The role of copy number variation in schizophrenia

Expert Review of Neurotherapeutics

Volumn 10, Issue 1, 2010, Pages 25-32

  Kirov, George ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

15q11.2; 15q13.3; 16p11.2; 16p13.1; 1q21.1; 22q11.2; CNV; Deletion; Duplication; Schizophrenia

Indexed keywords

CHROMOSOME 15Q; CHROMOSOME 16P; CHROMOSOME 1Q; CHROMOSOME 22Q; CHROMOSOME DELETION; COPY NUMBER VARIATION; GENE DUPLICATION; GENE LOCUS; GENETIC RISK; HEREDITY; HUMAN; MOLECULAR GENETICS; NONHUMAN; REVIEW; SCHIZOPHRENIA;

CHROMOSOMES, HUMAN; CHROMOSOMES, HUMAN, PAIR 22; DNA COPY NUMBER VARIATIONS; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; HUMANS; SCHIZOPHRENIA;

EID: 74949088599     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.09.133     Document Type: Review

References (50)

1. Solinas-Toldo S, Lampel S, Stilgenbauer S et al. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20, 399-407 (1997).
2. Pinkel D, Segraves R, Sudar D et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat. Genet. 20, 207-211 (1998).
3. Redon R, Ishikawa S, Fitch KR et al. Global variation in copy number in the human genome. Nature 444, 444-454 (2006).
4. Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. A high-resolution survey of deletion polymorphism in the human genome. Nat. Genet. 38, 75-81 (2006).
5. McCarroll SA, Kuruvilla FG, Korn JM. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40(10), 1166-1174 (2008).
6. Henrichsen CN, Chaignat E, Reymond A. copy number variants, diseases and gene expression. Hum. Mol. Genet. 18(R1), R1-R8 (2009).
7. Lee JA, Lupski JR. Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders. Neuron 52, 103-121 (2006).
8. Gottesman II. Schizophrenia genesis: the origins of madness. Henry Holt & Company Inc. New York, NY, USA (1991).
9. Kirov G, Gumus D, Chen W et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum. Mol. Genet. 17, 458-465 (2008).
10. Walsh T, McClellan JM, McCarthy SE et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539-543 (2008).
11. 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. 40, 880-885 (2008).
12. International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237-241 (2008). •• One of the largest studies on CNVs in schizophrenia. It identified the role of the 1q21.1 and 15q13.3 deletions.
13. Stefansson H, Rujescu D, Cichon S et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232-236 (2008). •• One of the largest studies on CNVs in schizophrenia. It identified the role of the 1q21.1, 15q11.2 and 15q13.3 deletions.
14. Kirov G, Grozeva D, Norton N et al. Support for the involvement of large CNVs in the pathogenesis of schizophrenia. Hum. Mol. Genet. 18(8), 1497-503 (2009). •• Confirmed the role of deletions at 15q11.2, and very large deletions in general, and suggested a role for duplications at 16p13.1 and deletions at 17p12.
15. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).
16. Ikeda M, Aleksic B, Kirov G et al. Copy number variations (CNVs) in schizophrenia in the Japanese population. Biol. Psychiatry DOI:10.1016/j. biopsych.2009.08.034 (2009) (Epub ahead of print).
17. Need AC, Ge D, Weale ME et al. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet. 5(2), e1000373 (2009).
18. Mefford HC, Sharp AJ, Baker C et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 359, 1685-1699 (2008).
19. Brunetti-Pierri N, Berg JS, Scaglia F et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat. Genet. 40(12), 1466-1471 (2008).
20. Weiss LA, Shen Y, Korn JM et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667-675 (2008).
21. Rujescu D, Ingason A, Cichon S et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. 18(5), 988-996 (2008). •• Provides strong evidence for the involvement of NRXN1 in SCZ.
22. Kirov G, Rujescu D, Ingason D et al. Neurexin 1 (NRXN1) deletions in schizophrenia. Schizophr. Bull. 35(5), 851-854 (2009).
23. Südhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455, 903-911 (2008). • Very comprehensive review of neurexins and neuroligins.
24. Glessner JT, Wang K, Cai G et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459(7246), 569-573 (2009).
25. Marshall CR, Noor A, Vincent JB et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477-488 (2008).
26. Doornbos M, Sikkema-Raddatz B, Ruijvenkamp CA et al. Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur. J. Med. Genet. 52, 108-115 (2009).
27. Mefford HC, Cooper GM, Zerr T et al. A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease. Genome Res. 19(9), 1579-1585 (2009).
28. de Kovel CG, Trucks H, Helbig I et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain DOI: 10.1093/brain/awp262 (2009) (Epub ahead of print).
29. Sharp AJ, Mefford HC, Li K et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. 40, 322-328 (2008).
30. Helbig I, Mefford HC, Sharp AJ et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat. Genet. 41, 160-162 (2009).
31. Dibbens LM, Mullen S, Helbig I et al. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum. Mol. Genet. 18(19), 3626-3631 (2009).
32. van Bon BW, Mefford HC, Menten B et al. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J. Med. Genet. 46(8), 511-523 (2009).
33. Ben-Shachar S, Lanpher B, German JR et al. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. 46, 382-388 (2009).
34. Miller DT, Shen Y, Weiss LA et al. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J. Med. Genet. 46, 242-248 (2009).
35. Pagnamenta AT, Wing K, Akha ES et al. A 15q13.3 microdeletion segregating with autism. Eur. J. Hum. Genet. 17, 687-692 (2009).
36. Ullmann R, Turner G, Kirchhoff M et al. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Hum. Mutat. 28, 674-682 (2007).
37. Hannes FD, Sharp AJ, Mefford HC et al. Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J. Med. Genet. 46(4), 223-232 (2009).
38. Ingason A, Rujescu D, Cichon S et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol. Psychiatry DOI: 10.1038/mp.2009.101 (2009) (Epub ahead of print).
39. Grozeva D, Kirov G, Ivanov D et al. Rare copy number variants (CNVs): A point of rarity in genetic risk for bipolar disorder and schizophrenia? Arch. Gen. Psychiatry (2009) (In press).
40. McCarthy S, Makarov V, Kirov G et al. Microduplications of 16p11.2 are associated with schizophrenia. Nat. Genet. 41(11), 1223-1227 (2009).
41. Bijlsma EK, Gijsbers AC, Schuurs-Hoeijmakers JH et al. Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals. Eur. J. Med. Genet. 52, 77-87 (2009).
42. Ivanov D, Kirov G, Norton N et al. A molecular genetic study of the VCFS region in patients with early onset psychosis. Brit. J. Psychiary 183, 409-413 (2003).
43. Bassett AS, Marshall CR, Lionel AC, Chow EW, Scherer SW. Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome. Hum. Mol. Genet. 17, 4045-4053 (2008).
44. Antshel KM, Aneja A, Strunge L et al. Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion). J. Autism. Dev. Disord. 37(9), 1776-1786 (2007).
45. Vorstman JA, Morcus ME, Duijff SN et al. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J. Am. Acad. Child Adolesc. Psychiatry 45(9), 1104-1113 (2006).
46. Niklasson L, Rasmussen P, Oskarsdóttir S, Gillberg C. Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Res. Dev. Disabil. 30(4), 763-773 (2009).
47. Murphy KC, Jones LA. Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch. Gen. Psychiatry 56(10), 940-945 (1999).
48. Millar JK, Wilson-Annan JC, Anderson S et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Mol. Genet. 9, 1415-1423 (2000).
49. Itsara A, Cooper GM, Baker C et al. Population analysis of large copy number variants and hotspots of human genetic disease. Am. J. Hum. Genet. 84(2), 148-161 (2009).
50. Ehninger D, Li W, Fox K et al. Reversing neurodevelopmental disorders in adults. Neuron 60, 950-960 (2008).