The Drosophila Gene Sulfateless Modulates Autism-Like Behaviors
Major challenges to identifying genes that contribute to autism spectrum disorder (ASD) risk include the availability of large ASD cohorts, the contribution of many genes overall, and small effect sizes attributable to common gene variants. An alternative approach is to use a model organism to detec...
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| Published in: | Frontiers in genetics Vol. 10; p. 574 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
19-06-2019
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Major challenges to identifying genes that contribute to autism spectrum disorder (ASD) risk include the availability of large ASD cohorts, the contribution of many genes overall, and small effect sizes attributable to common gene variants. An alternative approach is to use a model organism to detect alleles that impact ASD-relevant behaviors and ask whether homologous human genes infer ASD risk. Here we utilized the Drosophila genetic reference panel (DGRP) as a tool to probe for perturbation in naturally occurring behaviors in
that are analogous to three behavior domains: impaired social communication, social reciprocity and repetitive behaviors or restricted interests. Using 40 of the available DGRP lines, we identified single nucleotide polymorphisms (SNPs) in or near genes controlling these behavior domains, including ASD gene orthologs (
and
), an intellectual disability (ID) gene homolog (
), and a gene encoding a heparan sulfate (HS) modifying enzyme called
(
). SNPs in
were associated with all three ASD-like behaviors. Using RNAi knock-down of neuronal
expression, we observed significant changes in expressive and receptive communication during mating, decreased grooming behavior, and increased social spacing. These results suggest a role for HS proteoglycan synthesis and/or modification in normal social communication, repetitive behavior, and social interaction in flies. Finally, using the DGRP to directly identify genetic effects relevant to a neuropsychiatric disorder further demonstrates the utility of the Drosophila system in the discovery of genes relevant to human disease. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Erica E. Davis, Duke University, United States This article was submitted to Genetic Disorders, a section of the journal Frontiers in Genetics Reviewed by: Santhosh Girirajan, Pennsylvania State University, United States; Annette Schenck, Radboud University Nijmegen Medical Centre, Netherlands |
| ISSN: | 1664-8021 1664-8021 |
| DOI: | 10.3389/fgene.2019.00574 |