Prediction of protein-destabilizing polymorphisms by manual curation with protein structure.
Prediction of protein-destabilizing polymorphisms by manual curation with protein structure.
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DOI：
10.1371/journal.pone.0050445
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gojobori T
中科院分区：
文献类型：
--
作者：
Gough CA;Homma K;Yamaguchi-Kabata Y;Shimada MK;Chakraborty R;Fujii Y;Iwama H;Minoshima S;Sakamoto S;Sato Y;Suzuki Y;Tada-Umezaki M;Nishikawa K;Imanishi T;Gojobori T
序列多态性与人类疾病之间的关系主要是在单核苷酸多态性（SNP）的影响方面进行研究，导致改变蛋白质结构和功能的单个氨基酸取代。然而，较少注意到更剧烈的序列多态性，其导致蛋白质序列的过早终止或序列中的大的变化、插入或缺失。我们已经分析了一个大的插入和缺失（indels）和单核苷酸多态性导致疾病相关基因的翻译提前终止的集合（n=512）。 通过使用基因组TO蛋白质（GTOP）数据库和一组特定标准的手动注释，以蛋白质结构中多态性位置的图形表示进行蛋白质不稳定效应的预测。预测44.4%的无义SNP、32.4%的移码indel和9.1%的非移码indel的蛋白质不稳定。对无义介导的衰变的预测允许推断哪些截短的蛋白质实际上会被翻译为缺陷蛋白质。这些病例包括与显性遗传疾病相关的蛋白质，表明这些疾病与毒性聚集之间的关系。我们的方法将是有用的，在确定潜在的聚集诱导多态性，可能有病理影响。
The relationship between sequence polymorphisms and human disease has been studied mostly in terms of effects of single nucleotide polymorphisms (SNPs) leading to single amino acid substitutions that change protein structure and function. However, less attention has been paid to more drastic sequence polymorphisms which cause premature termination of a protein’s sequence or large changes, insertions, or deletions in the sequence. We have analyzed a large set (n = 512) of insertions and deletions (indels) and single nucleotide polymorphisms causing premature termination of translation in disease-related genes. Prediction of protein-destabilization effects was performed by graphical presentation of the locations of polymorphisms in the protein structure, using the Genomes TO Protein (GTOP) database, and manual annotation with a set of specific criteria. Protein-destabilization was predicted for 44.4% of the nonsense SNPs, 32.4% of the frameshifting indels, and 9.1% of the non-frameshifting indels. A prediction of nonsense-mediated decay allowed to infer which truncated proteins would actually be translated as defective proteins. These cases included the proteins linked to diseases inherited dominantly, suggesting a relation between these diseases and toxic aggregation. Our approach would be useful in identifying potentially aggregation-inducing polymorphisms that may have pathological effects.
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影响因子：
14.9
作者：
Ramensky, V;Bork, P;Sunyaev, S
通讯作者：
Sunyaev, S
影响因子：
9.8
作者：
Imanishi T;Itoh T;Suzuki Y;O'Donovan C;Fukuchi S;Koyanagi KO;Barrero RA;Tamura T;Yamaguchi-Kabata Y;Tanino M;Yura K;Miyazaki S;Ikeo K;Homma K;Kasprzyk A;Nishikawa T;Hirakawa M;Thierry-Mieg J;Thierry-Mieg D;Ashurst J;Jia L;Nakao M;Thomas MA;Mulder N;Karavidopoulou Y;Jin L;Kim S;Yasuda T;Lenhard B;Eveno E;Suzuki Y;Yamasaki C;Takeda J;Gough C;Hilton P;Fujii Y;Sakai H;Tanaka S;Amid C;Bellgard M;Bonaldo Mde F;Bono H;Bromberg SK;Brookes AJ;Bruford E;Carninci P;Chelala C;Couillault C;de Souza SJ;Debily MA;Devignes MD;Dubchak I;Endo T;Estreicher A;Eyras E;Fukami-Kobayashi K;Gopinath GR;Graudens E;Hahn Y;Han M;Han ZG;Hanada K;Hanaoka H;Harada E;Hashimoto K;Hinz U;Hirai M;Hishiki T;Hopkinson I;Imbeaud S;Inoko H;Kanapin A;Kaneko Y;Kasukawa T;Kelso J;Kersey P;Kikuno R;Kimura K;Korn B;Kuryshev V;Makalowska I;Makino T;Mano S;Mariage-Samson R;Mashima J;Matsuda H;Mewes HW;Minoshima S;Nagai K;Nagasaki H;Nagata N;Nigam R;Ogasawara O;Ohara O;Ohtsubo M;Okada N;Okido T;Oota S;Ota M;Ota T;Otsuki T;Piatier-Tonneau D;Poustka A;Ren SX;Saitou N;Sakai K;Sakamoto S;Sakate R;Schupp I;Servant F;Sherry S;Shiba R;Shimizu N;Shimoyama M;Simpson AJ;Soares B;Steward C;Suwa M;Suzuki M;Takahashi A;Tamiya G;Tanaka H;Taylor T;Terwilliger JD;Unneberg P;Veeramachaneni V;Watanabe S;Wilming L;Yasuda N;Yoo HS;Stodolsky M;Makalowski W;Go M;Nakai K;Takagi T;Kanehisa M;Sakaki Y;Quackenbush J;Okazaki Y;Hayashizaki Y;Hide W;Chakraborty R;Nishikawa K;Sugawara H;Tateno Y;Chen Z;Oishi M;Tonellato P;Apweiler R;Okubo K;Wagner L;Wiemann S;Strausberg RL;Isogai T;Auffray C;Nomura N;Gojobori T;Sugano S
通讯作者：
Sugano S
影响因子：
7.7
作者：
Hojlund, K;Hansen, T;Beck-Nielsen, H
通讯作者：
Beck-Nielsen, H
影响因子：
14.9
作者：
Bairoch, A;Apweiler, R
通讯作者：
Apweiler, R
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE