👤 Gabriel R Fries

Gene expression alterations have been implicated in suicide pathology. However, the study of the regulatory effect of DNA methylation on gene expression in the suicidal brain has been restricted to candidate genes. The objective of the study was to identify genes whose expression levels are correlated with DNA methylation in the prefrontal cortex of suicides. Postmortem prefrontal cortex samples from 21 suicides and six non-suicides were collected. Transcriptomic and DNA methylation profiles were evaluated with microarrays; cis correlations between gene expression and CpG methylation were screened. We then analyzed the presence of transcription factor (TF) binding sites (TFBS) at CpG sites correlated with gene expression. Gene expression of TFs involved in neurodevelopmental binding to predicted TFBS was determined in the BrainSpan database. We identified 22 CpG sites whose methylation levels correlated with gene expression in the prefrontal cortex of suicides. Genes annotated to identified CpG sites were involved in neurodevelopment (BBS4, NKX6-2, AXL, CTNND1, and MBP) and polyamine metabolism (polyamine oxidase [PAOX]). Such correlations were not detected in the nonsuicide group. Nine TFs (USF1, TBP, SF1, NRF1, RFX1, SP3, PKNOX1, MAZ, and POU3F2) showed differential expression in pre- and post-natal developmental periods, according to BrainSpan database. The integration of different omic technologies provided novel candidates for the investigation of genes whose expression is altered in the suicidal brain and their potential regulatory mechanisms. Show less

An autosomal dominant mutation has been identified in the myosin-binding protein C (MYBPC3) gene of Maine Coon cats. This mutation changes a conserved amino acid and computationally alters the protein conformation of this gene in Maine Coon cats with hypertrophic cardiomyopathy. The prevalence of this mutation is unknown. To determine the genetic prevalence of the MYBPC3 mutation in a large cohort of predominantly Maine Coon cats. Three thousand three hundred and ten DNA samples (blood or buccal swab) from cats. This retrospective study reviewed the Veterinary Cardiac Genetics Laboratory database at Washington State University for samples submitted for evaluation of the Maine Coon MYBPC3 mutation. The data were analyzed with respect to the breed of cat, mutation status (negative, heterozygous, homozygous), and geographic origin of the submission. In the population of cats studied, Maine Coon cats accounted for 100% of all cats positive for the mutation, and the worldwide percentage of Maine Coon cats carrying the MYBPC3 mutation was 34%. The prevalence of the mutation (heterozygous or homozygous) was very similar among countries of submission, suggesting that the 34% mutation rate of the tested samples is a reasonable estimate of the true prevalence of the mutation within the breed. Because of the high prevalence of this mutation, a breeding recommendation to eliminate all cats with the mutation could have a substantial impact on the gene pool. Additional studies are indicated to explore the relationship between genotype and clinical outcome in affected cats. Show less