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Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour

Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour
Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organism C. elegans provides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulate C. elegans food leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identify C. elegans orthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism in C. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.
1932-6203
Rawsthorne-Manning, Helena
17228f7b-6d7b-4f73-9dbc-6849c3f1f496
Calahorro Nunez, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Holden-Dye, Linda
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed
Rawsthorne-Manning, Helena
17228f7b-6d7b-4f73-9dbc-6849c3f1f496
Calahorro Nunez, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Holden-Dye, Linda
8032bf60-5db6-40cb-b71c-ddda9d212c8e
O'connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Dillon, James
f406e30a-3ad4-4a53-80db-6694bab5e3ed

Rawsthorne-Manning, Helena, Calahorro Nunez, Fernando, Holden-Dye, Linda, O'connor, Vincent and Dillon, James (2021) Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour. PLoS ONE, 16, [e0243121]. (doi:10.1371/journal.pone.0243121).

Record type: Article

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organism C. elegans provides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulate C. elegans food leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identify C. elegans orthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism in C. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.

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journal.pone.0243121 - Version of Record
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Accepted/In Press date: 29 March 2021
Published date: 27 May 2021
Additional Information: Publisher Copyright: Copyright: © 2021 Rawsthorne et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 449921
URI: http://eprints.soton.ac.uk/id/eprint/449921
ISSN: 1932-6203
PURE UUID: 5466e84f-b05c-4d31-af1c-834f9be9bfc5
ORCID for Fernando Calahorro Nunez: ORCID iD orcid.org/0000-0003-0659-7728
ORCID for Linda Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217

Catalogue record

Date deposited: 25 Jun 2021 16:31
Last modified: 26 Nov 2021 03:00

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Contributors

Author: Helena Rawsthorne-Manning
Author: James Dillon

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