3.00
Hdl Handle:
http://hdl.handle.net/2336/31253
Title:
A susceptibility gene for late-onset idiopathic Parkinson's disease
Authors:
Hicks, Andrew A; Petursson, Hjorvar; Jonsson, Thorlakur; Stefansson, Hreinn; Johannsdottir, Hrefna S; Sainz, Jesus; Frigge, Michael L; Kong, Augustine; Gulcher, Jeffrey R; Stefansson, Kari; Sveinbjornsdóttir, Sigurlaug
Citation:
Ann. Neurol. 2002, 52(5):549-55
Issue Date:
1-Nov-2002
Abstract:
Eight regions of the genome (PARK1-8) have been implicated in autosomal dominant and autosomal recessive forms of early-onset Parkinson's disease. These forms constitute a few of all cases. However, except for a haplotype in six families (PARK3), no study has successfully mapped a gene or described mutations that contribute to the common late-onset Parkinson's disease. Some have even suggested that a genetic component does not exist. We cross-matched our nationwide genealogy database with a population-based list of Icelandic Parkinson's disease patients to search for families with more than one patient. We performed a genomewide scan on 117 patients and 168 of their unaffected relatives within 51 families using 781 microsatellite markers. Allele-sharing, model-independent analysis of the results showed linkage to a region on chromosome 1p32 with a logarithm of odds score of 3.9 (Z(lr) = 4.2). By increasing the information content with additional microsatellite markers in this region, we found that the logarithm of odds score increased to 4.9 (Z(lr) = 4.8). This result corresponds to an unadjusted p value of 1.0 x 10(-6) and p < 0.005 after adjusting for a genomewide search. We designate this region PARK10. We therefore have successfully mapped, to genomewide significance, a susceptibility gene for late-onset Parkinson's disease using multiple families drawn across a whole population. Identification of the susceptibility gene in this region may pave the way for a better understanding of the disease process, which, in turn, may lead to improved diagnostics and therapeutics.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1002/ana.10324

Full metadata record

DC FieldValue Language
dc.contributor.authorHicks, Andrew A-
dc.contributor.authorPetursson, Hjorvar-
dc.contributor.authorJonsson, Thorlakur-
dc.contributor.authorStefansson, Hreinn-
dc.contributor.authorJohannsdottir, Hrefna S-
dc.contributor.authorSainz, Jesus-
dc.contributor.authorFrigge, Michael L-
dc.contributor.authorKong, Augustine-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorStefansson, Kari-
dc.contributor.authorSveinbjornsdóttir, Sigurlaug-
dc.date.accessioned2008-07-08T11:31:24Z-
dc.date.available2008-07-08T11:31:24Z-
dc.date.issued2002-11-01-
dc.date.submitted2008-07-08-
dc.identifier.citationAnn. Neurol. 2002, 52(5):549-55en
dc.identifier.issn0364-5134-
dc.identifier.pmid12402251-
dc.identifier.doi10.1002/ana.10324-
dc.identifier.urihttp://hdl.handle.net/2336/31253-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractEight regions of the genome (PARK1-8) have been implicated in autosomal dominant and autosomal recessive forms of early-onset Parkinson's disease. These forms constitute a few of all cases. However, except for a haplotype in six families (PARK3), no study has successfully mapped a gene or described mutations that contribute to the common late-onset Parkinson's disease. Some have even suggested that a genetic component does not exist. We cross-matched our nationwide genealogy database with a population-based list of Icelandic Parkinson's disease patients to search for families with more than one patient. We performed a genomewide scan on 117 patients and 168 of their unaffected relatives within 51 families using 781 microsatellite markers. Allele-sharing, model-independent analysis of the results showed linkage to a region on chromosome 1p32 with a logarithm of odds score of 3.9 (Z(lr) = 4.2). By increasing the information content with additional microsatellite markers in this region, we found that the logarithm of odds score increased to 4.9 (Z(lr) = 4.8). This result corresponds to an unadjusted p value of 1.0 x 10(-6) and p < 0.005 after adjusting for a genomewide search. We designate this region PARK10. We therefore have successfully mapped, to genomewide significance, a susceptibility gene for late-onset Parkinson's disease using multiple families drawn across a whole population. Identification of the susceptibility gene in this region may pave the way for a better understanding of the disease process, which, in turn, may lead to improved diagnostics and therapeutics.en
dc.language.isoenen
dc.publisherWiley-Lissen
dc.relation.urlhttp://dx.doi.org/10.1002/ana.10324en
dc.subject.meshAge of Onseten
dc.subject.meshAgeden
dc.subject.meshAllelesen
dc.subject.meshChromosome Mappingen
dc.subject.meshChromosomes, Human, Pair 1en
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome, Humanen
dc.subject.meshHumansen
dc.subject.meshLinkage (Genetics)en
dc.subject.meshLod Scoreen
dc.subject.meshMaleen
dc.subject.meshMicrosatellite Repeatsen
dc.subject.meshParkinson Diseaseen
dc.subject.meshPedigreeen
dc.titleA susceptibility gene for late-onset idiopathic Parkinson's diseaseen
dc.typeArticleen
dc.contributor.departmentdeCODE Genetics, Sturlogötu 8, Reykjavik 101, Iceland.en
dc.identifier.journalAnnals of neurologyen

Related articles on PubMed

All Items in Hirsla are protected by copyright, with all rights reserved, unless otherwise indicated.