Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy.
Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy.
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DOI：
10.1186/1756-6606-4-24
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发表时间：
2011-06-10
期刊：
影响因子：
3.6
通讯作者：
Matsubara K
中科院分区：
文献类型：
--
作者：
Sasaki H;Emi M;Iijima H;Ito N;Sato H;Yabe I;Kato T;Utsumi J;Matsubara K
多系统萎缩(MSA)是一种散发性疾病。其发病机制可能涉及多种遗传和非遗传因素，但其病因尚不清楚。我们假设MSA患者的基因组会在感兴趣的基因或基因组区域表现出拷贝数变异(CNV)。为了确定增加MSA风险的基因组改变，我们检查了一对与MSA表型不一致的同卵双胞胎和32名MSA患者。通过使用CNV珠芯片和基于比较基因组杂交(CGH)的CNV微阵列进行全基因组CNV分析，然后进行区域靶向、高密度、定制的寡核苷酸平铺微阵列分析，我们在患病的MZ双生子和31名MSA患者中的10名MSA患者中发现了19p13.3远端350-kb的转化蛋白2(SHC2)基因的疾病特异性拷贝数丢失(p=1.04×10-8，优势比=89.8，Pearson卡方检验)。SHC2的拷贝数丢失强烈表明与MSA之间存在因果联系。对表型不一致的MZ双胞胎进行CNV分析是识别疾病易感基因的有力工具。我们的结果将有助于确定新的诊断措施、治疗靶点和更好地了解MSA的病因。
Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-transforming protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10-8, odds ratio = 89.8, Pearson's chi-square test). Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
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影响因子：
11.2
作者：
Scholz, Sonja W.;Houlden, Henry;Schulte, Claudia;Sharma, Manu;Li, Abi;Berg, Daniela;Melchers, Anna;Paudel, Reema;Gibbs, J. Raphael;Simon-Sanchez, Javier;Paisan-Ruiz, Coro;Bras, Jose;Ding, Jinhui;Chen, Honglei;Traynor, Bryan J.;Arepalli, Sampath;Zonozi, Ryan R.;Revesz, Tamas;Holton, Janice;Wood, Nick;Lees, Andrew;Oertel, Wolfgang;Wuellner, Ullrich;Goldwurm, Stefano;Pellecchia, Maria Teresa;Illig, Thomas;Riess, Olaf;Fernandez, Hubert H.;Rodriguez, Ramon L.;Okun, Michael S.;Poewe, Werner;Wenning, Gregor K.;Hardy, John A.;Singleton, Andrew B.;Gasser, Thomas
通讯作者：
Gasser, Thomas
影响因子：
--
作者：
Hara, Kenju;Momose, Yoshio;Tsuji, Shoji
通讯作者：
Tsuji, Shoji
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.9
作者：
Morris, HR;Vaughan, JR;Wood, NW
通讯作者：
Wood, NW