Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells

Molecular Psychiatry

Volumn 17, Issue 8, 2012, Pages 827-840

  Gardiner, E ^a,b,c   Beveridge, N J ^a,b,c   Wu, J Q ^a,c   Carr, V ^b,d   Scott, R J ^a,b,c,e   Tooney, P A ^a,b,c   Cairns, M J ^a,b,c  

^a UNIVERSITY OF NEWCASTLE   (Australia)

^b SCHIZOPHRENIA RESEARCH INSTITUTE   (Australia)

^c HUNTER MEDICAL RESEARCH INSTITUTE   (Australia)

^d UNIVERSITY OF NEW SOUTH WALES   (Australia)

^e JOHN HUNTER HOSPITAL   (Australia)

Author keywords

14q32; biomarker; gene silencing; microRNA; PBMCs; schizophrenia

Indexed keywords

MICRORNA;

ADULT; ARTICLE; CHROMOSOME 14Q; CONTROLLED STUDY; DIO3 GENE; DLK1 GENE; DOWN REGULATION; EPIGENETICS; FEMALE; GENE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE LOCUS; GENOME IMPRINTING; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MICROARRAY ANALYSIS; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCHIZOPHRENIA;

ADOLESCENT; ADULT; AGED; BIOLOGICAL MARKERS; CASE-CONTROL STUDIES; CHROMOSOMES, HUMAN, PAIR 14; DNA COPY NUMBER VARIATIONS; DOWN-REGULATION; FEMALE; GENE EXPRESSION PROFILING; GENOMIC IMPRINTING; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MICROARRAY ANALYSIS; MICRORNAS; MIDDLE AGED; SCHIZOPHRENIA;

EID: 84864352823     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2011.78     Document Type: Article

References (103)

1. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med 2005; 2: e141.
2. Nopoulos P, Torres I, Flaum M, Andreasen NC, Ehrhardt JC, Yuh WT. Brain morphology in first-episode schizophrenia. Am J Psychiatry 1995; 152: 1721-1723.
3. Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI findings in schizophrenia. Schizophr Res 2001; 49: 1-52. (Pubitemid 32451739)
4. Weinberger DR, Berman KF, Zec RF. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry 1986; 43: 114-124. (Pubitemid 16163530)
5. McCarley RW, Shenton ME, O'Donnell BF, Faux SF, Kikinis R, Nestor PG et al. Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. Arch Gen Psychiatry 1993; 50: 190-197. (Pubitemid 23077473)
6. Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990; 322: 789-794. (Pubitemid 20094141)
7. Lawrie SM, Hall J, McIntosh AM, Cunningham-Owens DG, Johnstone EC. Neuroimaging and molecular genetics of schizophrenia: pathophysiological advances and therapeutic potential. Br J Pharmacol 2008; 153(Suppl 1): S120-S124. (Pubitemid 351341009)
8. Holmes E, Tsang TM, Huang JT, Leweke FM, Koethe D, Gerth CW et al. Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Med 2006; 3: e327.
9. Killackey E, Yung AR. Effectiveness of early intervention in psychosis. Curr Opin Psychiatry 2007; 20: 121-125. (Pubitemid 46215417)
10. Kawanishi Y, Tachikawa H, Suzuki T. Pharmacogenomics and schizophrenia. Eur J Pharmacol 2000; 410: 227-241. (Pubitemid 32008146)
11. Lakhan SE, Kramer A. Schizophrenia genomics and proteomics: are we any closer to biomarker discovery? Behav Brain Funct 2009; 5: 2.
12. Schwarz E, Bahn S. Biomarker discovery in psychiatric disorders. Electrophoresis 2008; 29: 2884-2890. (Pubitemid 352006122)
13. Schwarz E, Bahn S. The utility of biomarker discovery approaches for the detection of disease mechanisms in psychiatric disorders. Br J Pharmacol 2008; 153(Suppl 1): S133-S136. (Pubitemid 351341011)
14. Harrison PJ, Owen MJ. Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 2003; 361: 417-419. (Pubitemid 36164980)
15. Altar CA, Jurata LW, Charles V, Lemire A, Liu P, Bukhman Y et al. Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry 2005; 58: 85-96. (Pubitemid 41008124)
16. Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with Schizophrenia. J Neurosci Res 2004; 77: 858-866. (Pubitemid 39187068)
17. Bowden NA, Scott RJ, Tooney PA. Altered gene expression in the superior temporal gyrus in Schizophrenia. BMC Genom 2008; 9: 199.
18. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic Schizophrenia. Proc Natl Acad Sci USA 2001; 98: 4746-4751. (Pubitemid 32295047)
19. Mirnics K, Middleton FA, Marquez A, Lewis DA, Levitt P. Molecular characterization of Schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000; 28: 53-67.
20. Vawter MP, Barrett T, Cheadle C, Sokolov BP, Wood III WH, Donovan DM et al. Application of cDNA microarrays to examine gene expression differences in Schizophrenia. Brain Res Bull 2001; 55: 641-650. (Pubitemid 32888383)
21. Vawter MP, Crook JM, Hyde TM, Kleinman JE, Weinberger DR, Becker KG et al. Microarray analysis of gene expression in the prefrontal cortex in Schizophrenia: a preliminary study. Schizophr Res 2002; 58: 11-20. (Pubitemid 35287279)
22. Weidenhofer J, Bowden NA, Scott RJ, Tooney PA. Altered gene expression in the amygdala in Schizophrenia: up-regulation of genes located in the cytomatrix active zone. Mol Cell Neurosci 2006; 31: 243-250. (Pubitemid 43214534)
23. Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ. Schizophrenia is associated with an increase in cortical micro-RNA biogenesis. Mol Psychiatry 2009; 15: 1176-1189.
24. Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ et al. Dysregulation of miRNA 181b in the temporal cortex in Schizophrenia. Hum Mol Genet 2008; 17: 1156-1168. (Pubitemid 351494187)
25. Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP et al. The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science (New York, NY) 2005; 310: 1817-1821. (Pubitemid 41814382)
26. Fiore R, Siegel G, Schratt G. MicroRNA function in neuronal development, plasticity and disease. Biochim Biophys Acta 2008; 1779: 471-478.
27. Krichevsky AM, Sonntag KC, Isacson O, Kosik KS. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem cells (Dayton, OH) 2006; 24: 857-864. (Pubitemid 44464719)
28. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M et al. A brain-specific microRNA regulates dendritic spine development. Nature 2006; 439: 283-289. (Pubitemid 43128846)
29. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 2004; 5: R13.
30. Mraz M, Malinova K, Mayer J, Pospisilova S. MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun 2009; 390: 1-4.
31. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19: 92-105.
32. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One 2009; 4: e6229.
33. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834-838. (Pubitemid 40839735)
34. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 2004; 101: 11755-11760. (Pubitemid 39095368)
35. Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007; 8: R214.
36. Shi M, Guo N. MicroRNA expression and its implications for the diagnosis and therapeutic strategies of breast cancer. Cancer Treat Rev 2009; 35: 328-334.
37. Iorio MV, Casalini P, Tagliabue E, Menard S, Croce CM. MicroRNA profiling as a tool to understand prognosis, therapy response and resistance in breast cancer. Eur J Cancer 2008; 44: 2753-2759.
