title: Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis.
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.
authors.affiliation: Reta Lila Weston Institute, UCL Institute of Neurology, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Reta Lila Weston Institute, UCL Institute of Neurology, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shoai
authors.affiliation: Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Sidle
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Orrell
authors.affiliation: Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Sweeney
authors.affiliation: Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Shatunov
authors.affiliation: Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Sproviero
authors.affiliation: Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Clinical Neuroscience, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.affiliation: Reta Lila Weston Institute, UCL Institute of Neurology, London, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: 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.
authors.forename: Alan
authors.initials: A
authors.lastname: Pittman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D015331:Cohort Studies; D059014:High-Throughput Nucleotide Sequencing / Q000191:economics / Q000379:methods* / Q000639:trends*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D015203:Reproducibility of Results
keywords: ALS; Amyotrophic lateral sclerosis; Diagnosis; Genetic; MiSeq; NGS; Neurogenetics; Next-generation sequencing; Sequencing