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A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK

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A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK. / Morgan, Sarah; Shatunov, Aleksey; Sproviero, William; Jones, Ashley R; Shoai, Maryam; Hughes, Deborah; Al Khleifat, Ahmad; Malaspina, Andrea; Morrison, Karen E; Shaw, Pamela J; Shaw, Christopher E; Sidle, Katie; Orrell, Richard W; Fratta, Pietro; Hardy, John; Pittman, Alan; Al-Chalabi, Ammar.

In: Brain : a journal of neurology, Vol. 140, No. 6, 01.06.2017, p. 1611-1618.

Research output: Contribution to journalArticle

Harvard

Morgan, S, Shatunov, A, Sproviero, W, Jones, AR, Shoai, M, Hughes, D, Al Khleifat, A, Malaspina, A, Morrison, KE, Shaw, PJ, Shaw, CE, Sidle, K, Orrell, RW, Fratta, P, Hardy, J, Pittman, A & Al-Chalabi, A 2017, 'A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK', Brain : a journal of neurology, vol. 140, no. 6, pp. 1611-1618. https://doi.org/10.1093/brain/awx082

APA

Morgan, S., Shatunov, A., Sproviero, W., Jones, A. R., Shoai, M., Hughes, D., ... Al-Chalabi, A. (2017). A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK. Brain : a journal of neurology, 140(6), 1611-1618. https://doi.org/10.1093/brain/awx082

Vancouver

Morgan S, Shatunov A, Sproviero W, Jones AR, Shoai M, Hughes D et al. A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK. Brain : a journal of neurology. 2017 Jun 1;140(6):1611-1618. https://doi.org/10.1093/brain/awx082

Author

Morgan, Sarah ; Shatunov, Aleksey ; Sproviero, William ; Jones, Ashley R ; Shoai, Maryam ; Hughes, Deborah ; Al Khleifat, Ahmad ; Malaspina, Andrea ; Morrison, Karen E ; Shaw, Pamela J ; Shaw, Christopher E ; Sidle, Katie ; Orrell, Richard W ; Fratta, Pietro ; Hardy, John ; Pittman, Alan ; Al-Chalabi, Ammar. / A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK. In: Brain : a journal of neurology. 2017 ; Vol. 140, No. 6. pp. 1611-1618.

Bibtex Download

@article{80c9613923e14da88c492f9fda248103,
title = "A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK",
abstract = "Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10{\%} of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1{\%}) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis.",
keywords = "Journal Article",
author = "Sarah Morgan and Aleksey Shatunov and William Sproviero and Jones, {Ashley R} and Maryam Shoai and Deborah Hughes and {Al Khleifat}, Ahmad and Andrea Malaspina and Morrison, {Karen E} and Shaw, {Pamela J} and Shaw, {Christopher E} and Katie Sidle and Orrell, {Richard W} and Pietro Fratta and John Hardy and Alan Pittman and Ammar Al-Chalabi",
note = "{\circledC} The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.",
year = "2017",
month = "6",
day = "1",
doi = "10.1093/brain/awx082",
language = "English",
volume = "140",
pages = "1611--1618",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "6",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK

AU - Morgan, Sarah

AU - Shatunov, Aleksey

AU - Sproviero, William

AU - Jones, Ashley R

AU - Shoai, Maryam

AU - Hughes, Deborah

AU - Al Khleifat, Ahmad

AU - Malaspina, Andrea

AU - Morrison, Karen E

AU - Shaw, Pamela J

AU - Shaw, Christopher E

AU - Sidle, Katie

AU - Orrell, Richard W

AU - Fratta, Pietro

AU - Hardy, John

AU - Pittman, Alan

AU - Al-Chalabi, Ammar

N1 - © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis.

AB - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis.

KW - Journal Article

U2 - 10.1093/brain/awx082

DO - 10.1093/brain/awx082

M3 - Article

C2 - 28430856

VL - 140

SP - 1611

EP - 1618

JO - Brain

JF - Brain

SN - 0006-8950

IS - 6

ER -

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