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Article

New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork

1
Department of Biotechnology, Chaitanya Bharathi Institute of Technology, Hyderabad 500075, India
2
Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jason Bubier
Genes 2022, 13(4), 614; https://doi.org/10.3390/genes13040614
Received: 2 February 2022 / Revised: 2 March 2022 / Accepted: 7 March 2022 / Published: 29 March 2022
(This article belongs to the Special Issue Genetics and Genomics of Addiction)
Gene-by-environment interactions are important for all facets of biology, especially behaviour. Families of isogenic strains of mice, such as the BXD strains, are excellently placed to study these interactions, as the same genome can be tested in multiple environments. BXD strains are recombinant inbred mouse strains derived from crossing two inbred strains—C57BL/6J and DBA/2J mice. Many reproducible genometypes can be leveraged, and old data can be reanalysed with new tools to produce novel insights. We obtained drug and behavioural phenotypes from Philip et al. Genes, Brain and Behaviour 2010, and reanalysed their data with new genotypes from sequencing, as well as new models (Genome-wide Efficient Mixed Model Association (GEMMA) and R/qtl2). We discovered QTLs on chromosomes 3, 5, 9, 11, and 14, not found in the original study. We reduced the candidate genes based on their ability to alter gene expression or protein function. Candidate genes included Slitrk6 and Cdk14. Slitrk6, in a Chromosome14 QTL for locomotion, was found to be part of a co-expression network involved in voluntary movement and associated with neuropsychiatric phenotypes. Cdk14, one of only three genes in a Chromosome5 QTL, is associated with handling induced convulsions after ethanol treatment, that is regulated by the anticonvulsant drug valproic acid. By using families of isogenic strains, we can reanalyse data to discover novel candidate genes involved in response to drugs of abuse. View Full-Text
Keywords: addiction; human genetics; systems genetics; gene expression; bioinformatics; cross-species analysis; animal models; genomics; genetic mapping addiction; human genetics; systems genetics; gene expression; bioinformatics; cross-species analysis; animal models; genomics; genetic mapping
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MDPI and ACS Style

Chunduri, A.; Watson, P.M.; Ashbrook, D.G. New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork. Genes 2022, 13, 614. https://doi.org/10.3390/genes13040614

AMA Style

Chunduri A, Watson PM, Ashbrook DG. New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork. Genes. 2022; 13(4):614. https://doi.org/10.3390/genes13040614

Chicago/Turabian Style

Chunduri, Alisha, Pamela M. Watson, and David G. Ashbrook. 2022. "New Insights on Gene by Environmental Effects of Drugs of Abuse in Animal Models Using GeneNetwork" Genes 13, no. 4: 614. https://doi.org/10.3390/genes13040614

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