Next generation sequencing of CLU, PICALM and CR1: Pitfalls and potential solutions

Research output: Contribution to journalArticle

  • External authors:
  • Jenny Lord
  • James Turton
  • Christopher Medway
  • Hui Shi
  • Kristelle Brown
  • James Lowe
  • David Mann
  • Noor Kalsheker
  • Peter Passmore
  • Kevin Morgan


Abstract: CLU, PICALM and CR1 were identified as genetic risk factors for late onset Alzheimer's disease (AD) in two large genome wide association studies (GWAS) published in 2009, but the variants that convey this alteration in disease risk, and how the genes relate to AD pathology is yet to be discovered. A next generation sequencing (NGS) project was conducted targeting CLU, CR1 and PICALM, in 96 AD samples (8 pools of 12), in an attempt to discover rare variants within these AD associated genes. Inclusion of repetitive regions in the design of the SureSelect capture lead to significant issues in alignment of the data, leading to poor specificity and a lower than expected depth of coverage. A strong positive correlation (0.964, p

Bibliographical metadata

Original languageEnglish
Pages (from-to)262-275
Number of pages13
JournalInternational Journal of Molecular Epidemiology and Genetics
Issue number4
Publication statusPublished - 2012