Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-05-21

AUTHORS

Denise Harold, Timothy Peirce, Valentina Moskvina, Amanda Myers, Susan Jones, Paul Hollingworth, Pamela Moore, Simon Lovestone, John Powell, Catherine Foy, Nicola Archer, Sarah Walter, Amanda Edmonson, Stephen McIlroy, David Craig, Peter A. Passmore, Alison Goate, John Hardy, Michael O'Donovan, Julie Williams, Malcolm Liddell, Michael J. Owen, Lesley Jones

ABSTRACT

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium. More... »

PAGES

258-267

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-003-0960-2

DOI

http://dx.doi.org/10.1007/s00439-003-0960-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017179029

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12759818


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