BRCA1 Circos: a visualisation resource for functional analysis of missense variants
| العنوان: | BRCA1 Circos: a visualisation resource for functional analysis of missense variants |
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| المؤلفون: | Jhuraney, A., Velkova, A., Johnson, R.C., Kessing, B., Carvalho, R.S., Whiley, P., Spurdle, A.B., Vreeswijk, M.P.G., Caputo, S.M., Millot, G.A., Vega, A., Coquelle, N., Galli, A., Eccles, D., Blok, M.J., Pal, T., Luijt, R.B. van der, Pena, M.S., Neuhausen, S.L., Donenberg, T., Machackova, E., Thomas, S., Vallee, M., Couch, F.J., Tavtigian, S.V., Glover, J.N.M., Carvalho, M.A., Brody, L.C., Sharan, S.K., Monteiro, A.N., ENIGMA Evidence-Based Network |
| المساهمون: | University of South Florida [Tampa] (USF), H. Lee Moffitt Cancer Center and Research Institute, National Human Genome Research Institute (NHGRI), Frederick National Laboratory for Cancer Research (FNLCR), Instituto Nacional de Câncer [Rio de Janeiro, Brésil], Instituto Federal de Educação, Ciência e Tecnologia de São Paulo (IFSP), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Institut Curie [Paris], Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), University of Alberta, Instituto di fisiologia clinica, University of Southampton, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center [Utrecht], CIBER de Enfermedades Raras (CIBERER), Beckman Research Institute of the City of Hope, University of Miami Leonard M. Miller School of Medicine (UMMSM), Masaryk Memorial Cancer Institute (RECAMO), Salisbury District Hospital, International Agency for Cancer Research (IACR), Mayo Clinic [Rochester], University of Utah School of Medicine [Salt Lake City], National Cancer Institute Frederick, This work was funded by H. Lee Moffitt Cancer Center Foundation (Milesfor Moffitt), and the US National Cancer Institute. The ENIGMA consortium is funded by a supplement to NIH RO1 award CA116167, The authors would like to sincerely thank Tyra Wolfsberg and Suiyuan Zhang for helping with webpage development and all individuals and families who have generously donated their time, samples and information to facilitate research on the predisposition factors of breast and ovarian cancer, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON) |
| المصدر: | Journal of Medical Genetics, 52(4), 224-230 Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2015, 52 (4), pp.224-230. ⟨10.1136/jmedgenet-2014-102766⟩ Journal of Medical Genetics, 52(4), 224-230. BMJ Publishing Group JOURNAL OF MEDICAL GENETICS, 52(4), 224-230. BMJ PUBLISHING GROUP Journal of Medical Genetics, 52, 224. BMJ Publishing Group |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Datasets as Topic, LIGASE ACTIVITY, MUTATION-POSITIVE FAMILIES, Databases, Genetic, SEQUENCE VARIANTS, Missense mutation, Genetics(clinical), MESH: Datasets as Topic, Molecular genetics, MESH: DNA Mutational Analysis, Non-U.S. Gov't, skin and connective tissue diseases, Genetics (clinical), MESH: Databases, Genetic, Ovarian Neoplasms, Genetics, education.field_of_study, medicine.diagnostic_test, MESH: Genetic Testing, BRCA1 Protein, Research Support, Non-U.S. Gov't, UNKNOWN CLINICAL-SIGNIFICANCE, MESH: Genetic Predisposition to Disease, BREAST-CANCER RISK, RING-DOMAIN, 3. Good health, MESH: Ovarian Neoplasms, MESH: Internet, UNCERTAIN SIGNIFICANCE, Medical genetics, Female, MESH: Computer Graphics, MESH: Computational Biology, medicine.medical_specialty, Population, Mutation, Missense, Breast Neoplasms, Biology, Research Support, OVARIAN-CANCER, N.I.H, MESH: Software, Germline mutation, Research Support, N.I.H., Extramural, GENETIC-ANALYSIS, Journal Article, Cancer Genetics, Computer Graphics, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Ligase activity, Clinical genetics, NEGATIVE WOMEN, education, Genetic testing, MESH: BRCA1 Protein, Internet, MESH: Mutation, Missense, MESH: Humans, Cancer: breast, Extramural, Computational Biology, BRCA1, Database Management Systems, MESH: Female, Software, MESH: Breast Neoplasms, MESH: Database Management Systems |
| الوصف: | BACKGROUND: Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leading to single amino acid changes. Their impact on protein function cannot be directly inferred from sequence information, precluding assessment of their pathogenicity. Thus, functional assays are critical to assess the impact of these VUS on protein activity. BRCA1 is a multifunctional protein and different assays have been used to assess the impact of variants on different biochemical activities and biological processes.METHODS AND RESULTS: To facilitate VUS analysis, we have developed a visualisation resource that compiles and displays functional data on all documented BRCA1 missense variants. BRCA1 Circos is a web-based visualisation tool based on the freely available Circos software package. The BRCA1 Circos web tool (http://research.nhgri.nih.gov/bic/circos/) aggregates data from all published BRCA1 missense variants for functional studies, harmonises their results and presents various functionalities to search and interpret individual-level functional information for each BRCA1 missense variant.CONCLUSIONS: This research visualisation tool will serve as a quick one-stop publically available reference for all the BRCA1 missense variants that have been functionally assessed. It will facilitate meta-analysis of functional data and improve assessment of pathogenicity of VUS. |
| وصف الملف: | text; application/pdf; image/pdf |
| اللغة: | English |
| تدمد: | 0022-2593 1468-6244 |
| DOI: | 10.1136/jmedgenet-2014-102766 |
| DOI: | 10.1136/jmedgenet-2014-102766⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::915b3b67cbed5726facc6900cb917651 https://doi.org/10.1136/jmedgenet-2014-102766 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....915b3b67cbed5726facc6900cb917651 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2014-102766 |