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K Gardiner

Publications and source records attributed to K Gardiner.

At least 19 recordsLinked to original sources
PubMed1998

Molecular cloning of a human cDNA IGSF3 encoding an immunoglobulin-like membrane protein: expression and mapping to chromosome band 1p13.

We report the isolation and characterization of a novel cDNA IGSF3 that contains a 3648-bp open reading frame encoding an apparent immunoglobulin (Ig)-like membrane protein characterized by eight Ig domains. IGSF3 has an overall structural similarity and strong sequence similarity to V7, a human leukocyte surface protein. The IGSF3 mRNA is highly expressed in placenta, kidney, and lung, but is also present in a wide range of other human tissues. Although a small internal sequence of the IGSF3 cDNA hybridizes to a YAC derived from the centromeric region of chromosome 21, in situ hybridization experiments on human metaphase chromosomes show that the gene corresponding to the long cDNA that we cloned is located in chromosome band 1p13 and that related sequences are located on chromosomes 2 and 13. These data serve to emphasize the potential difficulties in transcriptional mapping in centromeric regions.

Amino Acid Sequence↗
PubMed1998

Analysis of pufferfish homologues of the AT-rich human APP gene.

Mutations in the beta-amyloid precursor protein (APP) gene are associated with some forms of Familial Alzheimer's Disease. The human APP gene is large, the 19 exons span approximately 300 kb, and AT-rich, at 40% GC. We have examined the genomic structure and cDNA sequence of the APP gene in the pufferfish Fugu rubripes and Tetraodon fluviatilis, respectively. In contrast to human, the Fugu APP gene spans less than 10 kb of DNA, with the introns compacted 48-fold on average. Two axons, alternatively processed in humans, are absent in both pufferfish. APP is the largest, most AT-rich gene examined in Fugu and is also the most highly compressed. The genomic sequences spanning the human and the Fugu APP genes were analysed with a set of exon and gene prediction programs. Results show that these are highly reliable for the Fugu gene with lower false positive and false negative rates than are seen in the analysis of the human gene. Comparative analysis of Fugu sequences homologous to very AT-rich regions in the human genome may, therefore, be advantageous in gene-finding efforts, both for their highly reduced sizes and their reliable gene predictions.

Alzheimer Disease↗
PubMed1998

Occupational urothelial tumours: a regional case-control study.

OBJECTIVE: To investigate the role of occupational exposures in the risk of developing urothelial cancer. MATERIALS AND METHODS: Occupational histories, obtained using a self-administered questionnaire, for 803 patients with urothelial cancer (first diagnosed 1991-93) were compared with similar information for 2135 matched controls. Relative risks (RRs) were estimated using conditional logistic regression. Comparisons were also made with historical regional employment information available from the 1971 census. RESULTS: There were many statistically significant positive associations for urothelial cancer risks and ever being employed in specified occupations (with or without statistical adjustment for smoking status in 1991). Smoking-adjusted RRs of > 2.0 were obtained for seven occupations; manufacture of fire lighters/ patent fuels (RR 4.30, 95% confidence interval 0.78-23.79), rodent extermination (3.71, 1.20-11.48), manufacture of dyestuffs (2.61, 0.98-7.00), leather work (2.51, 1.44-4.35), cable manufacturing industry (2.46, 1.20-5.04), textile printing and dyeing (2.32, 0.98-5.45), and sewage works (2.19, 1.16-4.11). Analyses of the occupations followed in 1971 (thus allowing for 20-year latency) indicated an elevated RR for workers in the plastics industry (5.22, 1.57-17.36). CONCLUSIONS: The historical legacy of exposure to aromatic amines in the rubber, cable-making, dyestuffs and other industries remains. An important proportion of patients presenting with urothelial tumours are likely to have had occupational exposure to urothelial carcinogens. A review of occupational exposures in the contemporaneous plastic, textile and leather industries is warranted.

Adult↗
PubMed1997

Clonability and gene distribution on human chromosome 21: reflections of junk DNA content?

Data from transcriptional mapping of human chromosome 21 have been compiled from a number of sources. Regardless of the gene identification technique used, a consistent picture has developed: the centromere proximal half of 21q, which contains 50% of the DNA (20 Mb), harbors only 10% of the expressed sequences. Because of the variety of gene isolation techniques used, this result is unlikely to arise simply from methodological artefacts, biases in clonability or tissue specificity of expression. This region is known to be AT-rich and to contain APP, the largest gene (spanning 300 kb) currently analyzed on 21q. Interesting preliminary data from analysis of the Fugu rubripes homolog of APP has shown an unusually high, 50-fold, compaction of intron size, raising the intriguing possibility that >90% of the DNA in the human gene may be functionless. Thus, data from a variety of approaches suggest that a large part of 21q very likely has neither coding capacity nor associated regulatory function. By these criteria, it is a good candidate for a repository of junk DNA.

Animals↗
PubMed1997

Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia.

