20 results match your criteria indel restore

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Development of a CRISPR-Cas9 Based Luciferase Turn-On System as Nonhomologous End Joining Pathway Reporter.

Chembiochem 2021 Jun 7;22(12):2177-2181. Epub 2021 May 7.

Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China.

There is a need of a non-homologous end joining (NHEJ) pathway reporter system that facilitates screening and discovery of NHEJ chemical inhibitors. In this study, we developed a CRISPR-Cas9 based luciferase turn-on system as a NHEJ pathway reporter. By substituting nucleotide 205C with ATC, we introduced a reading-frame shift and a pre-stop codon into the luciferase coding region and thereby generated a bioluminescent signal mute HEK293T reporter cell line. Read More

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Physical mapping and InDel marker development for the restorer gene Rf in cytoplasmic male sterile CMS-D8 cotton.

BMC Genomics 2021 Jan 6;22(1):24. Epub 2021 Jan 6.

State Key Laboratory of Cotton Biology, Institute of Cotton Research of Chinese Academy of Agricultural Sciences, 38 Huanghe Dadao, Anyang, 455000, Henan, China.

Background: Cytoplasmic male sterile (CMS) with cytoplasm from Gossypium Trilobum (D8) fails to produce functional pollen. It is useful for commercial hybrid cotton seed production. The restore line of CMS-D8 containing Rf gene can restore the fertility of the corresponding sterile line. Read More

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January 2021

Sensitive and reliable evaluation of single-cut sgRNAs to restore dystrophin by a GFP-reporter assay.

PLoS One 2020 24;15(9):e0239468. Epub 2020 Sep 24.

Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America.

Most Duchenne muscular dystrophy (DMD) cases are caused by deletions or duplications of one or more exons that disrupt the reading frame of DMD mRNA. Restoring the reading frame allows the production of partially functional dystrophin proteins, and result in less severe symptoms. Antisense oligonucleotide mediated exon skipping has been approved for DMD, but this strategy needs repeated treatment. Read More

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November 2020

Acquired multiple secondary mutations upon PARPi resistance in a metastatic pancreatic cancer patient harboring a germline mutation.

Am J Transl Res 2020 15;12(2):612-617. Epub 2020 Feb 15.

The First Medical Center of Chinese PLA General Hospital Beijing, China.

PARP inhibitor (PARPi) therapies have been approved for treating multiple germline mutated (gm) advanced cancers including metastatic pancreatic cancer. Although significantly prolonged progression-free survival was observed in gm pancreatic cancer patients, there was no improved overall survival. The underlined resistant mechanism to PARPi therapy is worth pursuing. Read More

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February 2020

Superfine bacterial nanocellulose produced by reverse mutations in the bcsC gene during adaptive breeding of Komagataeibacter oboediens.

Carbohydr Polym 2019 Dec 5;226:115243. Epub 2019 Sep 5.

Interdisciplinary Graduate Program in Genetic Engineering, The Graduate School, Kasetsart University, Bangkok 10900, Thailand; Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand. Electronic address:

Nonsense mutation in the bcsC gene occurred in the ethanol-adapted strain of Komagataeibacter oboediens MSKU 3, E3 strain, resulting in the loss of the function to produce BNC. In this study, we tried to restore the BNC-producing ability of E3 strain by the following adaptive mutation through repetitive static culture, and obtained four BNC-producing revertant strains, of which the bcsC gene had InDel mutations near the frameshift mutation region in E3 strain, resulting in several amino acid alterations compared with the BcsC of MSKU 3. Each revertant produced BNCs with different productivity on the static culture. Read More

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December 2019

NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia.

Cell Stem Cell 2019 11 19;25(5):607-621.e7. Epub 2019 Sep 19.

Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Madrid 28040, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Madrid 28040, Spain; Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD/UAM), Madrid 28040, Spain. Electronic address:

Non-homologous end-joining (NHEJ) is the preferred mechanism used by hematopoietic stem cells (HSCs) to repair double-stranded DNA breaks and is particularly increased in cells deficient in the Fanconi anemia (FA) pathway. Here, we show feasible correction of compromised functional phenotypes in hematopoietic cells from multiple FA complementation groups, including FA-A, FA-C, FA-D1, and FA-D2. NHEJ-mediated repair of targeted CRISPR-Cas9-induced DNA breaks generated compensatory insertions and deletions that restore the coding frame of the mutated gene. Read More

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November 2019

A Carbonic Anhydrase Pseudogene Sensitizes Select Lineages to Low CO Tension.

