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Title: Functional and positional candidate gene studies of late-onset Alzheimer's disease
Author: Harold, Denise
ISNI:       0000 0004 2750 2289
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2004
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Alzheimer's disease is a neurodegenerative disorder characterised by progressive memory impairment, a decline in language function and a variety of behavioural symptoms. The majority of AD cases have an age at onset above 65 years and exhibit no clear pattern of inheritance. The only known genetic risk factor this late onset AD, LOAD, is the [Special character omitted]4 allele of the apolipoprotein E gene on chromosome 19. There is significant evidence of linkage to LOAD on chromosome 10q21-23. Therefore, nine candidate genes that map to this region were examined as susceptibility loci for the disease. In addition, a purely functional candidate, ADAM12, was examined on the basis of its homology to α-secretase enzymes, 58,752 basepairs of genomic sequence were screened by DHPLC, covering all exons, intron-exon boundaries and putative promoter regions, and 89 polymorphisms were detected. An additional 25 SNPs were identified from a SNP database. A two-stage strategy was employed. Variants were initially tested for association with AD by genotyping them in a small case-control sample, either in DNA pools or individually. Polymorphism showing a significant  difference between cases and controls were carried forward to the second stage and individually genotyped in a larger sample. A number of SNPs initially gave a positive result but after individual genotyping in a larger sample only 2 SNPs in the ADAM12 gene showed evidence for association with LOAD. As a large number of polymorphisms were examined, this may be a false positive finding, but this gene certainly warrants further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics ; RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry