Identification of novel susceptibility loci for Guam neurodegenerative disease: challenges of genome scans in genetic isolates.
Identification of novel susceptibility loci for Guam neurodegenerative disease: challenges of genome scans in genetic isolates.
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关岛神经退行性疾病新易感位点的鉴定：遗传分离株基因组扫描的挑战。
DOI：
10.1093/hmg/ddp300
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发表时间：
2009
影响因子：
3.5
通讯作者：
Wijsman,EllenM
中科院分区：
文献类型：
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作者：
Sieh,Weiva;Choi,Yoonha;Chapman,NicolaH;Craig,Ulla-Katrina;Steinbart,EllenJ;Rothstein,JosephH;Oyanagi,Kiyomitsu;Garruto,RalphM;Bird,ThomasD;Galasko,DouglasR;Schellenberg,GerardD;Wijsman,EllenM
肌萎缩性侧索硬化症/帕金森氏症-痴呆症（ALS/PDC）是关岛查莫罗人和其他太平洋岛屿人口中发现的一种致命的神经退行性疾病。病因尚不清楚，尽管遗传和环境因素似乎都很重要。为了确定ALS/PDC的基因座，我们对迄今为止最大的样本进行了全基因组连锁和关联分析，使用了大约400个微卫星标记，包括几乎完整的所有活着的和以前采样的死亡病例样本。从关岛的一个村庄确定了一个单一的、庞大的、复杂的谱系，通过基于人口的神经学筛查和档案审查，从关岛其他地方确定了一个较小的家庭和一个病例对照样本。我们在12号染色体上发现了两个具有新的ALS/PDC位点的区域，并在17号染色体上发现了themapregion参与的支持证据。在我们最初的扫描中，12p上的D12S1617给出了最强的连锁证据（最大LOD评分，Zmax= 4.03），在完整的病例对照样本中，该标记和另一个附近标记的等位基因关联的证据得到了额外的支持。在侧面标记的支持下，12q上的D12S79也提供了显著的连锁证据（Zmax= 3.14）。我们的研究结果表明，ALS/PDC可能受到多达三个位点的影响，同时说明了孤立群体遗传分析中固有的挑战，以及在这种情况下有用的分析策略。阐明ALS/PDC的遗传基础有助于提高我们对阿尔茨海默病、帕金森病、额颞叶痴呆和ALS等相关神经退行性疾病的认识。
Amyotrophic lateral sclerosis/parkinsonism–dementia complex (ALS/PDC) is a fatal neurodegenerative disease found in the Chamorro people of Guam and other Pacific Island populations. The etiology is unknown, although both genetic and environmental factors appear important. To identify loci for ALS/PDC, we conducted both genome-wide linkage and association analyses, using approximately 400 microsatellite markers, in the largest sample assembled to date, comprising a nearly complete sample of all living and previously sampled deceased cases. A single, large, complex pedigree was ascertained from a village on Guam, with smaller families and a case–control sample ascertained from the rest of Guam by population-based neurological screening and archival review. We found significant evidence for two regions with novel ALS/PDC loci on chromosome 12 and supportive evidence for the involvement of theMAPTregion on chromosome 17. D12S1617 on 12p gave the strongest evidence of linkage (maximum LOD score,Zmax= 4.03) in our initial scan, with additional support in the complete case–control sample in the form of evidence of allelic association at this marker and another nearby marker. D12S79 on 12q also provided significant evidence of linkage (Zmax= 3.14) with support from flanking markers. Our results suggest that ALS/PDC may be influenced by as many as three loci, while illustrating challenges that are intrinsic in genetic analyses of isolated populations, as well as analytical strategies that are useful in this context. Elucidation of the genetic basis of ALS/PDC should improve our understanding of related neurodegenerative disorders including Alzheimer disease, Parkinson disease, frontotemporal dementia and ALS.
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影响因子：
3.3
作者：
J. K. Pritchard;Matthew Stephens;Peter Donnelly
通讯作者：
J. K. Pritchard;Matthew Stephens;Peter Donnelly
家族性乳腺癌与染色体 17q21 的连锁可能不仅限于早发性疾病。
影响因子：
9.8
作者：
Patricia Margaritte;Catherine Bonaïti;Mary Claire King;Françoise Clerget‐Darpoux
通讯作者：
Françoise Clerget‐Darpoux
15 – 关岛肌萎缩侧索硬化症/帕金森病-痴呆症
DOI：
10.1016/b978-012351830-9/50017-2
发表时间：
2001
期刊：
--
影响因子：
--
作者：
D. Perl
通讯作者：
D. Perl
用于计算遗传位置分数的随机游走方法。
影响因子：
9.8
作者：
Kenneth Lange;Eric M. Sobel
通讯作者：
Eric M. Sobel
影响因子：
1.9
作者：
CLERGETDARPOUX, F;BONAITIPELLIE, C;HOCHEZ, J
通讯作者：
HOCHEZ, J