# Autism risk variants in DLG4 ortholog increase penetrance of uncommon individual behavioral trait in Caenorhabditis elegans

## TL;DR

This study shows that a genetic variant linked to autism in humans increases a specific unusual behavior in worms, offering a model for understanding how such variants affect behavior.

## Contribution

The study demonstrates how an autism risk variant in DLG4 increases the penetrance of a rare behavioral trait in C. elegans.

## Key findings

- 30% of wild-type worms display conducting behavior, while 50% of dlg-1 mutants show it.
- The increased conducting behavior in dlg-1 mutants is recessive and can be rescued with the wild-type gene.
- Another DLG4 patient variant phenocopies the increased conducting behavior in worms.

## Abstract

Autism is a largely neurogenetic condition characterized by atypical behaviors, including increased prevalence of motor stereotypies. We used

Caenorhabditis elegans

to model the T611I variant in the
DLG4
ortholog

dlg-1

. During phenotyping, we found that some worms intersperse typical dorsoventral swimming bends with left-right bends, resembling an orchestra conductor's arm motions. Conducting behavior occurred in 30% of wild-type but 50% of

dlg-1

mutant worms. The high proportion of conducting in

dlg-1

is recessive, rescuable with the wild-type gene, and phenocopied with another
DLG4
patient variant. This provides an example of autism variants increasing the proportion of a low-penetrant individual behavior.