RRC ID 51555
Author Nordquist SK, Smith SR, Pierce JT.
Title Systematic Functional Characterization of Human 21st Chromosome Orthologs in Caenorhabditis elegans.
Journal G3 (Bethesda)
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.
Volume 8(3)
Pages 967-979
Published 2018-3-2
DOI 10.1534/g3.118.200019
PII g3.118.200019
PMID 29367452
PMC PMC5844316
MeSH Animals Animals, Genetically Modified Behavior, Animal Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Chromosomes, Human, Pair 21* Disease Models, Animal Down Syndrome / diagnosis Down Syndrome / genetics* Genetic Association Studies Humans Mutation* Neuromuscular Junction / physiopathology Open Reading Frames Phenotype RNA Interference
IF 2.781
Times Cited 4
C.elegans tm1146 tm1756 tm2626 tm2657 tm3322 tm3565 tm6706 tm776