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https://www.readbyqxmd.com/read/28527116/genome-editing-in-drosophila-melanogaster-from-basic-genome-engineering-to-the-multipurpose-crispr-cas9-system
#1
REVIEW
Xingjie Ren, Kristof Holsteens, Haiyi Li, Jin Sun, Yifan Zhang, Lu-Ping Liu, Qingfei Liu, Jian-Quan Ni
Nowadays, genome editing tools are indispensable for studying gene function in order to increase our knowledge of biochemical processes and disease mechanisms. The extensive availability of mutagenesis and transgenesis tools make Drosophila melanogaster an excellent model organism for geneticists. Early mutagenesis tools relied on chemical or physical methods, ethyl methane sulfonate (EMS) and X-rays respectively, to randomly alter DNA at a nucleotide or chromosomal level. Since the discovery of transposable elements and the availability of the complete fly genome, specific genome editing tools, such as P-elements, zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have undergone rapid development...
May 1, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28523919/editing-plants-for-virus-resistance-using-crispr-cas
#2
J C Green, J S Hu
This minireview summarizes recent advancements using the clustered regularly interspaced palindromic repeats-associated nuclease systems (CRISPR-Cas) derived from prokaryotes to breed plants resistant to DNA and RNA viruses. The CRISPR-Cas system represents a powerful tool able to edit and insert novel traits into plants precisely at chosen loci offering enormous advantages to classical breeding. Approaches to engineering plant virus resistance in both transgenic and non-transgenic plants are discussed. Iterations of the CRISPR-Cas system, FnCas9 and C2c2 capable of editing RNA in eukaryotic cells offer a particular advantage for providing resistance to RNA viruses which represent the great majority of known plant viruses...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#3
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523546/histone-modifications-in-major-depressive-disorder-and-related-rodent-models
#4
Jan M Deussing, Mira Jakovcevski
Major depressive disorder (MDD) is a multifactorial disease, weakly linked to multiple genetic risk factors. In contrast to that, environmental factors and "gene × environment" interaction between specific risk genes and environmental factors, such as severe or early stress exposure, have been strongly linked to MDD vulnerability. Stressors can act on the interface between an organism and the environment, the epigenome. The molecular foundation for the impact of stressors on the risk to develop MDD is based on the hormonal stress response itself: the glucocorticoid receptor (GR, encoded by NR3C1)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#5
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28522325/generation-of-chromosomal-translocations-that-lead-to-conditional-fusion-protein-expression-using-crispr-cas9-and-homology-directed-repair
#6
Fabio Vanoli, Maria Jasin
Recurrent chromosomal translocations often lead to expression of fusion proteins associated with oncogenic transformation. To study translocations and downstream events, genome editing techniques have been developed to generate chromosomal translocations through non-homologous end joining of DNA double-strand breaks introduced at the two participating endogenous loci. However, the frequencies at which these events occur is usually too low to efficiently clone cells carrying the translocation. This article provides a detailed method using CRISPR-Cas9 technology and homology-directed repair to efficiently isolate cells harboring a chromosomal translocation...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28522157/antiviral-goes-viral-harnessing-crispr-cas9-to-combat-viruses-in-humans
#7
REVIEW
Jasper Adriaan Soppe, Robert Jan Lebbink
The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy...
May 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28512350/mechanisms-of-action-and-regulation-of-atp-dependent-chromatin-remodelling-complexes
#8
REVIEW
Cedric R Clapier, Janet Iwasa, Bradley R Cairns, Craig L Peterson
Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation...
