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

NEUROBIOLOGY OF AGING

卷:57

Article

Blauwendraat, Cornelis¹  Faghri, Faraz^2,3  Pihlstrom, Lasse^4,5,6  Geiger, Joshua T.¹  Elbaz, Alexis^7,8  Lesage, Suzanne⁹  Corvol, Jean-Christophe⁹  May, Patrick¹⁰  Nicolas, Aude²  Abramzon, Yevgeniya²  Murphy, Natalie A.²  Gibbs, J. Raphael²  Ryten, Mina⁴  Ferrari, Raffaele⁴  Bras, Jose⁴  Guerreiro, Rita⁴  Williams, Julie¹¹  Sims, Rebecca¹¹  Lubbe, Steven^12,13  Hernandez, Dena G.^2,14  Mok, Kin Y.¹⁵  Robak, Laurie¹⁶  Campbell, Roy H.¹⁷  Rogaeva, Ekaterina^17,18  Traynor, Bryan J.²  Chia, Ruth²  Chung, Sun Ju¹⁹  Hardy, John A.⁴  Brice, Alexis⁹  Wood, NicholasW.¹²  Houlden, Henry⁴  Shulman, Joshua M.^16,20  Morris, Huw R.¹²  Gasser, Thomas^14,20  Krueger, Rejko^10,21  Heutink, Peter^14,21  Sharma, Manu²²  Simon-Sanchez, Javier^14,21  Nalls, Mike A.^2,23  Singleton, Andrew B.²  Scholz, SonjaW.^1,24 

[1] NINDS, Neurodegenerat Dis Res Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[2] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA

[3] Univ Illinois, Dept Comp Sci, Urbana, IL USA

[4] UCL, Inst Neurol, Dept Mol Neurosci, London, England

[5] Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway

[6] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[7] Univ Paris Sud, Univ Paris Saclay, UVSQ, CESP,INSERM,U1018, Villejuif, France

[8] Sante Publ France, St Maurice, France

[9] UPMC Univ Paris 06, Sorbonne Univ, INSERM,U1127, Inst Cerveau & Moelle Epiniere,UMR S1127,ICM, Paris, France

[10] Univ Luxembourg, LCSB, Esch Sur Alzette, Luxembourg

[11] MRC, Ctr Neuropsychiat Genet & Genom, Div Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales

[12] UCL, Inst Neurol, Dept Clin Neurosci, London, England

[13] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL USA

[14] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[15] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China

[16] Baylor Coll Med, Dept Neurol, Houston, TX USA

[17] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[18] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada

[19] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea

[20] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

[21] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[22] Univ Tubingen, Inst Clin Epidemiol & Appl Biometry, Ctr Genet Epidemiol, Tubingen, Germany

[23] Data Tecn Int, Glen Echo, MD USA

[24] Johns Hopkins Univ, Med Ctr, Dept Neurol, Baltimore, MD 21218 USA

关键词: Genotyping;    NeuroX;    NeuroChip;    Genetic screening;    Neurodegeneration;   

DOI  :  10.1016/j.neurobiolaging.2017.05.009

来源: Elsevier

【 摘 要 】

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, costeffective screening tool for genetic research and molecular diagnostics in neurodegenerative diseases. Published by Elsevier Inc.

【 授权许可】

Free