J Bacteriol 2019 11 21;201(22). Epub 2019 Oct 21.

Committee on Microbiology, University of Chicago, Chicago, Illinois, USA

spp. are intracellular pathogens that cause a disease known as brucellosis. Though the genus is highly monomorphic at the genetic level, species have animal host preferences and some defining physiologic characteristics. Read More

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November 2019

Functional analysis of Fanconi anemia mutations in China.

Exp Hematol 2018 10 19;66:32-41.e8. Epub 2018 Jul 19.

Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Fanconi anemia (FA) is a rare recessive disease characterized by progressive bone marrow failure, congenital abnormalities, and increased incidence of cancers. To date, mutations in 22 genes can cause FA or an FA-like phenotype. In China, in addition to clinical information, FA diagnosis primarily relies on genetic sequencing because the chromosome breakage test is rarely performed. Read More

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October 2018

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

J Clin Immunol 2018 05 9;38(4):484-493. Epub 2018 May 9.

Department of Pediatric Immunology, Hacettepe University Medical School, İhsan Doğramacı Children's Hospital, Ankara, Turkey.

Introduction: Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. Read More

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Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug resistance mutations.

Nucleic Acids Res 2015 Mar 12;43(6):3256-71. Epub 2015 Mar 12.

Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia Department of Infectious Diseases, Monash University, Melbourne, Victoria 3004, Australia Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia

Resistance to combined antiretroviral therapy (cART) in HIV-1-infected individuals is typically due to nonsynonymous mutations that change the protein sequence; however, the selection of synonymous or 'silent' mutations in the HIV-1 genome with cART has been reported. These silent K65K and K66K mutations in the HIV-1 reverse transcriptase (RT) occur in over 35% of drug-experienced individuals and are highly associated with the thymidine analog mutations D67N and K70R, which confer decreased susceptibility to most nucleoside and nucleotide RT inhibitors. However, the basis for selection of these silent mutations under selective drug pressure is unknown. Read More

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Thiol peroxidase deficiency leads to increased mutational load and decreased fitness in Saccharomyces cerevisiae.

Genetics 2014 Nov 29;198(3):905-17. Epub 2014 Aug 29.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

Thiol peroxidases are critical enzymes in the redox control of cellular processes that function by reducing low levels of hydroperoxides and regulating redox signaling. These proteins were also shown to regulate genome stability, but how their dysfunction affects the actual mutations in the genome is not known. Saccharomyces cerevisiae has eight thiol peroxidases of glutathione peroxidase and peroxiredoxin families, and the mutant lacking all these genes (∆8) is viable. Read More

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November 2014

Gene correction of a duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in.

Hum Gene Ther 2013 Jul;24(7):692-701

School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, United Kingdom.

Duchenne muscular dystrophy (DMD) is a severe inherited, muscle-wasting disorder caused by mutations in the DMD gene. Gene therapy development for DMD has concentrated on vector-based DMD minigene transfer, cell-based gene therapy using genetically modified adult muscle stem cells or healthy wild-type donor cells, and antisense oligonucleotide-induced exon-skipping therapy to restore the reading frame of the mutated DMD gene. This study is an investigation into DMD gene targeting-mediated correction of deletions in human patient myoblasts using a target-specific meganuclease (MN) and a homologous recombination repair matrix. Read More

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Sequence context of indel mutations and their effect on protein evolution in a bacterial endosymbiont.

Genome Biol Evol 2013 ;5(3):599-605

Institute for Genome Sciences and Policy, Duke University, NC, USA.

Indel mutations play key roles in genome and protein evolution, yet we lack a comprehensive understanding of how indels impact evolutionary processes. Genome-wide analyses enabled by next-generation sequencing can clarify the context and effect of indels, thereby integrating a more detailed consideration of indels with our knowledge of nucleotide substitutions. To this end, we sequenced Blochmannia chromaiodes, an obligate bacterial endosymbiont of carpenter ants, and compared it with the close relative, B. Read More

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Functional analysis of in-frame indel ARID1A mutations reveals new regulatory mechanisms of its tumor suppressor functions.

