Evolutionary and Genetic Analysis of Synonymous Nucleotide Substitutions in Subjects with Autism Spectrum Disorders

The director of the project, Dr. Igor Rogozin, analyzed a modest collection of synonymous nucleotide substitutions from two small databases of mutations observed in autistic subjects [1]. Dr. Rogozin and his colleagues found that there was a statistically significant tendency for these synonymous nucleotide substitutions to replace a reference codon supportive of faster protein translation with a non-reference codon that is known to be associated with slower translation [1]. In the proposed study, we wish to test the codon replacement properties of synonymous substitutions reported in the much larger NDAR database, including whether the property of propensity to slower translation holds in a much larger data set of mutations. We also wish to compare the characteristics of the synonymous and nonsynonymous substitutions, using established techniques in genetics.

[1] Poliakov E, Koonin EV, Rogozin IB. Impairment of translation in neurons as a putative causative factor for autism. Biology Direct. 2014; 9:16.