Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis

Sarah Morgan; Maryam Shoai; Pietro Fratta; Katie Sidle; Richard Orrell; Mary G Sweeney; Aleksey Shatunov; William Sproviero; Ashley Jones; Ammar Al-Chalabi; Andrea Malaspina; Henry Houlden; John Hardy; Alan Pittman

doi:10.1016/j.neurobiolaging.2014.12.017

Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis

Neurobiol Aging. 2015 Mar;36(3):1600.e5-8. doi: 10.1016/j.neurobiolaging.2014.12.017. Epub 2014 Dec 20.

Authors

Affiliations

¹ Reta Lila Weston Institute, UCL Institute of Neurology, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
² Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.
³ Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
⁴ Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, UK.
⁵ Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
⁶ Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, North-East London and Essex Regional Motor Neuron Disease Care Centre, London, UK.
⁷ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
⁸ Reta Lila Weston Institute, UCL Institute of Neurology, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. Electronic address: a.pittman@ucl.ac.uk.

PMID: 25588603
DOI: 10.1016/j.neurobiolaging.2014.12.017

Abstract

The future of genetic diagnostics will see a move toward massively parallel next-generation sequencing of a patient's DNA. Amyotrophic lateral sclerosis (ALS) is one of the diseases that would benefit from this prospect. Exploring this idea, we designed a screening panel to sequence 25 ALS-linked genes and examined samples from 95 patients with both familial and sporadic ALS. Forty-three rare polymorphisms were detected in this cohort. A third of these have already been reported with respect to ALS, leaving 28 novel variants all open for further investigation. This study highlights the potential benefits of next-generation sequencing as a reliable, cost and time efficient, diagnostic, and research tool for ALS.

Keywords: ALS; Amyotrophic lateral sclerosis; Diagnosis; Genetic; MiSeq; NGS; Neurogenetics; Next-generation sequencing; Sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / diagnosis*
Amyotrophic Lateral Sclerosis / genetics*
Cohort Studies
High-Throughput Nucleotide Sequencing / economics
High-Throughput Nucleotide Sequencing / methods*
High-Throughput Nucleotide Sequencing / trends*
Humans
Polymorphism, Genetic / genetics
Reproducibility of Results

Abstract

Publication types

MeSH terms

Grants and funding