Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

Ahmad Al Khleifat; Alfredo Iacoangeli; Ashley Jones; Joke van Vugt; Aleksey Shatunov; Matthieu Moisse; Aleksey Shatunov; Ramona A.J. Zwamborn; Rick van der Spek; Johnathan Cooper-Knock; Simon Topp; Wouter van Rheenen; Brendan J Kenna; Kristel R. van Eijk; Kevin P Kenna; Ross P. Byrne; Victoria  López Alonso; Sarah Opie-Martin; Atay  Vural; Yolanda  González; Markus Weber; Bradley Smith; Isabella Fogh; Vincenzo Silani; Karen E. Morrison; Richard Dobson; Michael A. van Es; Russell L. McLaughlin; Adriano Chio; Philippe Corcia; Mamede de Carvalho; Marc Gotkine; Monica P. Panades; Jesus S Mora; Pamela J. Shaw; John E. Landers; Jonathan D. Glass; Christopher Shaw; A. Nazli Başak; Orla Hardiman; Wim Robberecht; Philip Van Damme; Leonard van den Berg; Jan Veldink; Ammar Al-Chalabi

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

Ahmad Al Khleifat, Alfredo Iacoangeli, Ashley Jones, Joke van Vugt, Aleksey Shatunov, Matthieu Moisse, Aleksey Shatunov, Ramona A.J. Zwamborn, Rick van der Spek, Johnathan Cooper-Knock, Simon Topp, Wouter van Rheenen, Brendan J Kenna, Kristel R. van Eijk, Kevin P Kenna, Ross P. Byrne, Victoria López Alonso, Sarah Opie-Martin, Atay Vural, Yolanda GonzálezMarkus Weber, Bradley Smith, Isabella Fogh, Vincenzo Silani, Karen E. Morrison, Richard Dobson, Michael A. van Es, Russell L. McLaughlin, Adriano Chio, Philippe Corcia, Mamede de Carvalho, Marc Gotkine, Monica P. Panades, Jesus S Mora, Pamela J. Shaw, John E. Landers, Jonathan D. Glass, Christopher Shaw, A. Nazli Başak, Orla Hardiman, Wim Robberecht, Philip Van Damme, Leonard van den Berg, Jan Veldink, Ammar Al-Chalabi

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Abstract

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, is a complex genetic disease with heritability
of 60%. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important, in addition to the known risk factors, male sex and increasing age. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. We find that longer telomeres are associated with ALS and specific phenotypic patterns of disease expression. We see the same pattern of telomere elongation in ALS in brain tissue. The association of longer telomeres with apparently sporadic ALS was also seen in people with familial ALS, supporting the notion that sporadic and familial ALS are not mutually exclusive categories but rather a spectrum.

Original language	English
Journal	Frontiers in cellular neuroscience
Publication status	Published - 15 Nov 2022

Keywords

Amyotrophic Lateral Sclerosis (ALS)
Telomere
genetics
Whole genome sequence (WGS
Genomics
Big Data
bioinforamtics

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Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data
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Accepted author manuscript, 390 KBLicence: Other

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Al Khleifat, A., Iacoangeli, A., Jones, A., van Vugt, J., Shatunov, A., Moisse, M., Shatunov, A., Zwamborn, R. A. J., van der Spek, R., Cooper-Knock, J., Topp, S., van Rheenen, W., Kenna, B. J., van Eijk, K. R., Kenna, K. P., Byrne, R. P., López Alonso, V., Opie-Martin, S., Vural, A., ... Al-Chalabi, A. (2022). Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data. Frontiers in cellular neuroscience.

@article{6afe467993e9415ba5b47e554a4b1a5c,

title = "Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data",

abstract = "Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, is a complex genetic disease with heritabilityof 60%. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important, in addition to the known risk factors, male sex and increasing age. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. We find that longer telomeres are associated with ALS and specific phenotypic patterns of disease expression. We see the same pattern of telomere elongation in ALS in brain tissue. The association of longer telomeres with apparently sporadic ALS was also seen in people with familial ALS, supporting the notion that sporadic and familial ALS are not mutually exclusive categories but rather a spectrum.",

keywords = "Amyotrophic Lateral Sclerosis (ALS), Telomere, genetics, Whole genome sequence (WGS, Genomics, Big Data, bioinforamtics",

