Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types

Abstract Effective treatments targeting disease etiology are urgently needed for Alzheimer’s disease (AD). Although candidate AD genes have been identified and altering their levels may serve as therapeutic strategies, the consequence of such alterations remain largely unknown. Herein, we analyzed C...

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Autores principales:	Suraj K. Jaladanki, Abdulkadir Elmas, Gabriel Santos Malave, Kuan-lin Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/115836deb7f1469a99809dc9b0f95de5
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spelling	oai:doaj.org-article:115836deb7f1469a99809dc9b0f95de52021-12-02T17:34:30ZGenetic dependency of Alzheimer’s disease-associated genes across cells and tissue types10.1038/s41598-021-91713-22045-2322https://doaj.org/article/115836deb7f1469a99809dc9b0f95de52021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91713-2https://doaj.org/toc/2045-2322Abstract Effective treatments targeting disease etiology are urgently needed for Alzheimer’s disease (AD). Although candidate AD genes have been identified and altering their levels may serve as therapeutic strategies, the consequence of such alterations remain largely unknown. Herein, we analyzed CRISPR knockout/RNAi knockdown screen data for over 700 cell lines and evaluated cellular dependencies of 104 AD-associated genes previously identified by genome-wide association studies (GWAS) and gene expression network studies. Multiple genes showed widespread cell dependencies across tissue lineages, suggesting their inhibition may yield off-target effects. Meanwhile, several genes including SPI1, MEF2C, GAB2, ABCC11, ATCG1 were identified as genes of interest since their genetic knockouts specifically affected high-expressing cells whose tissue lineages are relevant to cell types found in AD. Overall, analyses of genetic screen data identified AD-associated genes whose knockout or knockdown selectively affected cell lines of relevant tissue lineages, prioritizing targets for potential AD treatments.Suraj K. JaladankiAbdulkadir ElmasGabriel Santos MalaveKuan-lin HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suraj K. Jaladanki Abdulkadir Elmas Gabriel Santos Malave Kuan-lin Huang Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
description	Abstract Effective treatments targeting disease etiology are urgently needed for Alzheimer’s disease (AD). Although candidate AD genes have been identified and altering their levels may serve as therapeutic strategies, the consequence of such alterations remain largely unknown. Herein, we analyzed CRISPR knockout/RNAi knockdown screen data for over 700 cell lines and evaluated cellular dependencies of 104 AD-associated genes previously identified by genome-wide association studies (GWAS) and gene expression network studies. Multiple genes showed widespread cell dependencies across tissue lineages, suggesting their inhibition may yield off-target effects. Meanwhile, several genes including SPI1, MEF2C, GAB2, ABCC11, ATCG1 were identified as genes of interest since their genetic knockouts specifically affected high-expressing cells whose tissue lineages are relevant to cell types found in AD. Overall, analyses of genetic screen data identified AD-associated genes whose knockout or knockdown selectively affected cell lines of relevant tissue lineages, prioritizing targets for potential AD treatments.
format	article
author	Suraj K. Jaladanki Abdulkadir Elmas Gabriel Santos Malave Kuan-lin Huang
author_facet	Suraj K. Jaladanki Abdulkadir Elmas Gabriel Santos Malave Kuan-lin Huang
author_sort	Suraj K. Jaladanki
title	Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
title_short	Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
title_full	Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
title_fullStr	Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
title_full_unstemmed	Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
title_sort	genetic dependency of alzheimer’s disease-associated genes across cells and tissue types
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/115836deb7f1469a99809dc9b0f95de5
work_keys_str_mv	AT surajkjaladanki geneticdependencyofalzheimersdiseaseassociatedgenesacrosscellsandtissuetypes AT abdulkadirelmas geneticdependencyofalzheimersdiseaseassociatedgenesacrosscellsandtissuetypes AT gabrielsantosmalave geneticdependencyofalzheimersdiseaseassociatedgenesacrosscellsandtissuetypes AT kuanlinhuang geneticdependencyofalzheimersdiseaseassociatedgenesacrosscellsandtissuetypes
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Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types

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