Catalog Of Human Genes Research Articles

Diversity of Translation Start Sites May Define Increased Complexity of the Human Short ORFeome

Our previous proteomics analysis of small proteins expressed in human K562 cells provided the first direct evidence of translation of upstream ORFs in human full-length cDNAs (Oyama, M., Itagaki, C., Hata, H., Suzuki, Y., Izumi, T., Natsume, T., Isobe, T., and Sugano, S. (2004) Analysis of small human proteins reveals the translation of upstream open reading frames of mRNAs. Genome Res. 14, 2048-2052). In the present study, we performed an in-depth proteomics analysis of human K562 and HEK293 cells using a two-dimensional nano-liquid chromatography-tandem mass spectrometry system. The results led to the identification of eight protein-coding regions besides 197 small proteins with a theoretical mass less than 20 kDa that were already annotated coding sequences in the curated mRNA database. In addition to the upstream ORFs in the presumed 5'-untranslated regions of mRNAs, bioinformatics analysis based on accumulated 5'-end cDNA sequence data provided evidence of novel short coding regions that were likely to be translated from the upstream non-AUG start site or from the new short transcript variants generated by utilization of downstream alternative promoters. Protein expression analysis of the GRINL1A gene revealed that translation from the most upstream start site occurred on the minor alternative splicing transcript, whereas this initiation site was not utilized on the major mRNA, resulting in translation of the downstream ORF from the second initiation codon. These findings reveal a novel post-transcriptional system that can augment the human proteome via the alternative use of diverse translation start sites coupled with transcriptional regulation through alternative promoters or splicing, leading to increased complexity of short protein-coding regions defined by the human transcriptome.

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes

The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

KIDNEY GENE DATABASE: A CURATED AND INTEGRATED DATABASE OF GENES INVOLVED IN KIDNEY DISEASE

We have created a curated and integrated database, the Kidney Gene Database (KGDB) (http://www.urogene.org/kgdb) that contains current information about genes or genomic loci involved in human kidney disease. Genes that undergo molecular, genetic or epigenetic events that affect kidney function are identified through a biomedical literature search and catalogued in the database. Events that are currently screened for are gene amplification, mutation, deletion, polymorphism, loss of heterozygosity, DNA methylation and DNA hypomethylation. In addition, genes that are uniquely expressed in the kidney, as determined by analyzing the expressed sequence tags database and the Serial Analysis of Gene Expression database, are also included in KGDB. For each gene KGDB provides basic information about the gene product, a tissue type gene expression profile, links to protein, mRNA and genomic DNA sequence information, relevant literature citations and cross-references to other databases. We present KGDB, which is to our knowledge the first curated and integrated database of genes involved in human kidney disease. KGDB is free, widely accessible and easy to use, and it provides a wealth of relevant information. In addition, KGDB will be continuously updated every 6 months to include new information published in the biomedical literature or in gene expression databases. We envision that KGDB will serve as a valuable resource for scientists and clinicians.

Searching Online Mendelian Inheritance in Man (OMIM) for Information for Genetic Loci Involved in Human Disease

Online Mendelian Inheritance in Man (OMIM) is a non-sequence-based information resource that can be of tremendous use to genomics researchers, physicians, and patients. OMIM is the electronic version of the catalog of human genes and genetic disorders. It provides concise textual information from the literature on most human conditions having a genetic basis, as well as pictures illustrating the condition or disorder (where appropriate) and full citation information. This unit gives an overview of the OMIM database, the layout of the records, and the information that is available within each entry.

Implications of the Human Genome Project for obstetrics and gynecology.

The initial sequencing of the human genome should be regarded as a milestone in a road that stretches years into the future; the full ramifications of the Human Genome Project are still only being theorized. Researchers will benefit from the catalog of human genes in studies of the genetics of disease susceptibility and the cell biology of gene interactions. Clinicians will increasingly offer genetic or biochemical testing to identify those at highest risk for a number of diseases. Drug discovery will eventually follow newly possible studies of gene expression and protein function. However the Human Genome Project eventually shapes medicine, it is certain that physicians, particularly obstetricians and gynecologists, will need to be well versed in the scientific and ethical issues involved, inasmuch as we will likely be at the center of the most heated debates.

