Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9
نویسندگان
چکیده
منابع مشابه
Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9.
Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs endothelial corneal dystrophy, and C9orf72-ALS/FTD. Reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that deactivated Cas9 enzyme impedes transcription across expanded microsatellites. W...
متن کاملCell-free cloning of highly expanded CTG repeats by amplification of dimerized expanded repeats
We describe conditions for producing uninterrupted expanded CTG repeats consisting of up to 2000 repeats using 29 DNA polymerase. Previously, generation of such repeats was hindered by CTG repeat instability in plasmid vectors maintained in Escherichia coli and poor in vitro ligation of CTG repeat concatemers due to strand slippage. Instead, we used a combination of in vitro ligation and 29 DNA...
متن کاملA recurrent 14q32.2 microdeletion mediated by expanded TGG repeats.
Nearly all recurrent microdeletion/duplication syndromes described to date are characterized by the presence of flanking low copy repeats that act as substrates for non-allelic homologous recombination (NAHR) leading to the loss, gain or disruption of dosage sensitive genes. We describe an identical 1.11 Mb heterozygous deletion of 14q32.2 including the DLK1/GTL2 imprinted gene cluster in two u...
متن کاملBidirectional transcription stimulates expansion and contraction of expanded (CTG)*(CAG) repeats.
More than 12 neurogenetic disorders are caused by unstable expansions of (CTG)•(CAG) repeats. The expanded repeats are unstable in germline and somatic cells, with potential consequences for disease severity. Previous studies have shown that contractions of (CAG)(95) are more frequent when the repeat tract is transcribed. Here we determined whether transcription can promote repeat expansion, us...
متن کاملContracting CAG/CTG repeats using the CRISPR-Cas9 nickase
CAG/CTG repeat expansions cause over 13 neurological diseases that remain without a cure. Because longer tracts cause more severe phenotypes, contracting them may provide a therapeutic avenue. No currently known agent can specifically generate contractions. Using a GFP-based chromosomal reporter that monitors expansions and contractions in the same cell population, here we find that inducing do...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Molecular Cell
سال: 2017
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2017.09.033