38. Cox MB, Cairns MJ, Gandhi KS, Carroll AP, Moscovis S, Stewart GJ et al. MicroRNAs MIR-17 and MIR-20A inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 2010; 5: e12132.
39. Schipper HM, Maes OC, Chertkow HM, Wang E. MicroRNA expression in Alzheimer blood mononuclear cells. Gene Regul Syst Biol 2007; 1: 263-274.
40. Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B et al. Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimer's Dis 2008; 14: 27-41. (Pubitemid 352039013)
41. Brown AS, Derkits EJ. Prenatal infection and Schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 2010; 167: 261-280.
42. Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S et al. Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res 2008; 99: 56-70.
43. Strous RD, Shoenfeld Y. Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. J Autoimmun 2006; 27: 71-80. (Pubitemid 44528264)
44. Yolken RH, Torrey EF. Viruses, Schizophrenia, and bipolar disorder. Clin Microbiol Rev 1995; 8: 131-145.
45. Castle DJ, Jablensky A, McGrath JJ, Carr V, Morgan V, Waterreus A et al. The diagnostic interview for psychoses (DIP): development, reliability and applications. Psychol Med 2006; 36: 69-80. (Pubitemid 41825347)
46. Loughland C, Draganic D, McCabe K, Richards J, Nasir A, Allen J et al. The Australian Schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of Schizophrenia. Aust N Z J Psychiatry 2010; 44: 1029-1035.
47. 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: 180-187.
48. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98: 5116-5121. (Pubitemid 32397092)
49. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 1998; 95: 14863-14868. (Pubitemid 29003722)
50. Saldanha AJ. Java Treeview-extensible visualization of microarray data. Bioinformatics (Oxford, England) 2004; 20: 3246-3248. (Pubitemid 39619217)
51. Enright JB, Aravin AJ, Tuschl T, Sander C, Marks DS. Human microRNA targets. PLoS Biol 2004; 2: e363.
52. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15-20. (Pubitemid 40094598)
53. Hon LS, Zhang Z. The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biol 2007; 8: R166.
54. Zhang B, Kirov S, Snoddy J. WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res 2005; 33: W741-W748. (Pubitemid 44530021)
55. Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 2010; 5: e13984.
56. Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell SW, Kim TK et al. Mef2-mediated transcription of the MIR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J 2009; 28: 697-710.
57. Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J. A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 2004; 14: 1741-1748. (Pubitemid 39276432)
58. Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA et al. microRNA expression in the prefrontal cortex of individuals with Schizophrenia and schizoaffective disorder. Genome Biol 2007; 8: R27.
59. Khudayberdiev S, Fiore R, Schratt G. MicroRNA as modulators of neuronal responses. Commun Integr Biol 2009; 2: 411-413.
60. Meerson A, Cacheaux L, Goosens KA, Sapolsky RM, Soreq H, Kaufer D. Changes in brain MicroRNAs contribute to cholinergic stress reactions. J Mol Neurosci 2010; 40: 47-55.
61. Cavaille J. MicroRNAs: biosynthesis: mechanisms of action and biological functions. Ann Pathol 2007; 27: 1S31-1S32. (Pubitemid 350304207)
62. Cavaille J, Seitz H, Paulsen M, Ferguson-Smith AC, Bachellerie JP. Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. Hum Mol Genet 2002; 11: 1527-1538. (Pubitemid 34679253)
63. Kircher M, Bock C, Paulsen M. Structural conservation versus functional divergence of maternally expressed MicroRNAs in the Dlk1/Gtl2 imprinting region. BMC Genom 2008; 9: 346.
64. Royo H, Cavaille J. Non-coding RNAs in imprinted gene clusters. Biology of the Cell/Under the Auspices of the Eur Cell Biology Organization 2008; 100: 149-166. (Pubitemid 351372674)
65. Seitz H, Youngson N, Lin SP, Dalbert S, Paulsen M, Bachellerie JP et al. Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nat Genet 2003; 34: 261-262. (Pubitemid 36792855)
66. Riveros C,Mellor D, Gandhi KS, McKay FC, Cox MB, Berretta R et al. A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. PLoS One 2010; 5: e14176.
67. Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R et al. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet 2008; 40: 751-760. (Pubitemid 351748862)
68. Schaefer A, Im HI, Veno MT, Fowler CD, Min A, Intrator A et al. Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction. J Exp Med 2010; 207: 1843-1851.
69. Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell 2007; 131: 1097-1108. (Pubitemid 350235019)
70. Frank F, Sonenberg N, Nagar B. Structural basis for 50-nucleotide base-specific recognition of guide RNA by human AGO2. Nature 2010; 465: 818-822.
71. O'Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, Enright AJ et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 2007; 21: 1999-2004. (Pubitemid 47267286)
72. Lam BY, Chawla S. MEF2D expression increases during neuronal differentiation of neural progenitor cells and correlates with neurite length. Neurosci Lett 2007; 427: 153-158. (Pubitemid 47633796)
73. Linseman DA, Bartley CM, Le SS, Laessig TA, Bouchard RJ, Meintzer MK et al. Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca(2+)//calmodulin-dependent kinase II promotes depolarizationmediated cerebellar granule neuron survival. J Biol Chem 2003; 278: 41472-41481. (Pubitemid 37280976)
74. Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME. Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science (New York, NY) 1999; 286: 785-790.
75. Mao Z, Wiedmann M. Calcineurin enhances MEF2 DNA binding activity in calcium-dependent survival of cerebellar granule neurons. J Biol Chem 1999; 274: 31102-31107.
76. Okamoto S, Krainc D, Sherman K, Lipton SA. Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation. Proc Natl Acad Sci USA 2000; 97: 7561-7566. (Pubitemid 30431503)
77. Beveridge NJ, Tooney PA, Carroll AP, Tran N, Cairns MJ. Downregulation of MIR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal 2009; 21: 1837-1845.
78. Wheeler G, Ntounia-Fousara S, Granda B, Rathjen T, Dalmay T. Identification of new central nervous system specific mouse microRNAs. FEBS Lett 2006; 580: 2195-2200.
79. Glazov EA, McWilliam S, Barris WC, Dalrymple BP. Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol Biol Evol 2008; 25: 939-948.
80. Liu L, Luo GZ, Yang W, Zhao X, Zheng Q, Lv Z et al. Activation of the imprinted DLK1-DIO3 region correlates with pluripotency levels of mouse stem cells. J Biol Chem 2010; 285: 19483-19490.
81. Kagami M, O'Sullivan MJ, Green AJ, Watabe Y, Arisaka O, Masawa N et al. The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. PLoS Genet 2010; 6: e1000992.
82. Bunzel R, Blumcke I, Cichon S, Normann S, Schramm J, Propping P et al. Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain. Brain Res 1998; 59: 90-92. (Pubitemid 28408451)
83. Pun FW, Zhao C, Lo WS, Ng SK, Tsang SY, Nimgaonkar V et al. Imprinting in the Schizophrenia candidate gene GABRB2 encoding GABA(A) receptor beta(2) subunit. Mol Psychiatry 2010; 16: 557-568.
84. Cichon S, Schumacher J, Muller DJ, Hurter M, Windemuth C, Strauch K et al. A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q. Hum Mol Genet 2001; 10: 2933-2944. (Pubitemid 34030924)
85. Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger Jr JI et al. Genome scan meta-analysis of Schizophrenia and bipolar disorder, part III: bipolar disorder. Am J Hum Genet 2003; 73: 49-62. (Pubitemid 36793779)
86. Middeldorp CM, Hottenga JJ, Slagboom PE, Sullivan PF, de Geus EJ, Posthuma D et al. Linkage on chromosome 14 in a genomewide linkage study of a broad anxiety phenotype. Mol Psychiatry 2008; 13: 84-89. (Pubitemid 350275184)
87. Buiting K. Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C 2010; 154C: 365-376.
88. de los Santos T, Schweizer J, Rees CA, Francke U. Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from PWCR1, a novel imprinted gene in the Prader-Willi deletion region, which is highly expressed in brain. Am J Hum Genet 2000; 67: 1067-1082.
89. Johnstone KA, DuBose AJ, Futtner CR, Elmore MD, Brannan CI, Resnick JL. A human imprinting centre demonstrates conserved acquisition but diverged maintenance of imprinting in a mouse model for Angelman syndrome imprinting defects. Hum Mol Genet 2006; 15: 393-404. (Pubitemid 43159892)
90. Leung KN, Vallero RO, DuBose AJ, Resnick JL, LaSalle JM. Imprinting regulates mammalian snoRNA-encoding chromatin decondensation and neuronal nucleolar size. Hum Mol Genet 2009; 18: 4227-4238.
91. Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet 2000; 97: 136-146.
92. Veltman MW, Craig EE, Bolton PF. Autism spectrum disorders in Prader-Willi and Angelman syndromes: a systematic review. Psychiatric Genet 2005; 15: 243-254. (Pubitemid 44491462)
93. Whittington J, Holland A, Webb T, Butler J, Clarke D, Boer H. Cognitive abilities and genotype in a population-based sample of people with Prader-Willi syndrome. J Intellect Disabil Res 2004; 48: 172-187. (Pubitemid 38219595)
94. Holland AJ, Whittington JE, Butler J, Webb T, Boer H, Clarke D. Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader-Willi syndrome. Psychol Med 2003; 33: 141-153. (Pubitemid 36113409)
95. Jauregi J, Arias C, Vegas O, Alen F, Martinez S, Copet P et al. A neuropsychological assessment of frontal cognitive functions in Prader-Willi syndrome. J Intellect Disabil Res 2007; 51: 350-365. (Pubitemid 46502069)
96. Relkovic D, Doe CM, Humby T, Johnstone KA, Resnick JL, Holland AJ et al. Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome. Eur J Neurosci 2010; 31: 156-164.
97. Soni S, Whittington J, Holland AJ, Webb T, Maina EN, Boer H et al. The phenomenology and diagnosis of psychiatric illness in people with Prader-Willi syndrome. Psychol Med 2008; 38: 1505-1514.
98. Zollino M, Seminara L, Orteschi D, Gobbi G, Giovannini S, Della Giustina E et al. The ring 14 syndrome: clinical and molecular definition. Am J Med Genet A 2009; 149A: 1116-1124.
99. Kirov G, Grozeva D, Norton N, Ivanov D, Mantripragada KK, Holmans P et al. Support for the involvement of large copy number variants in the pathogenesis of Schizophrenia. Hum Mol Genet 2009; 18: 1497-1503.
100. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S et al. Large recurrent microdeletions associated with Schizophrenia. Nature 2008; 455: 232-236.
101. Moon HJ, Yim SV, Lee WK, Jeon YW, Kim YH, Ko YJ et al. Identification of DNA copy-number aberrations by arraycomparative genomic hybridization in patients with Schizophrenia. Biochem Biophys Res Commun 2006; 344: 531-539.
102. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. Strong association of de novo copy number mutations with sporadic Schizophrenia. Nat Genet 2008; 40: 880-885. (Pubitemid 351913650)
103. Hagan JP, O'Neill BL, Stewart CL, Kozlov SV, Croce CM. At least ten genes define the imprinted DLK1-DIO3 cluster on mouse chromosome 12qF1. PLoS One 2009; 4: e4352.