Patel, Jessica (2017) Organisation of kinetochores in human oocytes. PhD thesis, University of Warwick.

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Abstract

A large proportion of human pregnancies have the wrong number of chromosomes, known as aneuploidy, with the chances of having an affected pregnancy increasing with maternal age. The majority of these errors can be traced back to the egg (oocyte), which undergoes two meiotic cell divisions to generate a cell with half the number of chromosomes of a somatic cell. The first meiotic division is particularly error-prone and accounts for a significant proportion of aneuploidies in early embryos. This first division is a unique form of cell division because it entails separation of homologous chromosome pairs and co-segregation of identical sister chromatids at anaphase (in mitosis and meiosis II, by contrast, sister chromatids separate at anaphase). The kinetochore is a multiprotein structure that assembles on the centromeres of chromosomes and facilitates chromosome segregation by forming attachments to spindle fibres emanating from one of the spindle poles. For a successful meiosis I division, kinetochores on sister chromatids must act as a single functional unit. In mouse and yeast this is achieved through close physical association of meiotic sister kinetochores; in humans, however, little is known about the arrangement of sisters in oocytes, largely due to the limited availability of human oocytes for research. In this project, I show that in human meiosis I stage oocytes donated to research by women undergoing assisted reproduction, sister kinetochores are not physically fused and are each capable of forming individual attachments to spindle microtubule fibres. I also found a significant increase in the distance between sister kinetochores in patients over 35 years of age, which may indicate a decline in inter-kinetochore cohesion over time. These unique features of sister kinetochore geometry in human oocytes may shed light on why meiosis in humans is susceptible to error with increasing maternal age.

Item Type:	Thesis (PhD)
Subjects:	R Medicine > RB Pathology
Library of Congress Subject Headings (LCSH):	Aneuploidy, Human chromosome abnormalities, Oogenesis, Human chromosomes
Official Date:	May 2017
Dates:	Date Event May 2017 Submitted
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Hartshorne, Geraldine ; McAinsh, Andrew D.
Sponsors:	Montreal Reproductive and Regenerative Medicine Foundation
Extent:	x, 138 leaves : illustrations
Language:	eng

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