Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome
| Autor: | R, Das Chakraborty, D, Chakraborty, A J, Bernal, K, Schoch, T D, Howard, E H, Ip, S R, Hooper, M S, Keshavan, R L, Jirtle, V, Shashi |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Chromosomes Human Pair 22 Gene Expression Epigenesis Genetic 0302 clinical medicine Reference Values DiGeorge syndrome Imprinting (psychology) Child Genetics 0303 health sciences Extracellular Matrix Proteins Psychopathology Nuclear Proteins Microdeletion syndrome Anxiety Disorders Psychiatry and Mental health Anxiety DGCR6L Female Schizophrenic Psychology Original Article medicine.symptom Chromosome Deletion Psychology Algorithms Adolescent Genotype Polymorphism Single Nucleotide 03 medical and health sciences Cellular and Molecular Neuroscience Genomic Imprinting 22q11DS syndrome DGCR6 medicine DiGeorge Syndrome Humans Abnormalities Multiple Epigenetics Biological Psychiatry 030304 developmental biology epigenetics Computational Biology Proteins Epigenome medicine.disease schizophrenia Behavioral medicine Genomic imprinting 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects. The purpose of this study was to determine if the expression levels of DGCR6 and its duplicate copy DGCR6L in 22q11DS subjects are associated with the parent-of-origin of the deletion and childhood psychopathologies. Our investigation showed no evidence of parent-of-origin-related differences in expression of both DGCR6 and DGCR6L. However, we found that the variability in DGCR6 expression was significantly greater in 22q11DS children than in age and gender-matched control individuals. Children with 22q11DS who had anxiety disorders had significantly lower DGCR6 expression, especially in subjects with the deletion on the maternal chromosome, despite the lack of imprinting. Our findings indicate that epigenetic mechanisms other than imprinting contribute to the dysregulation of these genes and the associated childhood psychopathologies observed in individuals with 22q11DS. Further studies are now needed to test the usefulness of DGCR6 and DGCR6L expression and alterations in the epigenome at these loci in predicting childhood anxiety and associated adult-onset pathologies in 22q11DS subjects. |
| Databáze: | OpenAIRE |
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