Somatic Mosaicism of Chromosome 21 in Alzheimer’s Disease

ResearchSpace/Manakin Repository

Show simple item record

dc.contributor.advisor Snell, R en
dc.contributor.author Hawkins, Victoria en
dc.date.accessioned 2017-07-25T21:42:04Z en
dc.date.issued 2017 en
dc.identifier.uri http://hdl.handle.net/2292/34494 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder primarily characterised by memory loss due to neural atrophy. AD pathology is typified by Tau tangles and senile plaques. The plaques are aggregations of beta-sheets of the amyloid beta peptide (Aβ). The Aβ peptide is produced from the amyloid precursor protein which is transcribed from the APP gene on chromosome 21. The hypothesis tested in this project was that increased dosage of the APP gene due to somatic mosaicism of trisomy 21 may contribute to AD. This dosage effect has been previously observed in Down’s syndrome (DS), a condition caused by three copies of chromosome 21, and which has a much higher incidence of AD. The relative frequency of chromosome 21 and 13 aneuploidy was measured in nuclei derived from three brain regions (middle frontal gyrus, cerebellum and the inferior parietal lobule) from clinically defined AD individuals and age matched controls. Aneuploidy was found to be widespread throughout the brain with no consistent differences in the frequency aneuploidy between the tested regions in controls or AD cases. AD cases on average had a higher level of total somatic aneuploidy than control individuals. The majority of this difference was due to the twofold increase in frequency of trisomy 21 in AD cases relative to controls. The underlying hypothesis is therefore supported by this observation. Correlation analysis of total aneuploidy frequency and the subtypes suggest a mechanistic origin of monosomy is likely to be different for trisomy. Importantly the frequency of total aneuploidy is correlated with age in controls but only with the trisomy 21 subtype in AD cases. This implies that the mechanism controlling aneuploidy in controls is lost in AD. Finally, a method was developed that allowed the detection of allele specific nondisjunction using genotyping heterozygous SNPs across chromosome 21. This method showed the ability to detect mosaicism down to a 1% level. Using this technique, this project provided evidence for the lack of allele specificity of the nondisjunction events responsible for aneuploidy cells detected in the brain, suggesting a potential mechanism by which aneuploidy accumulates randomly throughout the brain over a lifetime. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265050409602091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Somatic Mosaicism of Chromosome 21 in Alzheimer’s Disease en
dc.type Thesis en
thesis.degree.discipline Biomedical Science en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 639907 en
pubs.record-created-at-source-date 2017-07-26 en


Full text options

This item appears in the following Collection(s)

Show simple item record

Share

Search ResearchSpace


Advanced Search

Browse