期刊
ELIFE
卷 4, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.11389
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资金
- European Research Council [337415]
- Lister Institute of Preventive Medicine
- Rosetrees Trust
- Medical Research Council
- MRC [MC_U105192711] Funding Source: UKRI
- Medical Research Council [MC_U105192711] Funding Source: researchfish
- Rosetrees Trust [M442] Funding Source: researchfish
- European Research Council (ERC) [337415] Funding Source: European Research Council (ERC)
Aneuploidy in human eggs is the leading cause of pregnancy loss and Downs syndrome. Aneuploid eggs result from chromosome segregation errors when an egg develops from a progenitor cell, called an oocyte. The mechanisms that lead to an increase in aneuploidy with advanced maternal age are largely unclear. Here, we show that many sister kinetochores in human oocytes are separated and do not behave as a single functional unit during the first meiotic division. Having separated sister kinetochores allowed bivalents to rotate by 90 degrees on the spindle and increased the risk of merotelic kinetochore-microtubule attachments. Advanced maternal age led to an increase in sister kinetochore separation, rotated bivalents and merotelic attachments. Chromosome arm cohesion was weakened, and the fraction of bivalents that precociously dissociated into univalents was increased. Together, our data reveal multiple age-related changes in chromosome architecture that could explain why oocyte aneuploidy increases with advanced maternal age.
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