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      Applying genetic technologies to combat infectious diseases in aquaculture

      review-article
      1 , 2 , , 3 , 1 , 3 , 1 , 2 , 3 , 2 , 4 , 1 , 1 , 2 , 2 , 3 , 5 , 1 , 3 , 1 , 1 , 1 , 1 , 3 , 6 , 7 , 7 , 8 , 8 , 9 , 10 , 11 , 11 , 12 , 13 , 4 , 1 , 14 , 1 , 7
      Reviews in Aquaculture
      John Wiley and Sons Inc.
      gene editing, genomic selection, host resistance, sea lice, transcriptomics, white‐spot syndrome virus

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          Abstract

          Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies—sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter‐ and intra‐species variation in pathogen/parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.

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          Integrated analysis of multimodal single-cell data

          Summary The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce “weighted-nearest neighbor” analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.
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            A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

            Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
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              Multiplex genome engineering using CRISPR/Cas systems.

              Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
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                Author and article information

                Contributors
                nick.robinson@nofima.no
                Journal
                Rev Aquac
                Rev Aquac
                10.1111/(ISSN)1753-5131
                RAQ
                Reviews in Aquaculture
                John Wiley and Sons Inc. (Hoboken )
                1753-5123
                1753-5131
                05 September 2022
                March 2023
                : 15
                : 2 ( doiID: 10.1111/raq.v15.2 )
                : 491-535
                Affiliations
                [ 1 ] Nofima AS Tromsø Norway
                [ 2 ] Sustainable Aquaculture Laboratory—Temperate and Tropical (SALTT) School of BioSciences, The University of Melbourne Melbourne Victoria Australia
                [ 3 ] The Roslin Institute and Royal (Dick) School of Veterinary Studies The University of Edinburgh Edinburgh UK
                [ 4 ] Institute of Marine Research, Matre Research Station Matredal Norway
                [ 5 ] Sydney School of Veterinary Science The University of Sydney Camden Australia
                [ 6 ] Atlantic Veterinary College The University of Prince Edward Island Charlottetown Prince Edward Island Canada
                [ 7 ] Benchmark Genetics Bergen Norway
                [ 8 ] Institute of Aquaculture University of Stirling Stirling Scotland UK
                [ 9 ] Blue Analytics, Kong Christian Frederiks Plass 3 Bergen Norway
                [ 10 ] Rothamsted Research Hertfordshire UK
                [ 11 ] Institute of Marine Research, Austevoll Research Station, Ecosystem Acoustics Group Tromsø Norway
                [ 12 ] Bigelow Laboratory for Ocean Sciences Boothbay Maine USA
                [ 13 ] Department of Marine Sciences University of Gothenburg Gothenburg Sweden
                [ 14 ] Cargill Aqua Nutrition Bergen Norway
                Author notes
                [*] [* ] Correspondence

                Nicholas A. Robinson, Hutchinson Avenue, Warrandyte, VIC 3113, Australia.

                Email: nick.robinson@ 123456nofima.no

                Author information
                https://orcid.org/0000-0003-1724-2551
                https://orcid.org/0000-0002-9616-5912
                https://orcid.org/0000-0003-3394-3462
                https://orcid.org/0000-0002-6702-5304
                https://orcid.org/0000-0002-6455-7372
                https://orcid.org/0000-0002-2820-0421
                https://orcid.org/0000-0001-5092-1105
                https://orcid.org/0000-0002-1217-7079
                https://orcid.org/0000-0001-8041-426X
                https://orcid.org/0000-0002-2658-6973
                https://orcid.org/0000-0002-6343-2295
                https://orcid.org/0000-0002-5737-3575
                https://orcid.org/0000-0002-5166-5497
                https://orcid.org/0000-0003-3544-0519
                https://orcid.org/0000-0002-7692-7756
                https://orcid.org/0000-0002-7885-2989
                https://orcid.org/0000-0003-1805-0762
                Article
                RAQ12733
                10.1111/raq.12733
                10946606
                38504717
                edae139a-282e-4398-aa8c-8cf88bdd8293
                © 2022 The Authors. Reviews in Aquaculture published by John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 July 2022
                : 15 March 2022
                : 16 August 2022
                Page count
                Figures: 3, Tables: 6, Pages: 45, Words: 46917
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council , doi 10.13039/501100000268;
                Award ID: BB/V009818/1
                Funded by: Fiskeri ‐ og havbruksnæringens forskningsfond
                Award ID: 901631
                Funded by: Norges Forskningsråd , doi 10.13039/501100005416;
                Award ID: 244131
                Award ID: 320619
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                March 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.9 mode:remove_FC converted:18.03.2024

                gene editing,genomic selection,host resistance,sea lice,transcriptomics,white‐spot syndrome virus

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