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

Jenny Lord; James Turton; Christopher Medway; Hui Shi; Kristelle Brown; James Lowe; David Mann; Stuart Pickering-Brown; Noor Kalsheker; Peter Passmore; Kevin Morgan

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

Jenny Lord, James Turton, Christopher Medway, Hui Shi, Kristelle Brown, James Lowe, David Mann, Stuart Pickering-Brown, Noor Kalsheker, Peter Passmore, Kevin Morgan

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	English
Pages (from-to)	262-275
Number of pages	13
Journal	International Journal of Molecular Epidemiology and Genetics
Volume	3
Issue number	4
Publication status	Published - 2012

Keywords

Alzheimer's disease
CLU
CR1
Genes
Next generation sequencing
PICALM

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http://www.ijmeg.org/files/IJMEG1210001.pdf

Cite this

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abstract = "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",

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T1 - Next generation sequencing of CLU, PICALM and CR1: Pitfalls and potential solutions

AU - Lord, Jenny

AU - Turton, James

AU - Medway, Christopher

AU - Shi, Hui

AU - Brown, Kristelle

AU - Lowe, James

AU - Mann, David

AU - Pickering-Brown, Stuart

AU - Kalsheker, Noor

AU - Passmore, Peter

AU - Morgan, Kevin

N1 - G0701441, Medical Research Council, United Kingdom

PY - 2012

Y1 - 2012

N2 - 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

AB - 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

KW - Alzheimer's disease

KW - CLU

KW - CR1

KW - Genes

KW - Next generation sequencing

KW - PICALM

M3 - Article

C2 - 23205178

SN - 1948-1756

VL - 3

SP - 262

EP - 275

JO - International Journal of Molecular Epidemiology and Genetics

JF - International Journal of Molecular Epidemiology and Genetics

IS - 4

ER -

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

Abstract

Keywords

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