Turning strains into strengths for understanding psychiatric disorders
There is a paucity in the development of new mechanistic insights and therapeutic approaches for treating psychiatric disease. One of the major challenges is reflected in the growing consensus that risk for these diseases is not determined by a single gene, but rather is polygenic, arising from the...
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Veröffentlicht in: | Molecular psychiatry 2020-12, Vol.25 (12), p.3164-3177 |
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description | There is a paucity in the development of new mechanistic insights and therapeutic approaches for treating psychiatric disease. One of the major challenges is reflected in the growing consensus that risk for these diseases is not determined by a single gene, but rather is polygenic, arising from the action and interaction of multiple genes. Canonically, experimental models in mice have been designed to ascertain the relative contribution of a single gene to a disease by systematic manipulation (e.g., mutation or deletion) of a known candidate gene. Because these studies have been largely carried out using inbred isogenic mouse strains, in which there is no (or very little) genetic diversity among subjects, it is difficult to identify unique allelic variants, gene modifiers, and epigenetic factors that strongly affect the nature and severity of these diseases. Here, we review various methods that take advantage of existing genetic diversity or that increase genetic variance in mouse models to (1) strengthen conclusions of single-gene function; (2) model diversity among human populations; and (3) dissect complex phenotypes that arise from the actions of multiple genes. |
doi_str_mv | 10.1038/s41380-020-0772-y |
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One of the major challenges is reflected in the growing consensus that risk for these diseases is not determined by a single gene, but rather is polygenic, arising from the action and interaction of multiple genes. Canonically, experimental models in mice have been designed to ascertain the relative contribution of a single gene to a disease by systematic manipulation (e.g., mutation or deletion) of a known candidate gene. Because these studies have been largely carried out using inbred isogenic mouse strains, in which there is no (or very little) genetic diversity among subjects, it is difficult to identify unique allelic variants, gene modifiers, and epigenetic factors that strongly affect the nature and severity of these diseases. 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Murphy, Geoffrey G. ; Cazares, Victor A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-27a8a5ba7be16ad62382624d211408ba6610d8acc7f06d0555a944f5c4f4a1493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>38/43</topic><topic>45/23</topic><topic>45/41</topic><topic>631/208</topic><topic>631/378</topic><topic>64/110</topic><topic>64/60</topic><topic>692/699/476</topic><topic>Alleles</topic><topic>Animal models</topic><topic>Animals</topic><topic>Behavioral Sciences</topic><topic>Biological diversity</topic><topic>Biological Psychology</topic><topic>Diagnosis</topic><topic>Epigenetics</topic><topic>Gene deletion</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic engineering</topic><topic>Inbreeding</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental disorders</topic><topic>Mental Disorders - genetics</topic><topic>Mental illness</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Multifactorial Inheritance - genetics</topic><topic>Neurosciences</topic><topic>Pharmacotherapy</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Psychiatric research</topic><topic>Psychiatry</topic><topic>Review Article</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moore, Shannon J.</creatorcontrib><creatorcontrib>Murphy, Geoffrey G.</creatorcontrib><creatorcontrib>Cazares, Victor A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moore, Shannon J.</au><au>Murphy, Geoffrey G.</au><au>Cazares, Victor A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Turning strains into strengths for understanding psychiatric disorders</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>25</volume><issue>12</issue><spage>3164</spage><epage>3177</epage><pages>3164-3177</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>There is a paucity in the development of new mechanistic insights and therapeutic approaches for treating psychiatric disease. 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title | Turning strains into strengths for understanding psychiatric disorders |
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