Non-specific chromosomal aberrations (CAs) are microscopically detected in about 1% of lymphocytes drawn from healthy persons. Causes of CAs in general population are not known but they may be related to risk of cancer. In view of the importance of the mitotic checkpoint machinery on maintaining chromosomal integrity we selected 9 variants in main checkpoint related genes (BUB1B, BUB3, MAD2L1, CENPF, ESPL1/separase, NEK2, PTTG1/securin, ZWILCH and ZWINT) for a genotyping study on samples from healthy individuals (N = 330 to 729) whose lymphocytes had an increased number of CAs compared to persons with a low number of CAs. Genetic variation in individual genes played a minor importance, consistent with the high conservation and selection pressure of the checkpoint system. However, gene pairs were significantly associated with CAs: PTTG1-ZWILCH and PTTG1-ZWINT. MAD2L1 and PTTG1 were the most common partners in any of the two-way interactions. The results suggest that interactions at the level of cohesin (PTTG1) and kinetochore function (ZWINT, ZWILCH and MAD2L1) contribute to the frequency of CAs, suggesting that gene variants at different checkpoint functions appeared to be required for the formation of CAs.
- Klíčová slova
- Chromosomal integrity, Cytogenetics, DNA double-stranded break, Spindle checkpoint,
- MeSH
- CDC geny * MeSH
- chromozomální aberace * MeSH
- dvouřetězcové zlomy DNA MeSH
- genetická variace * MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- jaderné proteiny genetika MeSH
- kontrolní body M fáze buněčného cyklu genetika MeSH
- lidé MeSH
- lymfocyty chemie patologie MeSH
- Mad2 protein genetika MeSH
- modely genetické MeSH
- proteiny buněčného cyklu genetika MeSH
- sekurin genetika MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- intracelulární signální peptidy a proteiny MeSH
- jaderné proteiny MeSH
- Mad2 protein MeSH
- MAD2L1 protein, human MeSH Prohlížeč
- pituitary tumor-transforming protein 1, human MeSH Prohlížeč
- proteiny buněčného cyklu MeSH
- sekurin MeSH
- Zwilch protein, human MeSH Prohlížeč
- ZWINT protein, human MeSH Prohlížeč