Neoplasia 2012 Oct;14(10):986-93

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

AT-rich interactive domain 1A (ARID1A) has emerged as a new tumor suppressor in which frequent somatic mutations have been identified in several types of human cancers. Although most ARID1A somatic mutations are frame-shift or nonsense mutations that contribute to mRNA decay and loss of protein expression, 5% of ARID1A mutations are in-frame insertions or deletions (indels) that involve only a small stretch of peptides. Naturally occurring in-frame indel mutations provide unique and useful models to explore the biology and regulatory role of ARID1A. Read More

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October 2012

Predicting the effects of frameshifting indels.

Genome Biol 2012 Feb 9;13(2):R9. Epub 2012 Feb 9.

Department of Mathematics and Computer Science, Franklin and Marshall College, 415 Harrisburg Ave, Lancaster, PA 17603, USA.

Each human has approximately 50 to 280 frameshifting indels, yet their implications are unknown. We created SIFT Indel, a prediction method for frameshifting indels that has 84% accuracy. The percentage of human frameshifting indels predicted to be gene-damaging is negatively correlated with allele frequency. Read More

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February 2012

Endonucleases: tools to correct the dystrophin gene.

J Gene Med 2011 Oct;13(10):522-37

Unité de Recherche de Recherche en Génétique Humaine, Centre de Recherche de CHUL, CHUQ, Faculté de Médecine, Université Laval, Québec, Canada.

Background: Various endonucleases can be engineered to induce double-strand breaks (DSBs) in chosen DNA sequences. These DSBs are spontaneously repaired by nonhomologous-end-joining, resulting in micro-insertions or micro-deletions (INDELs). We detected, characterized and quantified the frequency of INDELs produced by one meganuclease (MGN) targeting the RAG1 gene, six MGNs targeting three introns of the human dystrophin gene and one pair of zinc finger nucleases (ZFNs) targeting exon 50 of the human dystrophin gene. Read More

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October 2011

Multiple reference genomes and transcriptomes for Arabidopsis thaliana.

Nature 2011 Aug 28;477(7365):419-23. Epub 2011 Aug 28.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

Genetic differences between Arabidopsis thaliana accessions underlie the plant's extensive phenotypic variation, and until now these have been interpreted largely in the context of the annotated reference accession Col-0. Here we report the sequencing, assembly and annotation of the genomes of 18 natural A. thaliana accessions, and their transcriptomes. Read More

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Precise excision of IS5 from the intergenic region between the fucPIK and the fucAO operons and mutational control of fucPIK operon expression in Escherichia coli.

J Bacteriol 2010 Apr 22;192(7):2013-9. Epub 2010 Jan 22.

Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA.

Excision of transposable genetic elements from host DNA occurs at low frequencies and is usually imprecise. A common insertion sequence element in Escherichia coli, IS5, has been shown to provide various benefits to its host by inserting into specific sites. Precise excision of this element had not previously been demonstrated. Read More

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Creation of a chloroplast microsatellite reporter for detection of replication slippage in Chlamydomonas reinhardtii.

Eukaryot Cell 2008 Apr 8;7(4):639-46. Epub 2008 Feb 8.

Department of Plant Biology, Michigan State University, East Lansing, MI 48824-1312, USA.

Microsatellites are composed of short tandem direct repeats; deletions or duplications of those repeats through the process of replication slippage result in microsatellite instability relative to other genomic loci. Variation in repeat number occurs so frequently that microsatellites can be used for genotyping and forensic analysis. However, an accurate assessment of the rates of change can be difficult because the presence of many repeats makes it difficult to determine whether changes have occurred through single or multiple events. Read More

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An iterative algorithm for correcting sequencing errors in DNA coding regions.

J Comput Biol 1996 ;3(3):333-44

Computer Science and Mathematics Division, Oak Ridge National Laboratory, Tennessee 37831-6364, USA.

Insertion and deletion (indel) sequencing errors in DNA coding regions disrupt DNA-to-protein translation frames, and hence make most frame-sensitive coding recognition approaches fail. This paper extends the authors' previous work on indel detection and "correction" algorithms, and presents a more effective algorithm for localizing indels that appear in DNA coding regions and "correcting" the located indels by inserting or deleting DNA bases. The algorithm localizes indels by discovering changes of the preferred translation frames within presumed coding regions, and then "corrects" them to restore a consistent translation frame within each coding region. Read More

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February 1997
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