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- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 2. |
- Hazenkamp-Von Arx, M.E., et al.
(författare)
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PM2.5 and NO2 assessment in 21 European study centres of ECRHS II : annual means and seasonal differences
- 2004
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Ingår i: Atmospheric Environment. - : Elsevier. - 1352-2310 .- 1873-2844. ; 38:13, s. 1943-1953
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Tidskriftsartikel (refereegranskat)abstract
- The follow-up of cohorts of adults from more than 20 European centres of the former ECRHS I (1989-1992) investigates long-term effects of exposure to ambient air pollution on respiratory health, in particular asthma and change of pulmonary function. Since PM2.5 is not routinely monitored in Europe, we measured PM2.5 concentrations in 21 participating centres to estimate 'background' exposure in these cities. Winter (November-February), summer (May-August) and annual mean (all months) values of PM2.5 were determined from measuring periods between June 2000 and November 2001. Sampling was conducted for 7 days per month for a year. Annual and winter mean concentrations of PM2.5 vary substantially being lowest in Iceland and highest in centres in Northern Italy. Annual mean concentrations ranged from 3.7 to 44.9 mug m(-3), winter mean concentrations from 4.8 to 69.2 mug m(-3), and summer mean concentrations from 3.3 to 23.1 mugm(-3). Seasonal variability occurred but did not follow the same pattern across all centres. Therefore, ranking of centres varied from summer to winter. Simultaneously, NO2 concentrations were measured using passive sampling tubes. Annual mean NO2 concentrations range from 4.9 to 72.1 mug m(-3) with similar seasonal variations across centres and constant ranking of centres between seasons. The correlation between annual NO2 and PM2.5 concentrations is fair (Spearman correlation coefficient r(s) = 0.75), but when considered as monthly means the correlation is far less consistent and varies substantially between centres. The range of PM2.5 mass concentrations obtained in ECRHS II is larger than in other current cohort studies on long-term effects of air pollution. This substantial variation in PM2.5 exposure will improve statistical power in future multilevel health analyses and to some degree may compensate for the lack of information on within-city variability. Seasonal means may be used to indicate potential differences in the toxicity across the year. Across ECRHS cities annual NO2 might serve as a surrogate for PM2.5, especially for past exposure assessment, when PM2.5 is not available.
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