus, no linkage exists between NFKB3 and genes encoding other known members of the NF-kappa B family.

Base Sequence↗
PubMed1993

Three human glutamate dehydrogenase genes (GLUD1, GLUDP2, and GLUDP3) are located on chromosome 10q, but are not closely physically linked.

Yeast artificial chromosomes (YACs) of 340 and 370 kb that contain the functional human glutamate dehydrogenase gene (GLUD1) and the pseudogene GLUDP2, respectively, were isolated. These genes were not physically linked to each other nor to any other sequences homologous to the exons of GLUD1. No additional GLUD sequences were found within at least 70 kb of the 5' and 175 kb of the 3' end of GLUD1 or 150 kb of either end of GLUDP2. By in situ hybridization, GLUD1 was located at 10q23.3, GLUDP2 at 10q11.2, and another pseudogene of the GLUD gene family, GLUDP3, at 10q22.1. DNA fragments of these three genes showed cross-hybridization to the loci assigned to the other two genes, but not to any other chromosomal locus. Thus, these three genes are located at distinct positions on chromosome 10q.

Base Sequence↗
PubMed1993

Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing.

Transcription factor NF-kappa B represents a family of closely related homo- and heterodimeric factors. The most abundant form of NF-kappa B is the p50/p65 heterodimer. We determined the complete genomic structure of the human gene and a partial structure of the mouse gene encoding p65. The human gene consists of ten exons and spans about 8.1 kbp of DNA. The exon-intron organization in the rel homology domain (exons 2 to 7) is conserved when compared to human and turkey c-rel, strengthening the evolutionary relationship between p65 and c-rel. The lengths of the corresponding introns 5 and 6 in the human and mouse p65 genes are not conserved. However, a surprisingly high degree of conservation of intron sequences was observed between both species. We show that the naturally occurring shorter variant of p65 (p65 delta) can be generated by alternative splicing of intron 6, not only in humans but also in mouse. In addition, the existence of another, as yet unknown splice variant of p65 is predicted.

Alternative Splicing↗
PubMed1992

Construction of yeast artificial chromosome (YAC) clone banks covering three genome equivalents and isolation of YACs containing the human gene encoding tumor necrosis factor receptor beta.

Yeast artificial chromosome (YAC) banks covering in total about three haploid genome equivalents were constructed using a human Epstein-Barr-virus-transformed B lymphocytic cell line. Two clone banks were made: 20,000 clones with average inserts of 350 kb in the pYAC4 vector and 9850 clones with average inserts of 180 kb using vectors pJS89 and pJS91. Direct comparison of pYAC4 with pJS89 and pJS91 showed pYAC4 to be the most suitable cloning vector. Two partial banks with average insert sizes of 220 kb for human endothelial cell DNA and epithelial HEp2 cell DNA were also constructed, each covering 10% of the haploid genome. A rapid, three-step PCR screening procedure for isolation of individual YAC clones was developed and used to identify two clones encoding TNF-R beta. These clones cover about 200 kb and have 170 kb in common. TNF-R beta is 9.3 kb long and contains two introns within the protein-coding sequence.

Base Sequence↗
PubMedDate not supplied

The DNA sequence and comparative analysis of human chromosome 20.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Animals↗