PMC:540049 / 3758-10002 JSONTXT

{"project":"2_test","denotations":[{"id":"15608258-14681459-76758808","span":{"begin":204,"end":205},"obj":"14681459"},{"id":"15608258-15078858-76758809","span":{"begin":206,"end":207},"obj":"15078858"},{"id":"15608258-12519945-76758810","span":{"begin":219,"end":220},"obj":"12519945"},{"id":"15608258-14681461-76758811","span":{"begin":2043,"end":2044},"obj":"14681461"},{"id":"15608258-11752273-76758812","span":{"begin":2164,"end":2166},"obj":"11752273"},{"id":"15608258-15118671-76758813","span":{"begin":2341,"end":2343},"obj":"15118671"},{"id":"15608258-11687580-76758814","span":{"begin":4027,"end":4029},"obj":"11687580"},{"id":"15608258-11334433-76758814","span":{"begin":4027,"end":4029},"obj":"11334433"},{"id":"15608258-14679040-76758814","span":{"begin":4027,"end":4029},"obj":"14679040"},{"id":"15608258-14600816-76758814","span":{"begin":4027,"end":4029},"obj":"14600816"},{"id":"15608258-14578289-76758814","span":{"begin":4027,"end":4029},"obj":"14578289"},{"id":"15608258-15075390-76758815","span":{"begin":5190,"end":5192},"obj":"15075390"},{"id":"15608258-14681412-76758816","span":{"begin":5284,"end":5286},"obj":"14681412"}],"text":"DATA CONTENT\n\nAnnotated genomes\nT1DBase provides annotated genome sequence for human, rat and mouse. Currently 32 data tracks are available. The major sources for this information are the public Ensembl (6,7) and UCSC (8) genome databases, augmented by gene annotations produced internally by scientists at DIL and ISB. The DIL, upon dbSNP submission, also publishes its SNPs and primers through T1DBase.\nFrom the large number of data tracks available on Ensembl and UCSC, we have chosen those that are most relevant to T1D investigators. We are in the process of adding tracks and integrating tools not available on Ensembl and UCSC that are of specific interest to our users. Examples appear later.\nWe are committed to incorporating annotations from scientists in the community. Such annotations are manually reviewed before being added to the database.\n\nT1D prioritized regions\nThe system has information on prioritized regions in human, rat and mouse.\nFor human, there are three different kinds of prioritized regions: genetic linkage regions, regions defined through orthology with susceptibility regions in NOD congenic strains and candidate gene regions. There are 20 putative linkage regions, nine orthology regions and numerous candidate gene regions. For linkage and orthology regions, we provide a list of genes in the region. For linkage regions, we also provide a bibliography of publications studying the region, and a summary of LOD scores from the various studies. The candidate genes include ones reported in the literature as having a positive association with T1D, ones reported to be associated with other immune-mediated disorders such as asthma or rheumatoid arthritis that are also candidates for T1D and other genes of interest. The latter includes orthologs of mouse or rat genes associated with T1D, and genes involved in relevant pathways. For genes with literature support, we provide links to the publications.\nFor mouse, the database contains 27 susceptibility regions defined by the Mouse Genome Database (MGD) (9) with supporting literature. For rat, we have 18 regions and supporting literature from the Rat Genome Database (RGD) (10).\n\nGenetic association studies\nWe have assembled a dataset of genetic association studies pertaining to T1D in collaboration with the NIH Genetic Association Database (GAD) (11). The dataset covers about 100 genes and 180 publications, including published negative results. Under the collaboration, we carry out literature searches to identify relevant studies and pass the results to GAD for a final quality check and data entry.\n\nNOD strain database\nCongenic strains have been created to help identify regions of the NOD genome involved in T1D by introgressing chromosomal regions from resistant strains into the NOD mouse. To visualize the introgressed regions, we have developed a strain database. The strain database has the same data model as the feature database and allows the storage of strain information, such as strain name and its aliases, chromosomes, fine mapping markers and the name of the regions. These data are updated automatically with each update of the NCBI mouse genome build. When an interval is refined, scientists submit the new boundary markers via a webpage and the intervals are recalculated. The intervals are drawn through the Perl GD package. The database and the drawing tools may be of interest to other researchers working with congenic strains. Figure 2 illustrates the way strain information is displayed.\n\nBeta Cell Gene Expression Bank\nThe Beta Cell Gene Expression Bank is a dataset curated by Decio L. Eizirik and colleagues at the Laboratory for Experimental Medicine at the Free University of Brussels (ULB). There are two main components. One, called the Fast Track, reports the expression level of genes in beta cells under basal conditions and under conditions thought to induce beta cell dysfunction and death in T1D; these data come from a series of microarray experiments conducted in the Eizirik laboratory (12–16). The second component, called the Annotated Track, consists of manual annotation of gene function carried out by beta cell experts; priority is given to genes whose expression is changed when dysfunction is induced. The annotation includes information on the gene's function, its localization, disease association (with special focus on T1D and other autoimmune diseases), other interacting proteins and the phenotype after gene disruption in knockout/transgenic models. Key original references and reviews are provided.\nThe Fast Track currently has data for about 4500 genes from 30 Affymetrix microarray experiments. The Annotated Track contains more than 300 genes at present and is growing at a rate of 40–60 new genes per month.\n\nGene x tissue expression\nThis dataset indicates whether a gene is expressed in a limited set of T1D-relevant tissue types, namely, blood marrow, lymph nodes, pancreas, spleen and thymus based on an analysis of UniGene ESTs. This dataset is being replaced by a more comprehensive resource that combines microarray data from the Beta Cell Gene Expression Bank to characterize expression in beta cells and the GNF SymAtlas (17) to characterize expression elsewhere.\n\nPathways\nGenes are linked to pathways in the KEGG (18) and BioCarta (http://www.biocarta.com) databases. The BioCarta pathways are searched using the Cancer Genome Anatomy Project's (CGAP) Pathway Searcher (http://cgap.nci.nih.gov/Pathways/Pathway_Searcher). For KEGG pathways, it is possible to display a table of the genes involved which indicates whether the gene is located within a T1D candidate region.\n\nLinks between datasets\nWhen a user accesses a gene from any dataset on the website, a gene page is displayed that provides links to all T1DBase datasets that contain the gene. From this page, the user can also get to GBrowse and most other tools that can manipulate the gene. In addition, the gene page includes links to the following external resources: LocusLink, UniGene, HomoloGene, OMIM, GeneCards and EPConDB. We are in the process of developing similar links within the major tools on the site, so that tools can use information from any dataset to modify how data are visualized or processed.\n"}