Human Genetics

, Volume 113, Issue 3, pp 258–267

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

Authors

  • Denise Harold
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Timothy Peirce
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Valentina Moskvina
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Amanda Myers
    • Laboratory of Neurogenetics, MSC 0900, Building 9, Room 1N108, National Institute of AgingNational Institute of Health
  • Susan Jones
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Paul Hollingworth
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Pamela Moore
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Simon Lovestone
    • Institute of Psychiatry
  • John Powell
    • Institute of Psychiatry
  • Catherine Foy
    • Institute of Psychiatry
  • Nicola Archer
    • Institute of Psychiatry
  • Sarah Walter
    • Institute of Psychiatry
  • Amanda Edmonson
    • Institute of Psychiatry
  • Stephen McIlroy
    • Department of Geriatric MedicineQueen's University Belfast
  • David Craig
    • Department of Geriatric MedicineQueen's University Belfast
  • Peter A. Passmore
    • Department of Geriatric MedicineQueen's University Belfast
  • Alison Goate
    • Departments of Psychiatry and NeurologyWashington University School of Medicine
  • John Hardy
    • Laboratory of Neurogenetics, MSC 0900, Building 9, Room 1N108, National Institute of AgingNational Institute of Health
  • Michael O'Donovan
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Julie Williams
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Malcolm Liddell
    • Department of Psychological MedicineUniversity of Wales College of Medicine
  • Michael J. Owen
    • Department of Psychological MedicineUniversity of Wales College of Medicine
    • Department of Psychological MedicineUniversity of Wales College of Medicine
    • Institute of Medical GeneticsUniversity of Wales College of Medicine
Original Investigation

DOI: 10.1007/s00439-003-0960-2

Cite this article as:
Harold, D., Peirce, T., Moskvina, V. et al. Hum Genet (2003) 113: 258. doi:10.1007/s00439-003-0960-2

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.

Copyright information

© Springer-Verlag 2003