An investigation of genome stability in human female meiosis by genome-wide chromosome fingerprinting and copy number analysis

In both natural and assisted human conceptions, the incidence of extra or missing chromosomes (aneuploidy) increases dramatically in women of advanced maternal age (35 years and above). An estimated 5-30% of all natural conceptions are thought to be aneuploid, of which 70-90% of supernumerary chromosomes are expected to be maternally inherited. In addition, structural abnormalities lead to segmental aneuploidies, which are poorly understood. In both cases, the resulting genomic imbalance is a major cause of infertility, pregnancy loss, and congenital disorders in human. Within the last five years, technological advances have improved the resolution for genome content analysis in trophectoderm biopsies (3-10 cells) taken from preimplantation embryos. Using these technologies and improving them to single cell resolution will allow unprecedented studies of the rates and origins of aneuploidies in the human germline. In this thesis, I have assessed and discussed the clinical incidence and impact of mosaic and segmental chromosome abnormalities in preimplantation embryos (Chapter 3); the requirement for single cell genomics, and develop of a pipeline for concurrent NGS and SNP microarray analysis on individual products of meiosis (Chapter 4); and development of a highprecision, single cell genotyping algorithm through collaboration, to ask questions about genome diversification and human genome evolution (Chapter 5). Collectively, my findings show that the chromosomes are highly unstable in the human eggs and preimplantation embryos and discuss the implication for embryo testing

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Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans. [Abstract copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

grid infrastructure for molecular simulations: The eMinerals minigrid as a prototype integrated compute and data grid. Molecular Simulations 31

RG6 6AY This paper describes a prototype grid infrastructure, called the “eMinerals minigrid”, for molecular simulation scientists. which is based on an integration of shared compute and data resources. We describe the key components, namely the use of Condor pools, Linux/Unix clusters with PBS and IBM’s LoadLeveller job handling tools, the use of Globus for security handling, the use of Condor-G tools for wrapping globus job submit commands, Condor’s DAGman tool for handling workflow, the Storage Resource Broker for handling data, and the CCLRC dataportal and associated tools for both archiving data with metadata and making data available to other workers