التفاصيل البيبلوغرافية
| العنوان: |
Quantifying microsatellite mutation rates from intestinal stem cell dynamics in Msh2-deficient murine epithelium |
| المؤلفون: |
Douglas J. Winton, Paul Potter, Filipe C. Lourenco, Edward Morrissey, Ann-Sofie Thorsen, Lee Hazelwood, Joseph Christopher, Richard Kemp, Sam Abujudeh |
| المساهمون: |
Winton, Douglas [0000-0001-6067-7927], Apollo - University of Cambridge Repository |
| المصدر: |
Genetics |
| بيانات النشر: |
Apollo - University of Cambridge Repository, 2019. |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Male, Mutation rate, microsatellite, Somatic cell, Mutant, Mitosis, Biology, Investigations, Genome Integrity and Transmission, 03 medical and health sciences, Mice, 0302 clinical medicine, Mutation Rate, Genetics, medicine, Animals, Intestinal Mucosa, intestine, mouse, 030304 developmental biology, 0303 health sciences, Intestinal epithelium, Molecular biology, Epithelium, Msh2, Mice, Inbred C57BL, Fixation (population genetics), Adult Stem Cells, medicine.anatomical_structure, MutS Homolog 2 Protein, 030220 oncology & carcinogenesis, Microsatellite, Female, Stem cell, mutation, Microsatellite Repeats |
| الوصف: |
Microsatellite sequences have an enhanced susceptibility to mutation, and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here, we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed, and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus, and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (∼50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2-deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 × 10−2) compared to wild-type epithelium (6.2 × 10−5). |
| وصف الملف: |
application/pdf |
| DOI: |
10.17863/cam.40204 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::90b177a67bbcab3971472a1e3595fa3b |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....90b177a67bbcab3971472a1e3595fa3b |
| قاعدة البيانات: |
OpenAIRE |