A susceptibility gene for late‐onset idiopathic Parkinson's disease
Identifieur interne : 001946 ( Main/Exploration ); précédent : 001945; suivant : 001947A susceptibility gene for late‐onset idiopathic Parkinson's disease
Auteurs : Andrew A. Hicks [Islande] ; Hjörvar Pétursson [Islande] ; Thorlákur J Nsson [Islande] ; Hreinn Stefánsson [Islande] ; Hrefna S. J Hannsd Ttir [Islande] ; Jesus Sainz [Islande] ; Michael L. Frigge [Islande] ; Augustine Kong [Islande] ; Jeffrey R. Gulcher [Islande] ; Kári Stefánsson [Islande] ; Sigurlaug Sveinbjörnsd Ttir [Islande]Source :
- Annals of Neurology [ 0364-5134 ] ; 2002-11.
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 (Zlr = 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 (Zlr = 4.8). This result corresponds to an unadjusted p value of 1.0 × 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.
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DOI: 10.1002/ana.10324
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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 (Zlr = 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 (Zlr = 4.8). This result corresponds to an unadjusted p value of 1.0 × 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.</div></front></TEI><affiliations><list><country><li>Islande</li></country></list><tree><country name="Islande"><noRegion><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A." last="Hicks">Andrew A. Hicks</name></noRegion><name sortKey="Frigge, Michael L" sort="Frigge, Michael L" uniqKey="Frigge M" first="Michael L." last="Frigge">Michael L. Frigge</name><name sortKey="Gulcher, Jeffrey R" sort="Gulcher, Jeffrey R" uniqKey="Gulcher J" first="Jeffrey R." last="Gulcher">Jeffrey R. Gulcher</name><name sortKey="J Hannsd Ttir, Hrefna S" sort="J Hannsd Ttir, Hrefna S" uniqKey="J Hannsd Ttir H" first="Hrefna S." last="J Hannsd Ttir">Hrefna S. J Hannsd Ttir</name><name sortKey="J Nsson, Thorlakur" sort="J Nsson, Thorlakur" uniqKey="J Nsson T" first="Thorlákur" last="J Nsson">Thorlákur J Nsson</name><name sortKey="Kong, Augustine" sort="Kong, Augustine" uniqKey="Kong A" first="Augustine" last="Kong">Augustine Kong</name><name sortKey="Petursson, Hjorvar" sort="Petursson, Hjorvar" uniqKey="Petursson H" first="Hjörvar" last="Pétursson">Hjörvar Pétursson</name><name sortKey="Sainz, Jesus" sort="Sainz, Jesus" uniqKey="Sainz J" first="Jesus" last="Sainz">Jesus Sainz</name><name sortKey="Stefansson, Hreinn" sort="Stefansson, Hreinn" uniqKey="Stefansson H" first="Hreinn" last="Stefánsson">Hreinn Stefánsson</name><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kári" last="Stefánsson">Kári Stefánsson</name><name sortKey="Sveinbjornsd Ttir, Sigurlaug" sort="Sveinbjornsd Ttir, Sigurlaug" uniqKey="Sveinbjornsd Ttir S" first="Sigurlaug" last="Sveinbjörnsd Ttir">Sigurlaug Sveinbjörnsd Ttir</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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