Format

Send to

Choose Destination
G3 (Bethesda). 2018 Mar 2;8(3):967-979. doi: 10.1534/g3.118.200019.

Systematic Functional Characterization of Human 21st Chromosome Orthologs in Caenorhabditis elegans.

Author information

1
Institute for Neuroscience, Department of Neuroscience, The University of Texas at Austin, Texas 78712.
2
Institute for Neuroscience, Department of Neuroscience, The University of Texas at Austin, Texas 78712 jonps@austin.utexas.edu.
3
Institute for Cellular and Molecular Biology, Department of Neuroscience, The University of Texas at Austin, Texas 78712.
4
Center for Learning and Memory, Department of Neuroscience, The University of Texas at Austin, Texas 78712.
5
Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, The University of Texas at Austin, Texas 78712.

Abstract

Individuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21st chromosome (HSA21). Only a few of ∼200 HSA21 genes encoding proteins have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode Caenorhabditis elegans We identified 10 HSA21 orthologs that are required for neuromuscular behaviors: cle-1 (COL18A1), cysl-2 (CBS), dnsn-1 (DONSON), eva-1 (EVA1C), mtq-2 (N6ATM1), ncam-1 (NCAM2), pad-2 (POFUT2), pdxk-1 (PDXK), rnt-1 (RUNX1), and unc-26 (SYNJ1). We also found that three of these genes are required for normal release of the neurotransmitter acetylcholine. This includes a known synaptic gene unc-26 (SYNJ1), as well as uncharacterized genes pdxk-1 (PDXK) and mtq-2 (N6ATM1). As the first systematic functional analysis of HSA21 orthologs, this study may serve as a platform to understand genes that underlie phenotypes associated with Down syndrome.

KEYWORDS:

Down syndrome; neurological; neuromuscular; synaptic

PMID:
29367452
PMCID:
PMC5844316
DOI:
10.1534/g3.118.200019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center