Whole exome analysis for causative genes of familial IgA nephropathy

家族性IgA肾病致病基因的全外显子分析

• 批准号: 23591185
• 负责人: GOTO Shin
• 金额: $ 3.33万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591185/
• 关键词: 家族性IgA腎症; エクソーム解析; 連鎖解析; 全ゲノム連鎖解析; 次世代シークエンサー

In sporadic IgA nephropathy (IgAN), GWAS disclosed several risk variants, however, causative genes for familial IgAN remained elusive. We applied exome sequencing analysis in family comprising of four biopsy-proven IgAN. To identify the causative gene variant, several filtering screening were carried out based on non-synonymous, frequency less than one percent of 1000 genome project, and heterozygosity fitted with autosomal dominant inheritance. Finally, 13 variants were selected shared by all affected individuals. Among them, EEA1 variant were completely cosegregated with affection status of the family members, showed significant higher values in sequence conservation and prediction of functional changes of protein by amino-acid substitution. We are now investigating the functional analysis of EEA1 variant, and it is expected that these analyses will lead to the development of innovative therapeutics.

在散发性伊加肾病（IgAN）中，GWAS揭示了几种风险变体，然而，家族性IgAN的致病基因仍然难以捉摸。我们应用外显子组测序分析在家庭包括四个活检证实的IgA肾病。为了确定致病基因变异，根据非同义、频率低于1000个基因组计划的1%和符合常染色体显性遗传的杂合性进行了多次筛选。最后，选择了所有受影响个体共有的13个变体。其中，EEA1变异体与家族成员的患病状态完全共分离，在序列保守性和氨基酸替换预测蛋白质功能变化方面显示出显著较高的价值。我们现在正在研究EEA1变体的功能分析，预计这些分析将导致创新疗法的发展。

项目成果

Exome Sequencing Identifies a Novel EEA1 Variant in Japanese Familial IgA Nephropathy

外显子组测序鉴定出日本家族性 IgA 肾病的新型 EEA1 变异

• 发表时间: 2012
• 作者: Shin Goto;Kazuyoshi Hosomichi;Hiroyasu Tsukaguchi;Ichiei Narita
• 通讯作者: Ichiei Narita

Symposium : Membranoproliferative glomerulonephritis

研讨会：膜增生性肾小球肾炎

• 发表时间: 2011
• 作者: Shin Goto;Kazuyoshi Hosomichi;Hiroyasu Tsukaguchi;Ichiei Narita;Narita I
• 通讯作者: Narita I

Role of the p.E66Q variant of GLA in the progression of chronic kidney disease

GLA p.E66Q 变体在慢性肾病进展中的作用

• DOI: 10.1007/s10157-014-0969-y
• 发表时间: 2014
• 期刊: Clin Exp Nephrol
• 影响因子: 2.3
• 作者: Watanabe H;Goto S;Miyashita A;Maruyama H;Wakasugi M;Yokoseki A;Kuwano R;Narita I
• 通讯作者: Narita I

家族内集積を示す腎疾患のエクソーム解析

肾脏疾病的外显子组分析显示家族积累

• 作者: 後藤 眞;細道一善;塚口裕康;渡辺博文;井ノ上逸朗;成田一衛
• 通讯作者: 成田一衛

Genome-wide linkagescan of Japanese families with IgA nephropathy

日本 IgA 肾病家族的全基因组连锁扫描

• 发表时间: 2011
• 作者: Goto S;Tsukaguchi H;Wada M;Narita I
• 通讯作者: Narita I