Complete genomic screen in parkinson disease - Evidence for multiple genes
Complete genomic screen in parkinson disease - Evidence for multiple genes
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DOI：
10.1001/jama.286.18.2239
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发表时间：
2001-11-14
影响因子：
120.7
通讯作者：
Pericak-Vance, MA
中科院分区：
文献类型：
--
作者：
Scott, WK;Nance, MA;Pericak-Vance, MA
背景基因与环境在特发性帕金森病（PD）中的相对作用是有争议的。虽然遗传学研究已经确定了2个基因的突变导致罕见的单基因变异的PD和观察性研究提出了遗传成分，双胞胎研究表明，很少的遗传贡献存在于常见形式的PD。1995年至2000年进行的遗传连锁研究，（n=344个标志物）在174个家庭中进行了检测，其中有多个人被诊断患有特发性PD，通过美国大陆和澳大利亚13个临床人群的先证者确定。共有870名家庭成员接受了研究：378例诊断为PD，379例未受PD影响，结果两点参数最大参数lod得分（MLOD）和多点非参数lod得分（LOD）分别为113例和113例，两点参数最大参数lod得分（MLOD）和多点非参数lod得分（LOD）分别为113例和113例，两点参数最大参数lod得分（MLOD）和多点非参数lod得分（LOD）分别为113例和113例。连锁分析发现了与5个不同染色体区域连锁的重要证据：parkin基因中的6号染色体（MLOD = 5.07; LOD，= 5.47）在至少有1例PD发病年龄小于40岁的个体的家族中，染色体17 q（MLOD = 2.28; LOD = 2.62），8p（MLOD = 2.01; LOD = 2.22）和5 q（MLOD = 2.39; LOD = 1.50）总体和迟发型PD家族，染色体9 q（MLOD = 1.52; LOD = 2.59）。结论我们的数据表明parkin基因在帕金森病的早期发病中起重要作用。原发性PD和多种遗传因素在特发性晚发性PD发病中可能起重要作用。
Context The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD.Objective To identify genetic risk factors for idiopathic PD.Design, Setting, and Participants Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n=344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status.Main Outcome Measures Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis.Results Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD, = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-non responsive patients.Conclusions Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.