May 17, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28509877/human-beta-defensin-2-selectively-inhibits-hiv-1-in-highly-permissive-ccr6%C3%A2-%C2%BAcd4%C3%A2-%C2%BA-t-cells
#9
Mark K Lafferty, Lingling Sun, Aaron Christensen-Quick, Wuyuan Lu, Alfredo Garzino-Demo
Chemokine receptor type 6 (CCR6)⁺CD4⁺ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4⁺ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6⁺CD4⁺ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28509669/genetic-advances-in-systemic-lupus-erythematosus-an-update
#10
Lingyan Chen, David L Morris, Timothy J Vyse
PURPOSE OF REVIEW: More than 80 susceptibility loci are now reported to show robust genetic association with systemic lupus erythematosus (SLE). The differential functional effects of the risk alleles for the majority of these loci remain to be defined. Here, we review current SLE association findings and the recent progress in the annotation of noncoding regions of the human genome as well as the new technologies and statistical methods that can be applied to further the understanding of SLE genetics...
May 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28508516/fell-muir-review-collagen-fibril-formation-in%C3%A2-vitro-and-in%C3%A2-vivo
#11
REVIEW
Karl E Kadler
It is a great honour to be awarded the Fell Muir Prize for 2016 by the British Society of Matrix Biology. As recipient of the prize, I am taking the opportunity to write a minireview on collagen fibrillogenesis, which has been the focus of my research for 33 years. This is the process by which triple helical collagen molecules assemble into centimetre-long fibrils in the extracellular matrix of animals. The fibrils appeared a billion years ago at the dawn of multicellular animal life as the primary scaffold for tissue morphogenesis...
May 16, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28508290/crispr-cas9-mediated-somatic-and-germline-gene-correction-to-restore-hemostasis-in-hemophilia-b-mice
#12
Cong Huai, Chenqiang Jia, Ruilin Sun, Peipei Xu, Taishan Min, Qihan Wang, Chengde Zheng, Hongyan Chen, Daru Lu
Hemophilia B (HB) is an X-linked disorder caused by defects of F9 encoded coagulation factor IX, which is an ideal model for gene therapy. Most existing HB gene therapies are based on viral mediated gene supplementation, which could increase immunoreaction. In this study, CRISPR/Cas9 system was used for gene correction in an F9 mutant HB mouse model in both adult mice (in vivo) and in germline cells (ex vivo). In vivo, naked Cas9-sgRNA plasmid and donor DNA were delivered to HB mice livers to recover the mutation via hydrodynamic tail vein (HTV) injection...
May 15, 2017: Human Genetics
https://www.readbyqxmd.com/read/28507698/formicamycins-antibacterial-polyketides-produced-by-streptomyces-formicae-isolated-from-african-tetraponera-plant-ants
#13
Zhiwei Qin, John T Munnoch, Rebecca Devine, Neil A Holmes, Ryan F Seipke, Karl A Wilkinson, Barrie Wilkinson, Matthew I Hutchings
We report a new Streptomyces species named S. formicae that was isolated from the African fungus-growing plant-ant Tetraponera penzigi and show that it produces novel pentacyclic polyketides that are active against MRSA and VRE. The chemical scaffold of these compounds, which we have called the formicamycins, is similar to the fasamycins identified from the heterologous expression of clones isolated from environmental DNA, but has significant differences that allow the scaffold to be decorated with up to four halogen atoms...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28506212/guideseq-a-bioconductor-package-to-analyze-guide-seq-datasets-for-crispr-cas-nucleases
#14
Lihua Julie Zhu, Michael Lawrence, Ankit Gupta, Hervé Pagès, Alper Kucukural, Manuel Garber, Scot A Wolfe
BACKGROUND: Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated the investigation of a broad range of biological questions. These nucleases also hold tremendous promise for treating a variety of genetic disorders. In the context of their therapeutic application, it is important to identify the spectrum of genomic sequences that are cleaved by a candidate nuclease when programmed with a particular guide RNA, as well as the cleavage efficiency of these sites...
