Plant 45S rDNA Clusters Are Fragile Sites and Their Instability Is Associated with Epigenetic Alterations

Our previous study demonstrated that 45S ribosomal DNA (45S rDNA) clusters were chromosome fragile sites expressed spontaneously in Lolium. In this study, fragile phenotypes of 45S rDNA were observed under aphidicolin (APH) incubation in several plant species. Further actinomycin D (ActD) treatment showed that transcriptional stress might interfere with chromatin packaging, resulting in 45S rDNA fragile expression. These data identified 45S rDNA sites as replication-dependent as well as transcription-dependent fragile sites in plants. In the presence of ActD, a dramatic switch to an open chromatin conformation and accumulated incomplete 5′ end of the external transcribed spacer (5′ETS) transcripts were observed, accompanied by decreased DNA methylation, decreased levels of histone H3, and increased histone acetylation and levels of H3K4me2, suggesting that these epigenetic alterations are associated with failure of 45S rDNA condensation. Furthermore, the finding that γ-H2AX was accumulated at 45S rDNA sites following ActD treatment suggested that the DNA damage signaling pathway was associated with the appearance of 45S rDNA fragile phenotypes. Our data provide a link between 45S rDNA transcription and chromatin-packaging defects and open the door for further identifying the molecular mechanism involved

Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings.

Background: Schizotypy, or the set of personality traits related to schizophrenia, is considered an endophenotypic manifestation that is more represented in first-degree relatives of patients with schizophrenia than in the general population. The assessment of schizotypy is primarily based on self-reports, and for this reason it presents several limitations. In order to assess schizotypy, this study proposes a diagnostic instrument based on clinical reports. Methods: A sample of 66 subjects, composed of 25 outpatients with schizophrenia, 18 siblings of these patients and 23 healthy controls, was subjected to the personality assessment test SWAP-200 by trained clinical interviewers. To test the hypothesis of the difference between the profiles of the Personality Disorders within the schizophrenia spectrum, a Multivariate Analysis of Variance and subsequent planned comparisons were conducted. Results: Patients with schizophrenia scored higher than both their siblings and the controls on all SWAP-200 scales; their siblings, compared to the healthy controls, showed significant statistical differences, with higher mean scores for paranoid (F-(1,F-63) = 7.02; p = 0.01), schizoid (F-(1,F-63) = 6.56; p = 0.013) and schizotypal (F-(1,F-63) = 6.47; p = 0.013) traits (PD T scores of Cluster A and Q-factor scores for the schizoid scale [F-(1,F-63) = 6.47; p = 0.013]). Conclusions: Consistent with previous data, first-degree relatives of patients with schizophrenia scored higher on schizophrenia-related personality traits than a general population comparison sample. SWAP-200, as an alternative diagnostic instrument to self-report measures, is able to reveal the higher prevalence of schizotypal traits in siblings of patients with schizophrenia, suggesting its possible use as a complementary instrument for the assessment of schizophrenia