Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
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DOI：
10.1016/j.cell.2011.05.025
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发表时间：
2011-06-24
期刊：
影响因子：
64.5
通讯作者：
Noebels J
中科院分区：
文献类型：
--
作者：
Klassen T;Davis C;Goldman A;Burgess D;Chen T;Wheeler D;McPherson J;Bourquin T;Lewis L;Villasana D;Morgan M;Muzny D;Gibbs R;Noebels J
离子通道突变是影响大脑、心脏和其他组织的罕见孟德尔疾病的重要原因。我们在一个特征良好的人类样本中对237个通道基因进行了平行外显子组测序，比较了未受影响的个体和那些最常见的神经元兴奋性障碍-散发性特发性癫痫患者的不同特征。已知的孟德尔病基因中罕见的错义变异在两组中以相似的复杂性普遍存在，这表明即使是有害的离子通道突变也会给个体带来不确定的风险，这取决于与它们结合的其他变体。我们的发现表明，通过大规模测序努力发现变异只是阐明个人疾病风险背后复杂的等位基因体系的第一步。我们认为，在现实的细胞和网络模型的通道变化的电子模拟中，将是未来评估突变谱、致病性和药物反应的策略的关键，这些个体具有广泛的兴奋性障碍。
Ion channel mutations are an important cause of rare Mendelian disorders affecting brain, heart, and other tissues. We performed parallel exome sequencing of 237 channel genes in a well characterized human sample, comparing variant profiles of unaffected individuals to those with the most common neuronal excitability disorder, sporadic idiopathic epilepsy. Rare missense variation in known Mendelian disease genes is prevalent in both groups at similar complexity, revealing that even deleterious ion channel mutations confer uncertain risk to an individual depending on the other variants with which they are combined. Our findings indicate that variant discovery via large scale sequencing efforts is only a first step in illuminating the complex allelic architecture underlying personal disease risk. We propose that in silico modeling of channel variation in realistic cell and network models will be crucial to future strategies assessing mutation profile pathogenicity and drug response in individuals with a broad spectrum of excitability disorders.
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影响因子：
14.9
作者：
Dougherty JD;Schmidt EF;Nakajima M;Heintz N
通讯作者：
Heintz N
影响因子：
14.9
作者：
Harmar AJ;Hills RA;Rosser EM;Jones M;Buneman OP;Dunbar DR;Greenhill SD;Hale VA;Sharman JL;Bonner TI;Catterall WA;Davenport AP;Delagrange P;Dollery CT;Foord SM;Gutman GA;Laudet V;Neubig RR;Ohlstein EH;Olsen RW;Peters J;Pin JP;Ruffolo RR;Searls DB;Wright MW;Spedding M
通讯作者：
Spedding M
DOI：
10.1007/978-1-59745-520-6_7
发表时间：
2007-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bower, James M;Beeman, David
通讯作者：
Beeman, David
影响因子：
9.8
作者：
Bloodgood BL;Giessel AJ;Sabatini BL
通讯作者：
Sabatini BL
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.