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

G3: Genes, Genomes, Genetics

Jonathan T. Pierce^2²  Sofia R. Smith^1³  Sarah K. Nordquist^1⁴ 

[1] Center for Learning and Memory, Department of Neuroscience, The University of Texas at Austin, Texas 78712;Institute for Cellular and Molecular Biology, Department of Neuroscience, The University of Texas at Austin, Texas 78712;Institute for Neuroscience, Department of Neuroscience, The University of Texas at Austin, Texas 78712;Institute for Neuroscience, Department of Neuroscience, The University of Texas at Austin, Texas 78712^1;Waggoner Center for Alcohol and Addiction Research, Department of Neuroscience, The University of Texas at Austin, Texas 78712^2

关键词: Down syndrome;    neuromuscular;    neurological;    synaptic;   

DOI  :  10.1534/g3.118.200019

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

CC BY