Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder.
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4511766?pdf=render |
| _version_ | 1828734940946104320 |
|---|---|
| author | Maria Jalbrzikowski Maria T Lazaro Fuying Gao Alden Huang Carolyn Chow Daniel H Geschwind Giovanni Coppola Carrie E Bearden |
| author_facet | Maria Jalbrzikowski Maria T Lazaro Fuying Gao Alden Huang Carolyn Chow Daniel H Geschwind Giovanni Coppola Carrie E Bearden |
| author_sort | Maria Jalbrzikowski |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-04-12T22:56:55Z |
| format | Article |
| id | doaj.art-7f1a0a110004421fb4fff216bbf3f2ea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T22:56:55Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7f1a0a110004421fb4fff216bbf3f2ea2022-12-22T03:13:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013254210.1371/journal.pone.0132542Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder.Maria JalbrzikowskiMaria T LazaroFuying GaoAlden HuangCarolyn ChowDaniel H GeschwindGiovanni CoppolaCarrie E Bearden22q11.2 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.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.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.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.http://europepmc.org/articles/PMC4511766?pdf=render |
| spellingShingle | Maria Jalbrzikowski Maria T Lazaro Fuying Gao Alden Huang Carolyn Chow Daniel H Geschwind Giovanni Coppola Carrie E Bearden Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. PLoS ONE |
| title | Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. |
| title_full | Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. |
| title_fullStr | Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. |
| title_full_unstemmed | Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. |
| title_short | Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder. |
| title_sort | transcriptome profiling of peripheral blood in 22q11 2 deletion syndrome reveals functional pathways related to psychosis and autism spectrum disorder |
| url | http://europepmc.org/articles/PMC4511766?pdf=render |
| work_keys_str_mv | AT mariajalbrzikowski transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT mariatlazaro transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT fuyinggao transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT aldenhuang transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT carolynchow transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT danielhgeschwind transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT giovannicoppola transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder AT carrieebearden transcriptomeprofilingofperipheralbloodin22q112deletionsyndromerevealsfunctionalpathwaysrelatedtopsychosisandautismspectrumdisorder |