Genome-wide genetic screening in the mammalian CNS

Genes linked to major neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, were first identified over 15 years ago, but neither a full molecular explanation for the cell loss seen in human patients nor a curative therapy has yet been achieved for any of these di...

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Main Authors: Wertz, Mary H., Heiman, Myriam
Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Format: Book chapter
Language:English
Published: Springer International Publishing 2020
Online Access:https://hdl.handle.net/1721.1/124812
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author Wertz, Mary H.
Heiman, Myriam
author2 Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
author_facet Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Wertz, Mary H.
Heiman, Myriam
author_sort Wertz, Mary H.
collection MIT
description Genes linked to major neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, were first identified over 15 years ago, but neither a full molecular explanation for the cell loss seen in human patients nor a curative therapy has yet been achieved for any of these diseases. In most model organisms, when new hypotheses are needed to explain a cellular process, genetic screens are the tool of choice. For example, ‘synthetic lethal’ screens can lead to the identification of genes that enhance the toxicity of a particular mutation, revealing pathways critical for surviving the mutation’s effects. To date, however, genome-wide unbiased screens are not feasible in mammalian central nervous system neurons except in vitro, which fails to capture the relevant disease pathologies, and no genome-wide screens have yet been conducted in the mammalian central nervous system. We outline in this short monograph the steps needed to implement a methodology that allows for genome-wide genetic screening in the central nervous system of mice to study both normal and degenerative disease gene function. ©2017
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spelling mit-1721.1/1248122022-09-30T21:08:24Z Genome-wide genetic screening in the mammalian CNS Wertz, Mary H. Heiman, Myriam Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Genes linked to major neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, were first identified over 15 years ago, but neither a full molecular explanation for the cell loss seen in human patients nor a curative therapy has yet been achieved for any of these diseases. In most model organisms, when new hypotheses are needed to explain a cellular process, genetic screens are the tool of choice. For example, ‘synthetic lethal’ screens can lead to the identification of genes that enhance the toxicity of a particular mutation, revealing pathways critical for surviving the mutation’s effects. To date, however, genome-wide unbiased screens are not feasible in mammalian central nervous system neurons except in vitro, which fails to capture the relevant disease pathologies, and no genome-wide screens have yet been conducted in the mammalian central nervous system. We outline in this short monograph the steps needed to implement a methodology that allows for genome-wide genetic screening in the central nervous system of mice to study both normal and degenerative disease gene function. ©2017 2020-04-22T18:34:13Z 2020-04-22T18:34:13Z 2017 2019-10-02T15:53:40Z Book chapter http://purl.org/eprint/type/JournalArticle 978-3-319-60191-5 978-3-319-60192-2 0945-6082 2196-3096 https://hdl.handle.net/1721.1/124812 Wertz, Mary H., and Heiman, Myriam, "Genome-wide genetic screening in the mammalian CNS." In Jaenisch, Rudolf, Feng Zhang, and Fred Gage, eds., Genome editing in neurosciences (Cham: Springer, 2017): p. 31-39 doi 10.1007/978-3-319-60192-2_3 ©2017 Author(s) en 10.1007/978-3-319-60192-2_3 Genome editing in neurosciences Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer International Publishing Springer
spellingShingle Wertz, Mary H.
Heiman, Myriam
Genome-wide genetic screening in the mammalian CNS
title Genome-wide genetic screening in the mammalian CNS
title_full Genome-wide genetic screening in the mammalian CNS
title_fullStr Genome-wide genetic screening in the mammalian CNS
title_full_unstemmed Genome-wide genetic screening in the mammalian CNS
title_short Genome-wide genetic screening in the mammalian CNS
title_sort genome wide genetic screening in the mammalian cns
url https://hdl.handle.net/1721.1/124812
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