A susceptibility gene for late-onset idiopathic Parkinson's disease
A susceptibility gene for late-onset idiopathic Parkinson's disease
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DOI：
10.1002/ana.10324
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发表时间：
2002-11-01
影响因子：
11.2
通讯作者：
Sveinbjörnsdóttir, S
中科院分区：
文献类型：
--
作者：
Hicks, AA;Pétursson, H;Sveinbjörnsdóttir, S
基因组的八个区域(PARK1-8)与常染色体显性遗传和常染色体隐性遗传的早发性帕金森病有关。这些形式构成了所有情况中的一小部分。然而，除了6个家系中的一个单倍型(Park3)，还没有研究成功地定位一个基因或描述导致常见的晚发性帕金森氏症的突变。一些人甚至提出，基因成分并不存在。我们将我们的全国家谱数据库与冰岛帕金森氏症患者的基于人群的名单进行交叉匹配，以搜索有不止一名患者的家庭。我们使用781个微卫星标记对51个家族中的117名患者及其168名未受影响的亲属进行了全基因组扫描。等位基因共享、模型无关分析结果显示与染色体1p32上的一个区域连锁，优势分数的对数为3.9(Z(LR)=4.2)。通过在该区域增加微卫星标记的信息量，我们发现优势分数的对数增加到4.9(Z(LR)=4.8)。这一结果对应于未调整的p值1.0x10(-6)和调整全基因组搜索后的p<；0.005。我们将这个地区命名为PARK10。因此，我们成功地绘制了具有全基因组意义的迟发性帕金森氏病的易感基因图谱，使用了横跨整个人群的多个家庭。识别该区域的易感基因可能为更好地了解疾病过程铺平道路，这反过来可能导致改进诊断和治疗。
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.