author = "{Al Khleifat}, Ahmad and Alfredo Iacoangeli and Ashley Jones and {van Vugt}, Joke and Aleksey Shatunov and Matthieu Moisse and Aleksey Shatunov and Zwamborn, {Ramona A.J.} and {van der Spek}, Rick and Johnathan Cooper-Knock and Simon Topp and {van Rheenen}, Wouter and Kenna, {Brendan J} and {van Eijk}, {Kristel R.} and Kenna, {Kevin P} and Byrne, {Ross P.} and {L{\'o}pez Alonso}, Victoria and Sarah Opie-Martin and Atay Vural and Yolanda Gonz{\'a}lez and Markus Weber and Bradley Smith and Isabella Fogh and Vincenzo Silani and Morrison, {Karen E.} and Richard Dobson and {van Es}, {Michael A.} and McLaughlin, {Russell L.} and Adriano Chio and Philippe Corcia and {de Carvalho}, Mamede and Marc Gotkine and Panades, {Monica P.} and Mora, {Jesus S} and Shaw, {Pamela J.} and Landers, {John E.} and Glass, {Jonathan D.} and Christopher Shaw and Ba{\c s}ak, {A. Nazli} and Orla Hardiman and Wim Robberecht and {Van Damme}, Philip and {van den Berg}, Leonard and Jan Veldink and Ammar Al-Chalabi",

year = "2022",

month = nov,

day = "15",

language = "English",

journal = "Frontiers in cellular neuroscience",

issn = "1662-5102",

publisher = "Frontiers Media S.A.",

}

Al Khleifat, A , Iacoangeli, A , Jones, A, van Vugt, J, Shatunov, A, Moisse, M, Shatunov, A, Zwamborn, RAJ, van der Spek, R, Cooper-Knock, J, Topp, S, van Rheenen, W, Kenna, BJ, van Eijk, KR, Kenna, KP, Byrne, RP, López Alonso, V, Opie-Martin, S, Vural, A, González, Y, Weber, M, Smith, B , Fogh, I, Silani, V, Morrison, KE, Dobson, R, van Es, MA, McLaughlin, RL, Chio, A, Corcia, P, de Carvalho, M, Gotkine, M, Panades, MP, Mora, JS, Shaw, PJ, Landers, JE, Glass, JD, Shaw, C, Başak, AN, Hardiman, O, Robberecht, W, Van Damme, P, van den Berg, L, Veldink, J & Al-Chalabi, A 2022, 'Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data', Frontiers in cellular neuroscience.

TY - JOUR

T1 - Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

AU - Al Khleifat, Ahmad

AU - Iacoangeli, Alfredo

AU - Jones, Ashley

AU - van Vugt, Joke

AU - Shatunov, Aleksey

AU - Moisse, Matthieu

AU - Shatunov, Aleksey

AU - Zwamborn, Ramona A.J.

AU - van der Spek, Rick

AU - Cooper-Knock, Johnathan

AU - Topp, Simon

AU - van Rheenen, Wouter

AU - Kenna, Brendan J

AU - van Eijk, Kristel R.

AU - Kenna, Kevin P

AU - Byrne, Ross P.

AU - López Alonso, Victoria

AU - Opie-Martin, Sarah

AU - Vural, Atay

AU - González, Yolanda

AU - Weber, Markus

AU - Smith, Bradley

AU - Fogh, Isabella

AU - Silani, Vincenzo

AU - Morrison, Karen E.

AU - Dobson, Richard

AU - van Es, Michael A.

AU - McLaughlin, Russell L.

AU - Chio, Adriano

AU - Corcia, Philippe

AU - de Carvalho, Mamede

AU - Gotkine, Marc

AU - Panades, Monica P.

AU - Mora, Jesus S

AU - Shaw, Pamela J.

AU - Landers, John E.

AU - Glass, Jonathan D.

AU - Shaw, Christopher

AU - Başak, A. Nazli

AU - Hardiman, Orla

AU - Robberecht, Wim

AU - Van Damme, Philip

AU - van den Berg, Leonard

AU - Veldink, Jan

AU - Al-Chalabi, Ammar

PY - 2022/11/15

Y1 - 2022/11/15

N2 - Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, is a complex genetic disease with heritabilityof 60%. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important, in addition to the known risk factors, male sex and increasing age. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. We find that longer telomeres are associated with ALS and specific phenotypic patterns of disease expression. We see the same pattern of telomere elongation in ALS in brain tissue. The association of longer telomeres with apparently sporadic ALS was also seen in people with familial ALS, supporting the notion that sporadic and familial ALS are not mutually exclusive categories but rather a spectrum.

AB - Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of motor neurons, is a complex genetic disease with heritabilityof 60%. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important, in addition to the known risk factors, male sex and increasing age. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. We find that longer telomeres are associated with ALS and specific phenotypic patterns of disease expression. We see the same pattern of telomere elongation in ALS in brain tissue. The association of longer telomeres with apparently sporadic ALS was also seen in people with familial ALS, supporting the notion that sporadic and familial ALS are not mutually exclusive categories but rather a spectrum.

KW - Amyotrophic Lateral Sclerosis (ALS)

KW - Telomere

KW - genetics

KW - Whole genome sequence (WGS

KW - Genomics

KW - Big Data

KW - bioinforamtics

M3 - Article

SN - 1662-5102

JO - Frontiers in cellular neuroscience

JF - Frontiers in cellular neuroscience

ER -

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

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Keywords

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