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.
| Original language | English |
|---|---|
| Journal | Neurobiology of Aging |
| Volume | 57 |
| Pages (from-to) | 247.e9-247.e13 |
| ISSN | 0197-4580 |
| DOIs | |
| Publication status | Published - 01.09.2017 |
Funding
The authors would like to thank all of the subjects who donated their time and biological samples to be a part of this study. NABEC control brain tissues were obtained from the Baltimore Longitudinal Study on Aging at the Johns Hopkins School of Medicine, and from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. This work was supported in part by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), and the National Institute of Environmental Health Sciences both part of the National Institutes of Health, Department of Health and Human Services; project numbers Z01-AG000949-02, Z01-ES101986, 1ZIANS003154. Faraz Faghri's contribution to this work has been supported in part through the grant 1U54GM114838 awarded by NIGMS through funds provided by the trans-NIH big data to Knowledge (BD2K) initiative (www.bd2k.nih.gov/). The project underlying this publication was funded by the German Federal Ministry of Education and Research under the support code 031 A 430 A. Responsibility for the content lies with the authors. The project was also supported through the following funding organizations under the aegis of the EU Joint Programme for Neurodegenerative Disease Research (JPND; www.jpnd.eu). This study was also supported by Parkinson's UK (grants 8047 and J-0804) and the Medical Research Council (G0700943 and G1100643). Joshua M. Shulman is supported by the Huffington Foundation and a Career Award for Medical Scientists from the Burroughs Wellcome Fund.