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...
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...
MBNL1, a splicing factor that is sequestered in myotonic dystrophy patients by binding to expanded r(CUG)n repeat hairpins, does not bind the C9orf72 repeats, but the splicing factor ASF/SF2 can bind the r(GGGGCC)n repeat. Because multimolecular G-quadruplexes are enhanced by repeat length...
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...
RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing “c9RAN proteins.” Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. ...
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...
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。本研究的目的是进一步探讨GGGGCC六核苷酸重复扩增突变对神经元的损伤作用及其可能的机制。我们构建野生型质粒pEGFP-(GGGGCC)3(3个六核苷酸重复片段)和突变型质粒pEGFP-(GGGGCC)30 (30个六...
SCA3/MJD patients with intermediate/intermediate or short/intermediate genotype (short: <7 repeats; intermediate: 7-30 repeats) of the GGGGCC repeats had an earlier onset compared with those with short/short genotype. The presence of the intermediate allele of the GGGGCC repeats in the patients ...
肌萎缩侧索硬化是一种神经退行性疾病,由人类基因组中第9号染色体上某一位点的基因中GGGGCC(G4)重复序列的异常扩增导致基因表达水平下降而引起。下列相关分析正确的是( ) A. 人类基因组测序时需测定两条9号染色体中DNA的碱基序列 B. 基因中G4的异常扩增将导致染色体片段重复而发生染色体变异 C. 该病可能是G4...
The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA ...