Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27424524
DOI
10.1016/j.canlet.2016.07.011
PII: S0304-3835(16)30406-2
Knihovny.cz E-resources
- Keywords
- Chromosomal integrity, Cytogenetics, DNA double-stranded break, Spindle checkpoint,
- MeSH
- Genes, cdc * MeSH
- Chromosome Aberrations * MeSH
- DNA Breaks, Double-Stranded MeSH
- Genetic Variation * MeSH
- Intracellular Signaling Peptides and Proteins genetics MeSH
- Nuclear Proteins genetics MeSH
- M Phase Cell Cycle Checkpoints genetics MeSH
- Humans MeSH
- Lymphocytes chemistry pathology MeSH
- Mad2 Proteins genetics MeSH
- Models, Genetic MeSH
- Cell Cycle Proteins genetics MeSH
- Securin genetics MeSH
- Healthy Volunteers MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Intracellular Signaling Peptides and Proteins MeSH
- Nuclear Proteins MeSH
- Mad2 Proteins MeSH
- MAD2L1 protein, human MeSH Browser
- pituitary tumor-transforming protein 1, human MeSH Browser
- Cell Cycle Proteins MeSH
- Securin MeSH
- Zwilch protein, human MeSH Browser
- ZWINT protein, human MeSH Browser
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.
References provided by Crossref.org
Genetic and environmental associations of nonspecific chromosomal aberrations
