气候变化领域集成服务门户(CCPortal): Mathematical modeling of human oocyte aneuploidy

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DOI	10.1073/pnas.1912853117
	Mathematical modeling of human oocyte aneuploidy
	Tyc K.M.; McCoy R.C.; Schindler K.; Xing J.
发表日期	2020
ISSN	0027-8424
起始页码	10455
结束页码	10464
卷号	117 期号:19
英文摘要	Aneuploidy is the leading contributor to pregnancy loss, congenital anomalies, and in vitro fertilization (IVF) failure in humans. Although most aneuploid conceptions are thought to originate from meiotic division errors in the female germline, quantitative studies that link the observed phenotypes to underlying error mechanisms are lacking. In this study, we developed a mathematical modeling framework to quantify the contribution of different mechanisms of erroneous chromosome segregation to the production of aneuploid eggs. Our model considers the probabilities of all possible chromosome gain/loss outcomes that arise from meiotic errors, such as nondisjunction (NDJ) in meiosis I and meiosis II, and premature separation of sister chromatids (PSSC) and reverse segregation (RS) in meiosis I. To understand the contributions of different meiotic errors, we fit our model to aneuploidy data from 11,157 blastocyst-stage embryos. Our bestfitting model captures several known features of female meiosis, for instance, the maternal age effect on PSSC. More importantly, our model reveals previously undescribed patterns, including an increased frequency of meiosis II errors among eggs affected by errors in meiosis I. This observation suggests that the occurrence of NDJ in meiosis II is associated with the ploidy status of an egg. We further demonstrate that the model can be used to identify IVF patients who produce an extreme number of aneuploid embryos. The dynamic nature of our mathematical model makes it a powerful tool both for understanding the relative contributions of mechanisms of chromosome missegregation in human female meiosis and for predicting the outcomes of assisted reproduction. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Aneuploidy; Chromosome missegregation; Maternal age effect; Mathematical modeling; Meiosis
语种	英语
scopus关键词	adult; aneuploidy; Article; blastocyst; chromosome segregation; cohort analysis; embryo; female; human; human cell; in vitro fertilization; karyotype; maternal age; mathematical model; meiosis; middle aged; mitosis; nondisjunction; oocyte; patient identification; priority journal; reproduction; sister chromatid; chromosome deletion; genetics; metabolism; oocyte; physiology; preimplantation genetic diagnosis; theoretical model; Aneuploidy; Blastocyst; Chromosome Deletion; Chromosome Segregation; Female; Fertilization in Vitro; Humans; Karyotype; Maternal Age; Meiosis; Models, Theoretical; Nondisjunction, Genetic; Oocytes; Preimplantation Diagnosis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160291
作者单位	Tyc, K.M., Department of Genetics, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States, Human Genetic Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States, Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, United States; McCoy, R.C., Department of Biology, Johns Hopkins University, Baltimore, MD 21218, United States; Schindler, K., Department of Genetics, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States, Human Genetic Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States; Xing, J., Department of Genetics, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States, Human Genetic Institute of New Jersey, Rutgers the State University of New Jersey, Piscataway, NJ 08854, United States
推荐引用方式 GB/T 7714	Tyc K.M.,McCoy R.C.,Schindler K.,et al. Mathematical modeling of human oocyte aneuploidy[J],2020,117(19).
APA	Tyc K.M.,McCoy R.C.,Schindler K.,&Xing J..(2020).Mathematical modeling of human oocyte aneuploidy.Proceedings of the National Academy of Sciences of the United States of America,117(19).
MLA	Tyc K.M.,et al."Mathematical modeling of human oocyte aneuploidy".Proceedings of the National Academy of Sciences of the United States of America 117.19(2020).