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

Blanshard, Robert Christopher (2019) An investigation of genome stability in human female meiosis by genome-wide chromosome fingerprinting and copy number analysis. Doctoral thesis (PhD), University of Sussex.

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Abstract

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.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Depositing User: Library Cataloguing
Date Deposited: 15 Jul 2019 13:26
Last Modified: 01 Sep 2021 08:08
URI: http://sro.sussex.ac.uk/id/eprint/84919

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