Identification of Risk and Age-at-Onset Genes on Chromosome 1p in Parkinson Disease
Identifieur interne : 001028 ( Main/Curation ); précédent : 001027; suivant : 001029Identification of Risk and Age-at-Onset Genes on Chromosome 1p in Parkinson Disease
Auteurs : Sofia Oliveira ; Yi Li ; Maher Noureddine ; Stephan Züchner ; Xuejun Qin ; Margaret Pericak ; Jeffery VanceSource :
- American Journal of Human Genetics [ 0002-9297 ] ; 2005.
Abstract
We previously reported a linkage region on chromosome 1p (LOD = 3.41) for genes controlling age at onset (AAO) in Parkinson disease (PD). This region overlaps with the previously reported
Url:
PubMed: 15986317
PubMed Central: 1224528
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PMC:1224528Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of Risk and Age-at-Onset Genes on Chromosome 1p in Parkinson Disease</title>
<author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name>
</author>
<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
</author>
<author><name sortKey="Noureddine, Maher A" sort="Noureddine, Maher A" uniqKey="Noureddine M" first="Maher" last="Noureddine">Maher Noureddine</name>
</author>
<author><name sortKey="Zuchner, Stephan" sort="Zuchner, Stephan" uniqKey="Zuchner S" first="Stephan" last="Züchner">Stephan Züchner</name>
</author>
<author><name sortKey="Qin, Xuejun" sort="Qin, Xuejun" uniqKey="Qin X" first="Xuejun" last="Qin">Xuejun Qin</name>
</author>
<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of Risk and Age-at-Onset Genes on Chromosome 1p in Parkinson Disease</title>
<author><name sortKey="Oliveira, Sofia A" sort="Oliveira, Sofia A" uniqKey="Oliveira S" first="Sofia" last="Oliveira">Sofia Oliveira</name>
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<author><name sortKey="Li, Yi Ju" sort="Li, Yi Ju" uniqKey="Li Y" first="Yi" last="Li">Yi Li</name>
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<author><name sortKey="Noureddine, Maher A" sort="Noureddine, Maher A" uniqKey="Noureddine M" first="Maher" last="Noureddine">Maher Noureddine</name>
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<author><name sortKey="Zuchner, Stephan" sort="Zuchner, Stephan" uniqKey="Zuchner S" first="Stephan" last="Züchner">Stephan Züchner</name>
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<author><name sortKey="Qin, Xuejun" sort="Qin, Xuejun" uniqKey="Qin X" first="Xuejun" last="Qin">Xuejun Qin</name>
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<author><name sortKey="Pericak Vance, Margaret A" sort="Pericak Vance, Margaret A" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
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<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
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<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="e-ISSN">1537-6605</idno>
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<front><div type="abstract" xml:lang="en"><p>We previously reported a linkage region on chromosome 1p (LOD = 3.41) for genes controlling age at onset (AAO) in Parkinson disease (PD). This region overlaps with the previously reported <italic>PARK10</italic>
locus. To identify the gene(s) associated with AAO and risk of PD in this region, we first applied a genomic convergence approach that combined gene expression and linkage data. No significant results were found. Second, we performed association mapping across a 19.2-Mb region centered under the AAO linkage peak. An iterative association mapping approach was done by initially genotyping single-nucleotide polymorphisms at an average distance of 100 kb apart and then by increasing the density of markers as needed. Using the overall data set of 267 multiplex families, we identified six associated genes in the region, but further screening of a subset of 83 families linked to the chromosome 1 locus identified only two genes significantly associated with AAO in PD: the γ subunit of the translation initiation factor EIF2B gene (<italic>EIF2B3</italic>
), which was more significant in the linked subset and the ubiquitin-specific protease 24 gene (<italic>USP24</italic>
). Unexpectedly, the human immunodeficiency virus enhancer-binding protein 3 gene (<italic>HIVEP3</italic>
) was found to be associated with risk for susceptibility to PD. We used several criteria to define significant results in the presence of multiple testing, including criteria derived from a novel cluster approach. The known or putative functions of these genes fit well with the current suspected pathogenic mechanisms of PD and thus show great potential as candidates for the <italic>PARK10</italic>
locus.</p>
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