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Revision 59 (Jason Bobe, 03/04/2010 02:39 PM) → Revision 60/88 (Jason Bobe, 03/04/2010 03:14 PM)
= Genotype + Environment = Trait Evidence (GET-E) Database = The '''GET-E''' project was started by Abraham Rosenbaum, Joe Thakuria, Xiaodi Wu and Alexander Wait Zaranek to help the [http://personalgenomes.org Personal Genome Project], the clinical genetics community, and, the general public interpret individual genomes. The database is closely integrated with [wiki:Trait-o-matic]. You can find the PGP production server at: * http://evidence.personalgenomes.org A development sandbox can be found at: * http://evidence-dev.personalgenomes.org Many contributors helped make '''GET-E''' possible. You can find specific contributions at: * http://evidence.personalgenomes.org/editors Please help the project by editing the database, writing software tools that use the database (eg. Trait-o-matic/AETAS) or by making suggestions on the wiki! == Field Descriptions and Editing Guidelines == === Short Summary === * free text providing a one line summary of clinical action to be undertaken given this variant (possibly modified by known phenotypes). === Variant Quality Data === Each of these fields is a sliding scale of 0-5 where 0 represents no evidence and 5 strong evidence that the Impact is correct. Where the data is not entered the default is N/A. When Genetests and/or the literature correlate this variant with a number of phenotypes the impact should be reported for the most extreme condition a. Computational: One star for each consistent prediction and one star subtracted for conflicting results from: i. evolutionary conservation (minimum of three species) i. presence in active domain i. SIFT i. !PolyPhen i. NBLOSUM >= 2 i. GVGD i. Other variants in this gene cause similar disease i. etc... a. Functional: One star for each experiment supporting the result, and penalize one star for conflicting results from: i. enzyme extracts i. cell lines i. animal models i. etc... a. Case/Control: A combination of odds ratio and significance test (currently using Fisher's Exact Test). For protective alleles, use inverse OR = 1 / OR. Do not count related individuals, count probands -- ie. one per family i. 0 stars if no higher ranking is allowed i. 1 star if OR>1 and significance <= 0.1 i. 2 stars if OR>=1.5 and significance <= 0.05 i. 3 stars if OR>=2 and significance <= 0.025 i. 4 stars if OR>=3 and significance <= 0.01 i. 5 stars if OR>=5 and significance <= 0.0001 a. Familial Disease Segregation i. 0 stars for no segregation (LOD < -2) i. 1 star if segregation exists in one family pedigree i. 2 stars for segregation in more than one family with some conflicting information (e.g. asymptomatic carrier of young age or possibility of second causative mutation) i. 3 stars for more than one family no conflicting information i. 4 stars for LOD > 2 i. 5 stars for LOD > 3 a. Disease severity: downgraded according to disease penetrance (eg. Crohn's disease would be moderate or severe, but "increased susceptibility" is only increased the chances by ~.15% and so is called mild) i. 0 stars for benign i. 1 star for very low expectation of having symptoms for this genotype, very low penetrance mild effect (eg. Susceptibility increased susceptibility to crohn's with OR = 4.5, causing a ~.2% risk of Crohn's) Crohn's disease) i. 2 stars for mild effect on quality of life or unlikely to be symptomatic (Cystinuria) (eg. Alpha-1-antitrypsin deficiency) i. 3 stars for moderate effect on quality of life (eg. Familial mediterranean fever) Cystineria) i. 4 stars for severe effect: causes serious disability or reduces life expectancy potentially lethal (eg. Sickle-cell, Stargardt's disease) sickle-cell) i. 5 stars for very severe effect: early lethal or severe damage (eg. Familial adenomatous polypopsis, adrenoleukodystrophy) Bardet-Biedl, PKU) a. Treatability: i. 0 stars for no clinical evidence supporting intervention (eg. PAF acetylhydrolase deficiency) i. 1 star for uncurable: treatment only to alleviate symptoms (eg. adrenoleukodystrophy) i. 2 stars for potentially treatable: Treatment is in development or controversial i. 3 stars for treatable but a significant fraction do not require treatment (Cystinuria) i. 4 stars for treatable: Standard treatment reduces the amount of mortality/morbidity but does not eliminate it (eg. Sickle-cell disease) i. 5 stars for extremely treatable: Well-established treatment essentially eliminates the effect of the disease (eg. PKU) === Impact === a. Pathogenic: Causative for disease. a. Benign: No clinically significant phenotype. a. Protective: Protective from disease. a. Pharmacogenetic: Clinically significant phenotype in the presence of a pharmacological agent. a. NR: Not reviewed. In addition to these impacts, qualifiers will be added according to the variant quality information (ie. the stars). For pathogenic, pharmacogenetic, and protective variants: a. (no qualifier given): at least 4 stars in one of the human evidence categories (case/control or familial), at least 4 stars in one of the clinical categories (severity or treatability), and at least 14 stars total. a. "likely": at least 3 stars in one of the human evidence categories, at least 3 stars in one of the clinical categories, and at least 10 stars total. a. "uncertain": all the rest. For benign: a. (no qualifier given): at least 4 stars in one of the human evidence categories, and at least 10 stars total. a. "likely": at least 3 stars in one of the human evidence categories, and at least 6 stars total. a. "uncertain": all the rest. When Genetests and/or the literature give multiple phenotypes for a variant, the impact should be reported for the most extreme condition and annotated as such in the ''short summary''. In the future we hope to list different phenotypes separately. === Inheritance Pattern === a. Dominant a. Recessive a. Other: A defined form of inheritance that is neither dominant or recessive (e.g. modifier, co-dominant, incomplete penetrance). These variants will get prioritized due to their potential phenotypic affect should the additional factors be present. a. Undefined: Undefined in the literature. a. Unknown: The default value for all variants and all variants without literature. === Summary of published research, and additional commentary === * Free text providing a comprehensive review of the variant including youngest age of onset, oldest age of onset and oldest asymptomatic individual. === Allele Frequency === * Automatically generated frequencies for the !HapMap Project, 1000 Genomes Project and the weighted average of the two. Sub-population frequencies and homozygous/heterozygous break-downs are currently not shown. === Publications === * User-entered publications and user entered synopses of the relevant details from the publication. A short summary is also entered for each paper (as above). === Genomes === * Automatically generated list of all genomes from Trait-o-matic in which this variant is seen. Additionally, specific actions taken by each individual harboring the variant can be reported. === Other External References === These are automatically generated by web "robots": a. dbSNP: The link to the dbSNP entry for this nucleotide position (for this nucleotide change?) a. Genetests: Link to all clinical laboratories performing diagnostic tests on this gene and the list of diseases that the labs are looking for. a. Web Search Results: A web search for this exact variant using the Yahoo search engine === Edit History === * Automatically generated history of all page edits with the contributor's name. == To Do == * [wiki:GET-Evidence/23andWe] == Suggestions == * your suggestion here.