We have identified a novel gene, GR6, located within the leukemia breakpoint region of 3q21, that is normally expressed in early fetal development but not in adult peripheral blood. GR6 is activated in the UCSD-AML1 cell line and in a leukemic sample, both of which carry a t(3;3)(q21;q26). In UCSD-AML1, we have also identified fusion transcripts between the ecotropic viral insertion site I (EVI1) gene in 3q26 and GR6 and between EVI1 and Ribophorin I that maps 30 kb telomeric to GR6 in 3q21. All fusions splice the 5' ends of the 3q21 genes into exon 2 of the EVI1 gene, an event that is similar to the normal intergenic splicing of MDS1-EVI1 and to those previously documented in leukemias with t(3;21) and t(3;12), in which acute myelogenous leukemia 1-EVI1 fusions and ETV6-EVI1 fusions, respectively, occur. The Ribophorin I-EVI1 fusion in particular may be a common occurrence in t(3;3).

Adult↗
PubMed1997

Leukemia breakpoint region in 3q21 is gene rich.

Rearrangements of the long arm of human chromosome 3, including reciprocal translocations, inversions and deletion/duplication of bands 3q21-3q26, as well as deletions of 3q21 and reciprocal translocations between 3q21 and other chromosomes, are well documented in leukemia. Previous studies showed that the breakpoints within 3q21 cluster within a 10-40 kb region but no candidate genes were described. In this work, we have identified partial cDNAs corresponding to five to nine new transcripts from an 80 kb P1 clone that spans ten breakpoints. These transcripts, with one exception, appear to be expressed only at low levels in the set of cancer cell lines examined. Four transcripts are located between the previously mapped Ribophorin I gene and the most centromeric breakpoint; three map directly within the 20 kb spanning nine independent breakpoints. These data (i) show that among characterized leukemia breakpoint regions 3q21 is unusually gene rich, (ii) provide new candidates for relevance to leukemia in 3q21, and (iii) suggest possibilities for chromatin configuration effects.

Chromosome Breakage↗
PubMed1997

Map location, genomic organization and expression patterns of the human RED1 RNA editase.

A cDNA fragment containing sequences homologous to the rat RED1 RNA editase gene was recently identified on human chromosome 21. Here we report the location of this cDNA in distal 21q22.3 near the CD18 gene. We also report isolation of cDNA clones containing the complete coding region of the human RED1 gene, and use of this sequence to determine the genomic structure from overlapping cosmids. Human RED1 spans approximately 25 kb and is composed of 10 exons containing coding sequences. The two RNA binding domains are located within a single large, 935 nucleotide, exon 2. An alternatively processed exon 6 potentially interrupts the catalytic domain. Exon 10 is largely composed of the 3' untranslated region, which is unusually high in GC content and contains a segment that is > 90% identical with the 3' UT of the homologous rat gene. A survey of expression patterns reveals differential processing of the 5 and 8.5 kb transcripts in all sources examined. The difference in transcript size likely results from alternative processing in the 3' UT. Potential relevance of overexpression of RED1 to the development of the Down Syndrome phenotype is discussed.

Adenosine Deaminase↗
PubMed1997

Efficiency of different grouping schemes for dust exposure in the European carbon black respiratory morbidity study.

OBJECTIVES: The aim of this study was to assess the theoretical efficiencies of different grouping strategies and its effect on the exposure-response relation in a study of respiratory morbidity associated with exposure to total inhalable and respirable carbon black dust. METHODS: A large epidemiological study is being undertaken to investigate the respiratory health of employees in the European carbon black manufacturing industry in relation to exposure to carbon black dust. In phase 2 of the study, repeated measurements of total inhalable and respirable dust were taken which enabled estimation of various components of variability in the exposure data (within and between worker variance and within and between group variance). These variance components were used to calculate the contrast in exposure between the groups in various classification schemes and to calculate the theoretical attenuation of the exposure-response relation and the standard error (SE) of the slope. RESULTS: High contrast in exposure was found when workers were classified according to the combination of their factory and job category as well as when these combinations were amalgamated into five exposure groups. Attenuation was minimal with most grouping schemes; only with the individual based strategy was the attenuation large. The SE of the theoretically attenuated exposure-response slope was smallest for the strategy based on individual people followed by the classification scheme based on factory and job category. CONCLUSIONS: It was concluded that, although some assumptions for the calculations of the attenuation of the exposure-response slope were not met, the most appropriate classification scheme of the worker seems to be by the combination of factory and job category.

Carbon↗
PubMed1996

Molecular genetic characterization and comparative mapping of the human PCP4 gene.