Target selection for Danio rerio functional genomics.

genesisVolume 30, Issue 3 p. 123-125 ArticleFree Access Target selection for Danio rerio functional genomics Eric W. Klee, Eric W. Klee University of Minnesota Medical School, Minneapolis, MinnesotaSearch for more papers by this authorStephen C. Ekker, Stephen C. Ekker University of Minnesota Medical School, Minneapolis, MinnesotaSearch for more papers by this authorLynda B.M. Ellis, Corresponding Author Lynda B.M. Ellis [email protected] University of Minnesota Medical School, Minneapolis, MinnesotaLaboratory Medicine and Pathology, University of Minnesota Medical School, Mayo Mail Code 609, 420 SE Delaware St., Minneapolis, MN 55455-0374Search for more papers by this author Eric W. Klee, Eric W. Klee University of Minnesota Medical School, Minneapolis, MinnesotaSearch for more papers by this authorStephen C. Ekker, Stephen C. Ekker University of Minnesota Medical School, Minneapolis, MinnesotaSearch for more papers by this authorLynda B.M. Ellis, Corresponding Author Lynda B.M. Ellis [email protected] University of Minnesota Medical School, Minneapolis, MinnesotaLaboratory Medicine and Pathology, University of Minnesota Medical School, Mayo Mail Code 609, 420 SE Delaware St., Minneapolis, MN 55455-0374Search for more papers by this author First published: 23 July 2001 https://doi.org/10.1002/gene.1045Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. LITERATURE CITED Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J Mol Biol 215: 403– 410. URL = http://www.ncbi.nlm.nih.gov/BLAST/ Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Rapp BA, Wheeler DL. 2000. GenBank. Nucleic Acids Res 28: 15– 18. URL = http://www.ncbi.nlm.nih.gov/Genbank/ Deihn M, Eisen MG, Botstein D, Brown PO. 2000. Large-scale identification of secreted and membrane-associated gene products using DNA microarrays. Nat Genet 25: 58– 62. Emanuelsson O, Nielsen H, Brunak S, von Heijne G. 2000. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol 300: 1005– 1016. URL = http://www.cbs.dtu.dk/services/TargetP/ Frishman D, Albermann K, Hani J, Heumann K, Metanomski A, Zollner A, Mewes H-W. 2001. Functional and structural genomics using PEDANT. Bioinformatics 17: 44– 57. URL = http://pedant.gsf.de/ Lee JJ, von Kessler DP, Parks S, Beachy PA. 1992. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell 71: 33– 50. Mignatti P, Rifkin DB. 1991. Release of basic fibroblast growth factor, an angiogenic factor devoid of secretory signal sequence: A trivial phenomenon or a novel secretion mechanism? J Cell Biochem 47: 201– 207. Nielsen H, Engelbrecht J, Brunak S, von Heijne G. 1997. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng 10: 1– 6. URL = http://www.cbs.dtu.dk/services/SignalP/ Quackenbush J, Cho J, Lee D, Liang F, Holt I, Karamycheva S, Parvizi B, Pertea G, Sultana R, White J. 2001. The TIGR Gene Indices: Analysis of gene transcript sequences in highly sampled eukaryotic species. Nucleic Acids Res 29: 159– 164. URL = http://www.tigr.org/tdb/tgi.shtml Sanger Centre. 2000. Sanger Centre to sequence zebrafish genome in new Wellcome Trust Initiative. Press Release 21November 2000. URL = http://www.sanger.ac.uk/Info/Press/001121.shtml Schuler GD. 1997. Pieces of the puzzle: Expressed sequence tags and the catalog of human genes. J Mol Med 75: 694– 698. URL = http://www.ncbi.nlm.nih.gov/UniGene/ Wheeler DL, Chappey C, Lash AE, Leipe DD, Madden TL, Schuler GD, Tatusova TA, Rapp BA. 2000. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 28: 10– 14. URL = http://www.ncbi.nlm.nih.gov/Taxonomy/ Citing Literature Volume30, Issue3July 2001Pages 123-125 ReferencesRelatedInformation

Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs

With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%–5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies.[The sequence data described in this paper have been submitted to the EMBL database under the accession nos. given in Table 2.]

Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%--5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies.

Pieces of the puzzle: expressed sequence tags and the catalog of human genes.

Pieces of the puzzle: expressed sequence tags and the catalog of human genes.

Reviews and Notes: Genetics: Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders

Reviews and Notes: Genetics: Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders

The 1979 catalog of human genes and chromosome assignments

The 1979 catalog of human genes and chromosome assignments

The catalog of human genes and chromosome assignments. A report on human genetic nomenclature and genes that have been mapped in man.

The catalog of human genes and chromosome assignments. A report on human genetic nomenclature and genes that have been mapped in man.