Evaluation of DNA repair efficiency in autistic children by molecular cytogenetic analysis and transcriptome profiling

Abstract

Data regarding DNA repair perturbations in autism, which might increase the risk of malignancy, are scarce. To evaluate whether DNA repair may be disrupted in autistic children, we assessed the incidence of endogenous basal DNA strand breaks as well as the efficiency of repairing DNA damage caused by γ-ray in lymphocytes isolated from autistic and healthy children. The incidence of DNA damage and the kinetics of DNA repair were determined by comet assay, while the incidence of residual DNA damage was evaluated by structural chromosomal aberration analysis. Transcriptome profiling of 84 genes associated with DNA damage and repair-signaling pathways was performed by RT² Profiler PCR Array. The array data were confirmed by RT-PCR and western blot studies. Our data indicate that the incidence of basal oxidative DNA strand breaks in autistic children was greater than that in nonautistic controls. Lymphocytes from autistic children displayed higher susceptibility to damage by γ-irradiation and slower repair rate than those from nonautistic children. Although the total unstable chromosomal aberrations were unaffected, lymphocytes from autistic children were more susceptible to chromosomal damage caused by γ-ray than those from nonautistic children. Transcriptomic analysis revealed that several genes associated with repair were downregulated in lymphocytes from autistic individuals and in those exposed to γ-irradiation. This may explain the increased oxidative DNA damage and reduced repair rate in lymphocytes from autistic individuals. These features may be related to the possible correlation between autism and the elevated risk of cancer and may explain the role of the disruption of the DNA repair process in the pathogenesis of autism.