The mouse Pcp4 gene is highly expressed in brain, primarily in cerebellar Purkinje cells. It maps to chromosome 16 (Chr 16), in a region of conserved synteny with human chromosome 21 (Chr 21). To further characterize PCP4 and its possible contribution to cerebellar hypoplasia in trisomy 21, or Down Syndrome (DS), we cloned and sequenced the full length human cDNA, isolated a YAC which carries the entire gene, determined the gene structure, and characterized its expression. The gene spans at least 55 kb and contains two introns, the placement of which is the same in mouse. Expression in the mouse brain during development was detected at embryonic day 10, and thereafter through development. The PCP4 YAC was placed on the human Chr 21 YAC contig by a link to a YAC carrying the markers D21S15 and D21S349. This placement distal to ETS2 was confirmed by mapping on a somatic cell hybrid panel of Chr 21 translocations. This position caused an apparent break in gene order with mouse Chr 16. However, mapping in the mouse was reassessed, and Pcp4 and a linked marker, D16Mit71, were both moved distal to Ets2, corresponding to the position of PCP4 on Chr 21.

Amino Acid Sequence↗
PubMed1996

Occupational exposure to carbon black in its manufacture: data from 1987 to 1992.

Carbon black is a very pure form of very finely divided particulate carbon used mainly in the automotive tyre industry. Its carbonaceous nature and submicron size (unpelleted) have raised concerns with regard to its ability to affect respiratory morbidity. This paper describes the exposure to carbon black dust in the first and second phase of a large multi-national epidemiological study investigating the magnitude of these exposure-related effects. In Phase I, 1278 respirable dust samples were taken (SIMPEDS cyclone) which increased to 2941 in Phase II with a similar rise in the number of total inhalable dust samples (IOM head) from 1288 in Phase I to 3433 Phase II. Exposure dropped markedly between the two phases with total inhalable dust showing a bigger reduction (49.9%) than respirable dust (42%), although the mean exposure for certain factories and job categories dropped more than others. The data are presented by the 14 job titles/numbers (21-34). The highest mean exposure in both phases and for both dust fractions is experienced by the warehouse packers and they are also most likely to exceed the OES of 3.5 mg m-3 (35.1% of samples in Phase I and 12.0% in Phase II).

Air Pollutants, Occupational↗
PubMed1996

Base composition and gene distribution: critical patterns in mammalian genome organization.

Recent success in developing transcriptional maps of large genomic regions provide excellent opportunities for the investigation of mammalian genome organization. Detailed definition of organizational features will, in the short term, aid in prioritizing genomic sequencing efforts and in interpreting sequencing results and, in the long term, will surely provide insights into the structural, functional and evolutionary basis for the mammalian chromosome and chromosomal banding patterns. For such efforts, human chromosome 21 provides an excellent model system because the physical and clone maps are detailed, and several transcriptional mapping projects have provided large numbers of novel genes. It is, therefore, valuable at this point to examine these transcriptional mapping data and to compare them with the isochore model of the mammalian genome, which describes patterns in base composition and predicts gene distributions. Not only do compelling organizational patterns appear, but new questions about additional possible patterns in gene size, structure, conservation and transcription can be asked.

Animals↗
PubMed1996

Integration of 30 CA-repeat markers into the cytogenetic, genetic and YAC maps of human chromosome 21.

The number of polymorphic DNA markers developed for the whole human genome during the last 2 years has been vastly increased. For this reason, the genetic map is continuously improving, but the cytogenetic and physical maps are not progressing at the same speed. Therefore, there is a need to integrate genetic, cytogenetic and physical mapping data. We have developed and localized on the breakpoint map of human chromosome 21 thirty microsatellite markers. Twenty of them have been used in the construction of a genetic map of chromosome 21, which contains a total of 44 markers. This map has 39 uniquely placed loci at 23 anchor points, ordered with odds of at least 1,000:1. The sex average length of the map is 64.4 cM, with the male and female lengths being 49.4 and 79.2 cM, respectively. Twenty-six of these newly developed markers have been localised on the CEPH/Généthon and Joint YAC Screening Effort YACs. Although these microsatellites were found uniformly spread along chromosome 21, the detection of various markers in the same or adjacent YACs suggests that CA-repeat microsatellites are clustered in several regions. The localization of these markers on the cytogenetic, genetic and YAC maps has provided a refined location for them and is a step further towards the construction of an integrated map of HC21.

Chromosome Mapping↗
PubMed1995

Localization of cDNAs to a region poorly represented in the CEPH chromosome 21 YAC contig: candidate genes for genetic diseases mapped to 21q22.3.

Fifty-three cDNA fragments previously obtained by hybridization selection from random clones in the chromosome 21 cosmid library LL21CNO2 failed to identify clones in the chromosome 21 YAC contig described by Chumakov et al. (1992, Nature 359: 380-387). Using an expanded panel of somatic cell hybrids, we have verified that the majority of these cDNAs map to chromosome 21 and that in particular a very high proportion, approximately 85%, localize to a 5-Mb region of distal 21q22.3. Pulsed-field analysis coupled with information from the NotI restriction map of the region further indicate that 17 cDNA fragments map within 650 kb of the PFKL gene and thus may be candidates for genetic diseases linked to this gene. This work helps to characterize a region poorly represented in the CEPH YAC contig and adds to the number of cDNAs useful in analysis of chromosome 21-associated diseases.

Animals↗