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Title: The origin of aneuploidy in humans : data from oocytes and preimplantation embryos
Author: Ghevaria, H.
ISNI:       0000 0004 7659 9304
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Human reproduction is an error prone process. Preimplantation embryos generated through IVF are known to be aneuploid to a large extent. This thesis investigated various questions relating to the origins of human aneuploidy by analysing human gametic material and embryos from routine IVF patients and carriers of translocations undergoing PGD. The first aim was to determine the relative incidence of pre-meiotic errors indicative of germinal mosaicism compared to those occurring at meiosis I. Human oocytes, unexposed to sperm (n=126) at different maturation stages were analysed by array-CGH. Pre-meiotic errors occurred in 9.8% of informative oocytes (n=102). Overall, 38% of aneuploidy was caused by germinal mosaicism compared with 62% that was due to a meiosis I error. The second aim was to determine the origin and significance of aneuploidy events unrelated to the translocation imbalances which occur in about 50% of embryos from carriers of reciprocal and Robertsonian translocations undergoing PGD by array-CGH. 83 untransferred embryos having at least one of these events were followed up by FISH (n=63) or array-CGH (n=20). Meiotic and mitotic events were almost equal (60 versus 64), 97 affected whole chromosomes (58 meiotic, 39 mitotic) and 27 were segmental (two meiotic, 25 mitotic). Parental origin of 22 meiotic events investigated was maternal. Additional aneuploidies merit full consideration in the choice of which embryos to transfer. The outcome of the third aim showed that the shape characteristics of the quadrivalent formed at pachytene could predict the type of meiotic segregation in embryos in 26 out of 28 (93%) carriers of reciprocal translocations. Meiotic segregation patterns were determined post FISH/aCGH follow up of embryos. Translocations carried by female partner or those involving acrocentric chromosomes showed a high incidence of 3:1 segregation pattern. Meiotic outcome in embryos from two carriers of uncommon Y-autosome translocations were analysed and discussed.
Supervisor: Delhanty, J. ; Sengupta, S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available