. 2017 Sep:57:247.e9-247.e13.

doi: 10.1016/j.neurobiolaging.2017.05.009. Epub 2017 May 17.

NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Cornelis Blauwendraat¹, Faraz Faghri², Lasse Pihlstrom³, Joshua T Geiger¹, Alexis Elbaz⁴, Suzanne Lesage⁵, Jean-Christophe Corvol⁵, Patrick May⁶, Aude Nicolas⁷, Yevgeniya Abramzon⁷, Natalie A Murphy⁷, J Raphael Gibbs⁷, Mina Ryten⁸, Raffaele Ferrari⁸, Jose Bras⁸, Rita Guerreiro⁸, Julie Williams⁹, Rebecca Sims⁹, Steven Lubbe¹⁰, Dena G Hernandez¹¹, Kin Y Mok¹², Laurie Robak¹³, Roy H Campbell¹⁴, Ekaterina Rogaeva¹⁵, Bryan J Traynor⁷, Ruth Chia⁷, Sun Ju Chung¹⁶; International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium; John A Hardy⁸, Alexis Brice⁵, Nicholas W Wood¹⁷, Henry Houlden⁸, Joshua M Shulman¹⁸, Huw R Morris¹⁷, Thomas Gasser¹⁹, Rejko Krüger²⁰, Peter Heutink²¹, Manu Sharma²², Javier Simón-Sánchez²¹, Mike A Nalls²³, Andrew B Singleton⁷, Sonja W Scholz²⁴

Affiliations

¹ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
³ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁴ Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM-U1018, Villejuif, France; Santé publique France, Saint-Maurice, France.
⁵ Inserm U1127, Sorbonne Universités, UPMC Univ Paris 06 UMR S1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
⁶ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg.
⁷ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁸ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
⁹ Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
¹⁰ Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
¹² Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, China.
¹³ Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
¹⁴ Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁵ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
¹⁷ Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
¹⁸ Department of Neurology, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
¹⁹ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
²⁰ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
²¹ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
²² Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Centre for Genetic Epidemiology, Institute of Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
²³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
²⁴ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA. Electronic address: sonja.scholz@nih.gov.

PMID: 28602509
PMCID: PMC5534378
DOI: 10.1016/j.neurobiolaging.2017.05.009

NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

Cornelis Blauwendraat et al. Neurobiol Aging. 2017 Sep.

. 2017 Sep:57:247.e9-247.e13.

doi: 10.1016/j.neurobiolaging.2017.05.009. Epub 2017 May 17.

Authors

Affiliations

¹ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
³ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁴ Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM-U1018, Villejuif, France; Santé publique France, Saint-Maurice, France.
⁵ Inserm U1127, Sorbonne Universités, UPMC Univ Paris 06 UMR S1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
⁶ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg.
⁷ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁸ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
⁹ Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
¹⁰ Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
¹² Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, China.
¹³ Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
¹⁴ Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁵ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
¹⁷ Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
¹⁸ Department of Neurology, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
¹⁹ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
²⁰ Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
²¹ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
²² Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Centre for Genetic Epidemiology, Institute of Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
²³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
²⁴ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA. Electronic address: sonja.scholz@nih.gov.

PMID: 28602509
PMCID: PMC5534378
DOI: 10.1016/j.neurobiolaging.2017.05.009

Abstract

Genetics has proven to be a powerful approach in neurodegenerative diseases research, resulting in the identification of numerous causal and risk variants. Previously, we introduced the NeuroX Illumina genotyping array, a fast and efficient genotyping platform designed for the investigation of genetic variation in neurodegenerative diseases. Here, we present its updated version, named NeuroChip. The NeuroChip is a low-cost, custom-designed array containing a tagging variant backbone of about 306,670 variants complemented with a manually curated custom content comprised of 179,467 variants implicated in diverse neurological diseases, including Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy. The tagging backbone was chosen because of the low cost and good genome-wide resolution; the custom content can be combined with other backbones, like population or drug development arrays. Using the NeuroChip, we can accurately identify rare variants and impute over 5.3 million common SNPs from the latest release of the Haplotype Reference Consortium. In summary, we describe the design and usage of the NeuroChip array and show its capability for detecting rare pathogenic variants in numerous neurodegenerative diseases. The NeuroChip has a more comprehensive and improved content, which makes it a reliable, high-throughput, cost-effective screening tool for genetic research and molecular diagnostics in neurodegenerative diseases.

Keywords: Genetic screening; Genotyping; NeuroChip; NeuroX; Neurodegeneration.

Published by Elsevier Inc.

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Figures

**Figure 1. Overview of the number of HGMD disease associated variants that are present on the NeuroChip**
AD = Alzheimer's disease, ALS = amyotrophic lateral sclerosis, FTD = frontotemporal dementia, and PD = Parkinson's disease

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NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

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NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases

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