10.1371/journal.pone.0132542
Maria Jalbrzikowski
Maria
Jalbrzikowski
Maria T. Lazaro
Maria
T. Lazaro
Fuying Gao
Fuying
Gao
Alden Huang
Alden
Huang
Carolyn Chow
Carolyn
Chow
Daniel H. Geschwind
Daniel
H. Geschwind
Giovanni Coppola
Giovanni
Coppola
Carrie E. Bearden
Carrie
E. Bearden
Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder
Public Library of Science
2015
idiopathic psychosis
expression changes
antipsychotic medication use
risk factors
22 q 11.2 Deletion Syndrome
response pathways
WGCNA analyses
ht
transcriptional regulation
idiopathic ASD.ConclusionThese findings
Functional Pathways Related
brain tissue
22 q 11DS patients
gene
idiopathic schizophrenia
22 q 11DS
peripheral blood
deletion characteristics
22 q 11DS individuals
pathways dysregulated
22 q 11DS carriers
module
Transcriptome Profiling
3 Mb deletion
data mining techniques
deletion breakpoints
de
Genomic Analyses
phenotypic variation
aCGH array
spectrum disorders
transcriptional changes
2015-07-22 03:02:56
Dataset
https://plos.figshare.com/articles/dataset/_Transcriptome_Profiling_of_Peripheral_Blood_in_22q11_2_Deletion_Syndrome_Reveals_Functional_Pathways_Related_to_Psychosis_and_Autism_Spectrum_Disorder_/1491728
<div><p>Background</p><p>22q11.2 Deletion Syndrome (22q11DS) represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD) in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes.</p><p>Methods</p><p>We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential expression (DE) and networks of co-expressed genes related to phenotypic variation within 22q11DS patients. Whole-genome transcriptional profiling was performed using Illumina Human HT-12 microarrays. Data mining techniques were used to validate our results against independent samples of both peripheral blood and brain tissue from idiopathic psychosis and ASD cases.</p><p>Results</p><p>Eighty-five percent of 22q11DS individuals (N = 39) carried the typical 3 Mb deletion, with significant variability in deletion characteristics in the remainder of the sample (N = 7). DE analysis and weighted gene co-expression network analysis (WGCNA) identified expression changes related to psychotic symptoms in patients, including a module of co-expressed genes which was associated with psychosis in 22q11DS and involved in pathways associated with transcriptional regulation. This module was enriched for brain-expressed genes, was not related to antipsychotic medication use, and significantly overlapped with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE and WGCNA analyses implicated dysregulation of immune response pathways. The ASD-associated module showed significant overlap with genes previously associated with idiopathic ASD.</p><p>Conclusion</p><p>These findings further support the use of peripheral tissue in the study of major mutational models of diseases affecting the brain, and point towards specific pathways dysregulated in 22q11DS carriers with psychosis and ASD.</p></div>