Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms–mismatch repair (MAPP-MMR) Communicated by Marc Greenblatt
dc.contributor.author | Chao, Elizabeth C. | en_US |
dc.contributor.author | Velasquez, Jonathan L. | en_US |
dc.contributor.author | Witherspoon, Mavee S. L. | en_US |
dc.contributor.author | Rozek, Laura S. | en_US |
dc.contributor.author | Peel, David J. | en_US |
dc.contributor.author | Ng, Pauline | en_US |
dc.contributor.author | Gruber, Stephen B. | en_US |
dc.contributor.author | Watson, Patrice | en_US |
dc.contributor.author | Rennert, Gad | en_US |
dc.contributor.author | Anton-Culver, Hoda | en_US |
dc.contributor.author | Lynch, Henry | en_US |
dc.contributor.author | Lipkin, Steven M. | en_US |
dc.date.accessioned | 2008-06-04T14:40:07Z | |
dc.date.available | 2009-06-01T20:08:52Z | en_US |
dc.date.issued | 2008-06 | en_US |
dc.identifier.citation | Chao, Elizabeth C.; Velasquez, Jonathan L.; Witherspoon, Mavee S.L.; Rozek, Laura S.; Peel, David; Ng, Pauline; Gruber, Stephen B.; Watson, Patrice; Rennert, Gad; Anton-Culver, Hoda; Lynch, Henry; Lipkin, Steven M. (2008). "Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms–mismatch repair (MAPP-MMR) Communicated by Marc Greenblatt ." Human Mutation 29(6): 852-860. <http://hdl.handle.net/2027.42/58649> | en_US |
dc.identifier.issn | 1059-7794 | en_US |
dc.identifier.issn | 1098-1004 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/58649 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18383312&dopt=citation | en_US |
dc.description.abstract | Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC), is the most common known genetic syndrome for colorectal cancer (CRC). MLH1/MSH2 mutations underlie approximately 90% of Lynch syndrome families. A total of 24% of these mutations are missense. Interpreting missense variation is extremely challenging. We have therefore developed multivariate analysis of protein polymorphisms–mismatch repair (MAPP-MMR), a bioinformatic algorithm that effectively classifies MLH1/MSH2 deleterious and neutral missense variants. We compiled a large database (n>300) of MLH1/MSH2 missense variants with associated clinical and molecular characteristics. We divided this database into nonoverlapping training and validation sets and tested MAPP-MMR. MAPP-MMR significantly outperformed other missense variant classification algorithms (sensitivity, 94%; specificity, 96%; positive predictive value [PPV] 98%; negative predictive value [NPV], 89%), such as SIFT and PolyPhen. MAPP-MMR is an effective bioinformatic tool for missense variant interpretation that accurately distinguishes MLH1 / MSH2 deleterious variants from neutral variants. Hum Mutat 29(6), 852–860, 2008. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 236999 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms–mismatch repair (MAPP-MMR) Communicated by Marc Greenblatt | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Epidemiology, and Human Genetics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Epidemiology, and Human Genetics, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California | en_US |
dc.contributor.affiliationother | J. Craig Venter Institute for Human Genetics, Rockville, Maryland | en_US |
dc.contributor.affiliationother | Hereditary Cancer Institute, Creighton University School of Medicine, Omaha, Nebraska | en_US |
dc.contributor.affiliationother | Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel ; CHS National Cancer Control Center, Haifa, Israel | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California | en_US |
dc.contributor.affiliationother | Hereditary Cancer Institute, Creighton University School of Medicine, Omaha, Nebraska | en_US |
dc.contributor.affiliationother | Genetic Epidemiology Research Institute, University of California, Irvine, Irvine, California ; Cancer Genetics Clinic, Division of Hematology-Oncology, University of California, Irvine, 204 Sprague Hall, ZC 4038, Irvine, CA 92697 | en_US |
dc.identifier.pmid | 18383312 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/58649/1/20735_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/humu.20735 | en_US |
dc.identifier.source | Human Mutation | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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