publication . Article . 2014

MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome

Merico, Daniele; Costain, Gregory; Butcher, Nancy J.; Warnica, William; Ogura, Lucas; Alfred, Simon E.; Brzustowicz, Linda M.; Bassett, Anne S.;
Open Access English
  • Published: 01 Nov 2014 Journal: Frontiers in Neurology, volume 5 (issn: 1664-2295, eissn: 1664-2295, Copyright policy)
  • Publisher: Frontiers Media S.A.
Abstract
The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA gen...
Subjects
free text keywords: protein interaction network, Neuroscience, DGCR8, miRNA, Original Research, schizophrenia, synapse, 22q11.2, 22q11 deletion, DiGeorge syndrome
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH090047-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH089921-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH089929-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
83 references, page 1 of 6

1 Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol (2005) 6:376–85.10.1038/nrm1644 15852042 [PubMed] [DOI]

2 Maffioletti E Tardito D Gennarelli M Bocchio-Chiavetto L. Micro spies from the brain to the periphery: new clues from studies on microRNAs in neuropsychiatric disorders. Front Cell Neurosci (2014) 8:75.10.3389/fncel.2014.00075 24653674 [OpenAIRE] [PubMed] [DOI]

3 Bassett AS McDonald-McGinn DM Devriendt K Digilio MC Goldenberg P Habel A Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr (2011) 159(332–9):e1.10.1016/j.jpeds.2011.02.039 [OpenAIRE] [DOI]

4 Costain G McDonald-McGinn DM Bassett AS. Prenatal genetic testing with chromosomal microarray analysis identifies major risk variants for schizophrenia and other later-onset disorders. Am J Psychiatry (2013) 170:1498.10.1176/appi.ajp.2013.13070880 [OpenAIRE] [DOI]

5 Kaminsky EB Kaul V Paschall J Church DM Bunke B Kunig D An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med (2011) 13:777–84.10.1097/GIM.0b013e31822c79f9 21844811 [OpenAIRE] [PubMed] [DOI]

6 Costain G Bassett AS. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era. Appl Clin Genet (2012) 5:1–18.10.2147/TACG.S21953 23144566 [OpenAIRE] [PubMed] [DOI]

7 Fung WL McEvilly R Fong J Silversides C Chow E Bassett A. Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome. Am J Psychiatry (2010) 167:998.10.1176/appi.ajp.2010.09101463 [OpenAIRE] [DOI]

8 Bassett AS Costain G Alan Fung WL Russell KJ Pierce L Kapadia R Clinically detec table copy number variations in a Canadian catchment population of schizophrenia. J Psychiatr Res (2010) 44:1005–9.10.1016/j.jpsychires.2010.06.013 20643418 [OpenAIRE] [PubMed] [DOI]

9 Perkins DO Jeffries CD Jarskog LF Thomson JM Woods K Newman MA microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol (2007) 8:R27.10.1186/gb-2007-8-2-r27 17326821 [OpenAIRE] [PubMed] [DOI]

10 Beveridge NJ Tooney PA Carroll AP Gardiner E Bowden N Scott RJ Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet (2008) 17:1156–68.10.1093/hmg/ddn005 18184693 [PubMed] [DOI]

11 Dean B Boer S Gibbons A Money T Scarr E. Recent advances in postmortem pathology and neurochemistry in schizophrenia. Curr Opin Psychiatry (2009) 22:154–60.10.1097/YCO.0b013e328323d52e 19553869 [PubMed] [DOI]

12 Kim AH Reimers M Maher B Williamson V McMichael O McClay JL MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res (2010) 124:183–91.10.1016/j.schres.2010.07.002 20675101 [OpenAIRE] [PubMed] [DOI]

13 Moreau MP Bruse SE Da vid-Rus R Buyske S Brzustowicz LM. Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry (2011) 69:188–93.10.1016/j.biopsych.2010.09.039 21183010 [OpenAIRE] [PubMed] [DOI]

14 Santarelli DM Beveridge NJ Tooney PA Cairns MJ. Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry (2011) 69:180–7.10.1016/j.biopsych.2010.09.030 21111402 [PubMed] [DOI]

15 Beveridge NJ Santarelli DM Wang X Tooney PA Webster MJ Weickert CS Maturation of the human dorsolateral prefrontal cortex coincides with a dynamic shift in microRNA expression. Schizophr Bull (2013) 40:399–409.10.1093/schbul/sbs198 23378013 [OpenAIRE] [PubMed] [DOI]

