File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration

TitleVariants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2009, v. 18 n. 3, p. 472-481 How to Cite?
AbstractAmyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P = 1.96 × 10-9). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P = 0.83 × 10-12 (start codon morpholino) and -0.46, P = 4.05 × 10-9 (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P = 0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS. © 2008 The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/59729
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
Funding AgencyGrant Number
Medical Research Council (UK)
Motor Neurone Disease Association
University of Leuven
Belgian government
Howard Hughes Medical Institute
The National Institutes of Neurological Disease and Stroke
National Institute on Aging
Al-Athel ALS Research Foundation
ALS Therapy Alliance
ALS Research Foundation
Medical Research Council (MRC) Clinician Scientist Fellow
GKT PhD Studentship
Marie Curie Excellence Grant
Medical Research Council
Funding Information:

This work was supported by the Medical Research Council (UK) to A.A.-C.; ALS Association to A.A.-C. and R. H. B.; Motor Neurone Disease Association to A.A.-C.; University of Leuven to W. R.; the Belgian government (Interuniversity Attraction Poles Programme 6/43-Belgian State-Belgian Science Policy) to W.R.; VIB to W.R. and P.V.; the Robert Packard Center for ALS Research to W.R.; the Howard Hughes Medical Institute to H.R.H.; The National Institutes of Neurological Disease and Stroke to R.H.B.; the National Institute on Aging to R.H.B.; the Al-Athel ALS Research Foundation to R.H.B.; the ALS Therapy Alliance to R.H.B., the Angel Fund to R.H.B.; Project ALS to R.H.B.; and the Pierre L. de Bourgknecht ALS Research Foundation to R. H. B. For much of this work, A.A.-C. was a Medical Research Council (MRC) Clinician Scientist Fellow and C.L.S. was funded by GKT PhD Studentship. P. S. and H.R.H. were supported by the Howard Hughes Medical Institute. W.R. was supported through the Evon Behring Chair for Neuromuscular and Neurodegenerative Disorders. P.V. was supported through a Marie Curie Excellence Grant. Funding to pay the Open Access Charge was provided by the Medical Research Council.

References

 

DC FieldValueLanguage
dc.contributor.authorSimpson, CLen_HK
dc.contributor.authorLemmens, Ren_HK
dc.contributor.authorMiskiewicz, Ken_HK
dc.contributor.authorBroom, WJen_HK
dc.contributor.authorHansen, VKen_HK
dc.contributor.authorvan Vught, PWJen_HK
dc.contributor.authorLanders, JEen_HK
dc.contributor.authorSapp, Pen_HK
dc.contributor.authorvan Den Bosch, Len_HK
dc.contributor.authorKnight, Jen_HK
dc.contributor.authorNeale, BMen_HK
dc.contributor.authorTurner, MRen_HK
dc.contributor.authorVeldink, JHen_HK
dc.contributor.authorOphoff, RAen_HK
dc.contributor.authorTripathi, VBen_HK
dc.contributor.authorBeleza, Aen_HK
dc.contributor.authorShah, MNen_HK
dc.contributor.authorProitsi, Pen_HK
dc.contributor.authorVan Hoecke, Aen_HK
dc.contributor.authorCarmeliet, Pen_HK
dc.contributor.authorHorvitz, HRen_HK
dc.contributor.authorLeigh, PNen_HK
dc.contributor.authorShaw, CEen_HK
dc.contributor.authorvan den Berg, LHen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorPowell, JFen_HK
dc.contributor.authorVerstreken, Pen_HK
dc.contributor.authorBrown Jr, RHen_HK
dc.contributor.authorRobberecht, Wen_HK
dc.contributor.authorAlChalabi, Aen_HK
dc.date.accessioned2010-05-31T03:56:13Z-
dc.date.available2010-05-31T03:56:13Z-
dc.date.issued2009en_HK
dc.identifier.citationHuman Molecular Genetics, 2009, v. 18 n. 3, p. 472-481en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59729-
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P = 1.96 × 10-9). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P = 0.83 × 10-12 (start codon morpholino) and -0.46, P = 4.05 × 10-9 (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P = 0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS. © 2008 The Author(s).en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
dc.rightsHuman Molecular Genetics. Copyright © Oxford University Press.en_HK
dc.titleVariants of the elongator protein 3 (ELP3) gene are associated with motor neuron degenerationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0964-6906&volume=18 &issue=3&spage=472&epage=481&date=2009&atitle=Variants+of+the+elongator+protein+3+(ELP3)+gene+are+associated+with+motor+neuron+degenerationen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/hmg/ddn375en_HK
dc.identifier.pmid18996918-
dc.identifier.scopuseid_2-s2.0-58749097964en_HK
dc.identifier.hkuros158180en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58749097964&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue3en_HK
dc.identifier.spage472en_HK
dc.identifier.epage481en_HK
dc.identifier.isiWOS:000262519300008-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSimpson, CL=12789397500en_HK
dc.identifier.scopusauthoridLemmens, R=16039704900en_HK
dc.identifier.scopusauthoridMiskiewicz, K=24780807000en_HK
dc.identifier.scopusauthoridBroom, WJ=10139457000en_HK
dc.identifier.scopusauthoridHansen, VK=7102356948en_HK
dc.identifier.scopusauthoridvan Vught, PWJ=9435619400en_HK
dc.identifier.scopusauthoridLanders, JE=7103347073en_HK
dc.identifier.scopusauthoridSapp, P=35394708400en_HK
dc.identifier.scopusauthoridvan Den Bosch, L=7005171888en_HK
dc.identifier.scopusauthoridKnight, J=13002769800en_HK
dc.identifier.scopusauthoridNeale, BM=7003484514en_HK
dc.identifier.scopusauthoridTurner, MR=7403215612en_HK
dc.identifier.scopusauthoridVeldink, JH=6603240539en_HK
dc.identifier.scopusauthoridOphoff, RA=7004321340en_HK
dc.identifier.scopusauthoridTripathi, VB=36789394600en_HK
dc.identifier.scopusauthoridBeleza, A=36943897500en_HK
dc.identifier.scopusauthoridShah, MN=36876431900en_HK
dc.identifier.scopusauthoridProitsi, P=23035958100en_HK
dc.identifier.scopusauthoridVan Hoecke, A=24069659800en_HK
dc.identifier.scopusauthoridCarmeliet, P=7101979069en_HK
dc.identifier.scopusauthoridHorvitz, HR=7007006983en_HK
dc.identifier.scopusauthoridLeigh, PN=26643325600en_HK
dc.identifier.scopusauthoridShaw, CE=35370282000en_HK
dc.identifier.scopusauthoridvan den Berg, LH=7101946205en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridPowell, JF=7403541196en_HK
dc.identifier.scopusauthoridVerstreken, P=6602697545en_HK
dc.identifier.scopusauthoridBrown Jr, RH=36077481100en_HK
dc.identifier.scopusauthoridRobberecht, W=7005572606en_HK
dc.identifier.scopusauthoridAlChalabi, A=7003751621en_HK
dc.identifier.citeulike4247091-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats