期刊
BIOLOGY DIRECT
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1745-6150-9-16
关键词
Synonymous mutations; Single nucleotide polymorphism; Codon usage; Splicing enhancer; Splicing silencer; mRNA secondary structure; Transcription factor binding; Neurotoxin
类别
资金
- Intramural Research Program of the National Eye Institute
- Intramural Research Program of the National Library of Medicine at the National Institutes of Health (US Department Health and Human Services)
Background: A dramatic increase in the prevalence of autism and Autistic Spectrum Disorders (ASD) has been observed over the last two decades in USA, Europe and Asia. Given the accumulating data on the possible role of translation in the etiology of ASD, we analyzed potential effects of rare synonymous substitutions associated with ASD on mRNA stability, splicing enhancers and silencers, and codon usage. Presentation of the hypothesis: We hypothesize that subtle impairment of translation, resulting in dosage imbalance of neuron-specific proteins, contributes to the etiology of ASD synergistically with environmental neurotoxins. Testing the hypothesis: A statistically significant shift from optimal to suboptimal codons caused by rare synonymous substitutions associated with ASD was detected whereas no effect on other analyzed characteristics of transcripts was identified. This result suggests that the impact of rare codons on the translation of genes involved in neuron development, even if slight in magnitude, could contribute to the pathogenesis of ASD in the presence of an aggressive chemical background. This hypothesis could be tested by further analysis of ASD-associated mutations, direct biochemical characterization of their effects, and assessment of in vivo effects on animal models.
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