83 references, page 1 of 6
Abstract
The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA gen...
Subjects
free text keywords: protein interaction network, Neuroscience, DGCR8, miRNA, Original Research, schizophrenia, synapse, 22q11.2, 22q11 deletion, DiGeorge syndrome
Funded by
CIHR
Project
  • Funder: Canadian Institutes of Health Research (CIHR)
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH090047-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH089921-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
NIH| Transcriptional Atlas of Human Brain Development
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1RC2MH089929-01
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
83 references, page 1 of 6

1 Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol (2005) 6:376–85.10.1038/nrm1644 15852042 [PubMed] [DOI]

2 Maffioletti E Tardito D Gennarelli M Bocchio-Chiavetto L. Micro spies from the brain to the periphery: new clues from studies on microRNAs in neuropsychiatric disorders. Front Cell Neurosci (2014) 8:75.10.3389/fncel.2014.00075 24653674 [OpenAIRE] [PubMed] [DOI]

3 Bassett AS McDonald-McGinn DM Devriendt K Digilio MC Goldenberg P Habel A Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr (2011) 159(332–9):e1.10.1016/j.jpeds.2011.02.039 [OpenAIRE] [DOI]

4 Costain G McDonald-McGinn DM Bassett AS. Prenatal genetic testing with chromosomal microarray analysis identifies major risk variants for schizophrenia and other later-onset disorders. Am J Psychiatry (2013) 170:1498.10.1176/appi.ajp.2013.13070880 [OpenAIRE] [DOI]

5 Kaminsky EB Kaul V Paschall J Church DM Bunke B Kunig D An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med (2011) 13:777–84.10.1097/GIM.0b013e31822c79f9 21844811 [OpenAIRE] [PubMed] [DOI]

6 Costain G Bassett AS. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era. Appl Clin Genet (2012) 5:1–18.10.2147/TACG.S21953 23144566 [OpenAIRE] [PubMed] [DOI]

7 Fung WL McEvilly R Fong J Silversides C Chow E Bassett A. Elevated prevalence of generalized anxiety disorder in adults with 22q11.2 deletion syndrome. Am J Psychiatry (2010) 167:998.10.1176/appi.ajp.2010.09101463 [OpenAIRE] [DOI]

8 Bassett AS Costain G Alan Fung WL Russell KJ Pierce L Kapadia R Clinically detec table copy number variations in a Canadian catchment population of schizophrenia. J Psychiatr Res (2010) 44:1005–9.10.1016/j.jpsychires.2010.06.013 20643418 [OpenAIRE] [PubMed] [DOI]

9 Perkins DO Jeffries CD Jarskog LF Thomson JM Woods K Newman MA microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol (2007) 8:R27.10.1186/gb-2007-8-2-r27 17326821 [OpenAIRE] [PubMed] [DOI]

10 Beveridge NJ Tooney PA Carroll AP Gardiner E Bowden N Scott RJ Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet (2008) 17:1156–68.10.1093/hmg/ddn005 18184693 [PubMed] [DOI]

11 Dean B Boer S Gibbons A Money T Scarr E. Recent advances in postmortem pathology and neurochemistry in schizophrenia. Curr Opin Psychiatry (2009) 22:154–60.10.1097/YCO.0b013e328323d52e 19553869 [PubMed] [DOI]

12 Kim AH Reimers M Maher B Williamson V McMichael O McClay JL MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res (2010) 124:183–91.10.1016/j.schres.2010.07.002 20675101 [OpenAIRE] [PubMed] [DOI]

13 Moreau MP Bruse SE Da vid-Rus R Buyske S Brzustowicz LM. Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry (2011) 69:188–93.10.1016/j.biopsych.2010.09.039 21183010 [OpenAIRE] [PubMed] [DOI]

14 Santarelli DM Beveridge NJ Tooney PA Cairns MJ. Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry (2011) 69:180–7.10.1016/j.biopsych.2010.09.030 21111402 [PubMed] [DOI]

15 Beveridge NJ Santarelli DM Wang X Tooney PA Webster MJ Weickert CS Maturation of the human dorsolateral prefrontal cortex coincides with a dynamic shift in microRNA expression. Schizophr Bull (2013) 40:399–409.10.1093/schbul/sbs198 23378013 [OpenAIRE] [PubMed] [DOI]

83 references, page 1 of 6
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publication . Article . 2014

MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome

Merico, Daniele; Costain, Gregory; Butcher, Nancy J.; Warnica, William; Ogura, Lucas; Alfred, Simon E.; Brzustowicz, Linda M.; Bassett, Anne S.;