Talk:Molecular Development - Genetics
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Cite this page: Hill, M.A. (2019, September 22) Embryology Molecular Development - Genetics. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Molecular_Development_-_Genetics
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<pubmed limit=5>Molecular Genetic Development</pubmed>
<pubmed limit=5>Genetic Development</pubmed>
CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein
Mol Genet Genomics. 2017 Jun;292(3):525-533. doi: 10.1007/s00438-017-1299-z. Epub 2017 Mar 1.
Tang L1,2, Zeng Y3, Du H3, Gong M4, Peng J4, Zhang B4, Lei M3, Zhao F5, Wang W6, Li X7, Liu J8.
Abstract Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research. KEYWORDS: CRISPR/Cas9; Cas9 protein; Gene modification; Homology-directed repair (HDR); Human zygotes PMID 28251317 DOI: 10.1007/s00438-017-1299-z
CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
Protein Cell. 2015 May;6(5):363-372. doi: 10.1007/s13238-015-0153-5. Epub 2015 Apr 18.
Liang P#1, Xu Y#1, Zhang X#1, Ding C#1, Huang R1, Zhang Z1, Lv J1, Xie X1, Chen Y1, Li Y1, Sun Y1, Bai Y1, Songyang Z1, Ma W1, Zhou C1, Huang J1. Author information Abstract Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing. Comment in Gene Editing and Germ-line Intervention: The Need for Novel Responses to Novel Technologies. [Mol Ther. 2015] The Genie Is Out of the Bottle. [IEEE Pulse. 2015] UK bioethicists eye designer babies and CRISPR cows. [Nature. 2016] PMID: 25894090 PMCID: PMC4417674 DOI: 10.1007/s13238-015-0153-5
A CRISPR view of development
Genes Dev. 2014 Sep 1;28(17):1859-72. doi: 10.1101/gad.248252.114.
Harrison MM1, Jenkins BV2, O'Connor-Giles KM3, Wildonger J4.
The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is poised to transform developmental biology by providing a simple, efficient method to precisely manipulate the genome of virtually any developing organism. This RNA-guided nuclease (RGN)-based approach already has been effectively used to induce targeted mutations in multiple genes simultaneously, create conditional alleles, and generate endogenously tagged proteins. Illustrating the adaptability of RGNs, the genomes of >20 different plant and animal species as well as multiple cell lines and primary cells have been successfully modified. Here we review the current and potential uses of RGNs to investigate genome function during development. © 2014 Harrison et al.; Published by Cold Spring Harbor Laboratory Press. KEYWORDS: CRISPR; Cas9; RNA-guided nuclease; development; genome editing; genome engineering PMID 25184674
The Genomic HyperBrowser: an analysis web server for genome-scale data
Nucleic Acids Res. 2013 Apr 30. [Epub ahead of print]
Sandve GK, Gundersen S, Johansen M, Glad IK, Gunathasan K, Holden L, Holden M, Liestøl K, Nygård S, Nygaard V, Paulsen J, Rydbeck H, Trengereid K, Clancy T, Drabløs F, Ferkingstad E, Kalas M, Lien T, Rye MB, Frigessi A, Hovig E. Source Department of Informatics, University of Oslo, PO Box 1080, Blindern, 0316 Oslo, Norway, Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, PO Box 4950, Nydalen, 0424 Oslo, Norway, Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, PO Box 4950, Nydalen, N-0424 Oslo, Norway, Department of Mathematics, University of Oslo, PO Box 1053, Blindern, 0316 Oslo, Norway, Department of Medical Biology, Faculty of Health Science, University of Tromsø, 9037 Tromsø, Norway, Statistics For Innovation, Norwegian Computing Center, 0314 Oslo, Norway, Bioinformatics Core Facility, Oslo University Hospital and University of Oslo, PO Box 4950 Nydalen, N-0424 Oslo, Norway, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway, Department of Informatics, University of Bergen, PO Box 7803, 5020 Bergen, Norway, Computational Biology Unit, Uni Computing, Uni Research AS, 5020 Bergen, Norway and Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, PO Box 1122 Blindern, 0317 Oslo, Norway. Abstract The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, researchers are faced with the challenge of how to best analyze and interpret their genome-scale datasets. A powerful way of representing genome-scale data is as feature-specific coordinates relative to reference genome assemblies, i.e. as genomic tracks. The Genomic HyperBrowser (http://hyperbrowser.uio.no) is an open-ended web server for the analysis of genomic track data. Through the provision of several highly customizable components for processing and statistical analysis of genomic tracks, the HyperBrowser opens for a range of genomic investigations, related to, e.g., gene regulation, disease association or epigenetic modifications of the genome. PMID 23632163
Galaxy is an open, web-based platform for data intensive biomedical research. Whether on this free public server or your own instance, you can perform, reproduce, and share complete analyses.
http://www.addgene.org/ Plasmid Repository
Genetics for Surgeons
Remedica Genetics Series
Patrick J Morrison, MD, FRCPCH, FFPHMI and Roy AJ Spence, OBE, MA, MD, FRCS.
University of Ulster, Queen's University Belfast and Belfast City Hospital Trust London: Remedica; 2005. ISBN-10: 1-901-34669-2 Copyright © 2005, Remedica.
This text is written in non technical language in three main sections: a general overview of the principles in genetics, a section on common genetic disorders that surgeons will encounter, a third section on familial cancers, which, in the case of breast, bowel, and ovarian cancers, account for around 10% of the cancers that surgeons encounter. A fourth section deals with the topics that surgeons and anesthetists should both know, while the glossary at the end of the book allows a quick reference to increasingly common genetics terms.