通过ATAC-seq和ChIP实验发现,(GGGGCC)n的异常扩增导致C9orf72启动子区的染色体结构和表观遗传修饰异常。进一步研究证实,敲降DAXX,能过纠正(GGGGCC)n扩增突变导致的染色体异常,从而上调正常条件下和应激条件下的 C9orf72转录表达。更重要...
72基因GGGGCC重复序列动态突变的引物组,试剂盒及方法,引物组的正向引物C9R4的5'端有荧光基团标记,本发明方法通过提取DNA并利用引物组进行PCR扩增,对PCR扩增后的产物进行毛细管电泳,分析C9orf72基因GGGGCC重复序列情况,得出C9orf72基因GGGGCC重复数,通过C9orf72基因GGGGCC重复数实现对痴呆相关C9orf72基因进行评估,整个检测...
研究发现,CRISPR-Cas13d可以被优化以特异性地靶向C9orf72-ALS病人细胞中的GGGGCC重复RNA,并显著减少源自GGGGCC重复RNA的多聚二肽重复蛋白的翻译。 在这项研究中,研究人员首先构建了绿色荧光蛋白报告系统并比较了Cas13b和Cas13d靶向GGGGCC...
摘要: 目的 检测中国内地家族性肌萎缩侧索硬化(fALS)患者9号染色体开放阅读框72(C9ORF72)基因六核苷酸(GGGGCC)中度重复扩增(重复数为20 ～ 30)的发生率,分析其临床表型并探讨C9ORF72基因中度重复对中国内地fALS患者的意义.方法 对2007-2013年就诊于北京大学第三医院的62例fALS患者进行临床资料收集并提取DNA,检测C9...
We analyzed the GGGGCC repeat expansions of C9orf72 gene in patients with SCA3/MJD from mainland China to determine whether the C9orf72 gene plays a role in the pathogenesis of SCA3/MJD. In our study, there were no pathogenic repeats (>30 repeats) detected in either the patients or ...
Nucleotide Repeat Disease RNA Structure RNA-Protein Interaction ALS-FTD C9ORF72 G-quadruplex Multimolecular TranslationCited by (0)* This work was supported by grants from the Amyotrophic Lateral Sclerosis Association of America (to C. E. P.), the Canadian Institutes of Health Research (CIHR) to...
Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia. Acta Neuropathol. 2013; 126:401-409. [PubMed: 23818065]Fratta P, Poulter M, Lashley T, Rohrer JD, Polke JM, Beck J, Ryan N, Hensman D, Mizielinska S, Waite AJ, Lai MC, Gend- ron TF, Petrucelli L, ...
An expanded GGGGCC hexanucleotide of more than 30 repeats (termed (G4C2)30+) within C9orf72 is the most prominent mutation in familial frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) (termed C9+). Through an unbiased large-scale screen of (G4C2)49-expressing Drosop...
ALS/FTD患者的9号染色体开放阅读框72基因(C9ORF72)的非编码区存在大量的GGGGCC六核苷酸重复扩增,且GGGGCC六核苷酸重复扩增是ALS/FTD最常见的遗传病因。然而其具体的发病机制至今不明。已有研究发现GGGGCC六核苷酸重复扩增抑制下游基因转录,且GGGGCC六核苷酸重复扩增非编码RNA(r(GGGGCC)n)可导致神经退行性变。本研究的...
Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)·(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. These findings provide a ...