May 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28505093/the-crucial-role-of-dna-methylation-and-mecp2-in-neuronal-function
#15
REVIEW
Maria Fasolino, Zhaolan Zhou
A neuron is unique in its ability to dynamically modify its transcriptional output in response to synaptic activity while maintaining a core gene expression program that preserves cellular identity throughout a lifetime that is longer than almost every other cell type in the body. A contributing factor to the immense adaptability of a neuron is its unique epigenetic landscape that elicits locus-specific alterations in chromatin architecture, which in turn influences gene expression. One such epigenetic modification that is sensitive to changes in synaptic activity, as well as essential for maintaining cellular identity, is DNA methylation...
May 13, 2017: Genes
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#16
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28499832/versatile-and-precise-gene-targeting-strategies-for-functional-studies-in-mammalian-cell-lines
#17
REVIEW
M Wassef, A Luscan, A Battistella, S Le Corre, H Li, M R Wallace, M Vidaud, R Margueron
The advent of programmable nucleases such as ZFNs, TALENs and CRISPR/Cas9 has brought the power of genetic manipulation to widely used model systems. In mammalian cells, nuclease-mediated DNA double strand break is mainly repaired through the error-prone non-homologous end-joining (NHEJ) repair pathway, eventually leading to accumulation of small deletions or insertions (indels) that can inactivate gene function. However, due to the variable size of the indels and the polyploid status of many cell lines (e...
May 10, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28499063/high-efficient-multi-sites-genome-editing-in-allotetraploid-cotton-gossypium-hirsutum-using-crispr-cas9-system
#18
Pengcheng Wang, Jun Zhang, Lin Sun, Yizan Ma, Jiao Xu, Sijia Liang, Jinwu Deng, Jiafu Tan, Qinghua Zhang, Lili Tu, Henry Daniell, Shuangxia Jin, Xianlong Zhang
Gossypium hirsutum is an allotetraploid with a complex genome. Most genes have multiple copies that belong to At and Dt subgenomes. Sequence similarity is also very high between gene homologs. To efficiently achieve site/gene-specific mutation is quite needed. Due to its high efficiency and robustness, the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has exerted broad site-specific genome editing from prokaryotes to eukaryotes. In this study, we utilized a CRISPR/Cas9 system to generate two sgRNAs in a single vector to conduct multiple sites genome editing in allotetraploid cotton...
May 12, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28497568/neuropsychological-phenotypes-of-76-individuals-with-joubert-syndrome-evaluated-at-a-single-center
#19
Angela C Summers, Joseph Snow, Edythe Wiggs, Alexander G Liu, Camilo Toro, Andrea Poretti, Wadih M Zein, Brian P Brooks, Melissa A Parisi, Sara Inati, Dan Doherty, Meghana Vemulapalli, Jim C Mullikin, Thierry Vilboux, William A Gahl, Meral Gunay-Aygun
Joubert syndrome (JS) is a genetically heterogeneous ciliopathy characterized by hypo-dysplasia of the cerebellar vermis, a distinct hindbrain/midbrain malformation (molar tooth sign), and intellectual disability. We evaluated the neuropsychological profiles of 76 participants with JS in the context of molecular genetics and clinical covariates. Evaluations included neuropsychological testing, structured parental interviews, DNA sequencing, brain magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic examination, and assessment for renal and hepatic disease...
May 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28497073/integrase-deficient-lentiviral-vector-as-an-all-in-one-platform-for-highly-efficient-crispr-cas9-mediated-gene-editing
#20
Pavel I Ortinski, Bernadette O'Donovan, Xiaoyu Dong, Boris Kantor
The CRISPR/Cas9 systems have revolutionized the field of genome editing by providing unprecedented control over gene sequences and gene expression in many species, including humans. Lentiviral vectors (LVs) are one of the primary delivery platforms for the CRISPR/Cas9 system due to their ability to accommodate large DNA payloads and sustain robust expression in a wide range of dividing and non-dividing cells. However, long-term expression of LV-delivered Cas9/guide RNA may lead to undesirable off-target effects characterized by non-specific RNA-DNA interactions and off-target DNA cleavages...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
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