Ribosomal DNA Abundance in the Patient's Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia

Abstract

Introduction: Differential diagnostics of early-onset schizophrenia and autism spectrum disorders (ASD) are a problem of child psychiatry. The prognosis and relevant treatment are to a large degree determined by the correctness of diagnosis. We found earlier that leucocyte DNA of adult schizophrenia patients contained significantly larger copy numbers of ribosomal repeats (rDNA) coding for rRNA, than DNA of mentally healthy controls. Aim: To compare the contents of ribosomal repeats in the leucocyte DNA of children with schizophrenia, children with ASD, and healthy age-matched controls to estimate the possibility of using this genetic trait in the differential diagnostics of the two types of disorders. Patients and methods: Blood samples of patients with infantile autism (A—F84.0 according to ICD-10, N = 75) and with childhood-onset schizophrenia (SZ—F20.8 according to ICD-10, N = 43) were obtained from the Child Psychiatry Department of the Mental Health Research Center. The healthy control blood samples (HC, N = 86) were taken from the Research Centre for Medical Genetics collection. The recruitment of cases was based on the clinical psychopathologic approach. DNA was extracted from blood leukocytes with organic solvents. Nonradioactive quantitative hybridization technique was applied for determining the abundance of ribosomal repeats in the genomes. Statistical processing was performed using StatPlus, Statgraphics and MedCalc. Findings: DNA derived from SZ cases contained 565 ± 163 rDNA copies, which is significantly (p < 10−6) higher than the rDNA content in ASD cases (405 ± 109 copies) and controls (403 ± 86 copies). The HC and A groups did not differ by rDNA copy number (p > 0.4). The genetic trait “rDNA copy number in patient’s genome” can potentially be applied as an additional marker in differential diagnostics of childhood-onset schizophrenia and autism spectrum disorders.

Keywords: ASD; childhood-onset schizophrenia; copy number; early-onset schizophrenia; infantile autism; ribosomal genes.

Figure 1

(A). Location of genes for rRNA on human chromosomes. Scheme of the ribosomal repeat unit. The area is shown that can be detected using a biotinylated DNA probe for rDNA. (B). The values of rDNA abundance obtained in the experiment for the three cohorts of children. (C). Comparison of the groups by rDNA CN distribution. The arrows indicate the groups compared, and the frames shows the statistical analysis data. (D,E). Logistic curves and ROC curves drawn for the groups of ill children compared to the controls.