Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-12T04:00:20.327Z Has data issue: false hasContentIssue false
  • English
  • Français

Genomic structural variation in psychiatric disorders

Published online by Cambridge University Press:  15 October 2012

James J. H. Rucker  and
Peter McGuffin
James J. H. Rucker*
Affiliation:
Kings College London
Peter McGuffin
Affiliation:
Kings College London
*
Address correspondence and reprint requests to: James Rucker, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, 16 De Crespigny Park, London SE5 8AF, UK; E-mail: james.rucker@kcl.ac.uk.
Get access Rights & Permissions [Opens in a new window]

Abstract

Copy number variants (CNVs) are submicroscopic deletions and duplications of genomic material that were previously thought to be rare phenomena. They have now been robustly associated with a variety of disorders such as autism, schizophrenia, and attention-deficit/hyperactivity disorder through an emerging research base in affective disorders. A complex picture is emerging of a polygenic, heterogeneous model of disease, with CNVs conferring broad susceptibility to a variety of neurodevelopmental disorders, rather than specific disorders per se. Although the insights gleaned thus far only represent a small piece of a much larger puzzle, progress has been rapid and new technologies promise even more insights into these hitherto opaque brain disorders. We will discuss CNVs, the current state of evidence for their role in the pathogenesis of classical psychiatric disorders, and the application of such knowledge in clinical settings.

Type
Articles
Information
Development and Psychopathology , Volume 24 , Issue 4: Contributions of the Genetic/Genomic Sciences to Developmental Psychopathology , November 2012 , pp. 1335 - 1344
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed., text revision). Arlington, VA: Author.Google Scholar
Andreasen, N. (1995). Symptoms, signs, and diagnosis of schizophrenia. Lancet, 346(8973), 477–481.Google Scholar
Babatz, T. D., Kumar, R. A., Sudi, J., Dobyns, W. B., & Christian, S. L. (2009). Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Research, 2, 359–364.Google Scholar
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., et al. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25, 63–77.Google Scholar
Ballif, B. C., Theisen, A., Coppinger, J., Gowans, G. C., Hersh, J. H., Madan-Khetarpal, S., et al. (2008). Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication. Molecular Cytogenetics, 1, 8.Google Scholar
Biederer, T., & Südhof, T. C. (2000). Mints as adaptors. Direct binding to neurexins and recruitment of munc18. Journal of Biological Chemistry, 275, 39803–39806.Google Scholar
Biederman, J. (1998). Attention-deficit/hyperactivity disorder: A life-span perspective. Journal of Clinical Psychiatry, 59(S7), 4–16.Google ScholarPubMed
Brzustowicz, L. M., Hodgkinson, K. A., Chow, E. W., Honer, W. G., & Bassett, A. S. (2000). Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science, 288(5466), 678–682.Google Scholar
Buizer-Voskamp, J. E., Muntjewerff, J.-W., Genetic Risk and Outcome in Psychosis (GROUP) Consortium Members Strengman, E., Sabatti, C., Stefansson, H., et al. (2011). Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients. Biological Psychiatry, 70, 655–662.CrossRefGoogle ScholarPubMed
Camp, N., Lowry, M., Richards, R., Plenk, A., Carter, C., Hensel, C., et al. (2005). Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders. American Journal of Medical Genetics: Part B Neuropsychiatric Genetics, 135B, 85–93.Google Scholar
Cardno, A. G., & Gottesman, I. I. (2000). Twin studies of schizophrenia: From bow-and-arrow concordances to Star Wars Mx and functional genomics. American Journal of Medical Genetics, 97, 12–17.Google Scholar
Cichon, S., Craddock, N., Daly, M., Faraone, S., Gejman, P., Kelsoe, J., et al. (2009). Genomewide association studies: history, rationale, and prospects for psychiatric disorders. American Journal of Psychiatry, 166, 540–556.Google Scholar
Cichon, S., Mühleisen, T. W., Degenhardt, F. A., Mattheisen, M., Miró, X., Strohmaier, J., et al. (2011). Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. American Journal of Medical Genetics, 88, 372–381.Google ScholarPubMed
Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., et al. (2010). Origins and functional impact of copy number variation in the human genome. Nature, 464(7289), 704–712.Google Scholar
Craddock, N., & Forty, L. (2006). Genetics of affective (mood) disorders. European Journal of Human Genetics, 14, 660–668.Google Scholar
Craddock, N., & Jones, I. (1999). Genetics of bipolar disorder. Journal of Medical Genetics, 36, 585–594.Google Scholar
Craddock, N., Hurles, M. E., Cardin, N., Pearson, R. D., Plagnol, V., Robson, S., et al. (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature, 464(7289), 713–720.Google Scholar
Degenhardt, F., Priebe, L., Herms, S., Mattheisen, M., Mühleisen, T. W., Meier, S., et al. (2012). Association between copy number variants in 16p11.2 and major depressive disorder in a German case-control sample. American Journal of Medical Genetics: Part B Neuropsychiatric Genetics, 159B, 263–273.Google Scholar
Dulubova, I., Khvotchev, M., Liu, S., Huryeva, I., Südhof, T. C., & Rizo, J. (2007). Munc18-1 binds directly to the neuronal SNARE complex. Proceedings of the National Academy of Sciences, 104, 2697–2702.Google Scholar
Elia, J., Gai, X., Xie, H. M., Perin, J. C., Geiger, E., Glessner, J. T., et al. (2010). Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Molecular Psychiatry, 15, 637–646.Google Scholar
Falconer, D. (1965). The inheritance of liability to certain diseases, estimated from the incidence among relatives. Annals of Human Genetics, 29 51–76.Google Scholar
Feng, J., Schroer, R., Yan, J., Song, W., Yang, C., Bockholt, A., et al. (2006). High frequency of neurexin 1β signal peptide structural variants in patients with autism. Neuroscience Letters, 409, 10–13.Google Scholar
Feuk, L., Carson, A., & Scherer, S. (2006). Structural variation in the human genome. Nature Reviews Genetics, 7, 85–97.Google Scholar
Franke, B., Neale, B. M., & Faraone, S. V. (2009). Genome-wide association studies in ADHD. Human Genetics, 126, 13–50.Google Scholar
Freeman, J. L., Perry, G. H., Feuk, L., Redon, R., McCarroll, S. A., Altshuler, D. M., et al. (2006). Copy number variation: new insights in genome diversity. Genome Research, 16, 949–961.Google Scholar
Friedman, J. M., Baross, A., Delaney, A. D., Ally, A., Arbour, L., Asano, J., et al. (2006). Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. American Journal of Medical Genetics, 79, 500–513.Google Scholar
Glessner, J., Wang, K., Sleiman, P., Zhang, H., Kim, C., Flory, J., et al. (2010). Duplication of the SLIT3 locus on 5q35.1 predisposes to major depressive disorder. PLoS One, 5, e15463.Google Scholar
Gottesman, I. I. (1991). Schizophrenia genesis: The origins of madness. New York: W. H. Freeman.Google Scholar
Gottesman, I., & Shields, J. (1967). A polygenic theory of schizophrenia. Proceedings of the National Academy of Sciences, 58, 199–205.Google Scholar
Grozeva, D., Kirov, G., Ivanov, D., Jones, I., Jones, L., Green, E., et al. (2010). Rare copy number variants: A point of rarity in genetic risk for bipolar disorder and schizophrenia. Archives of General Psychiatry, 67, 318–327.Google Scholar
Guilmatre, A., Dubourg, C., Mosca, A. L., Legallic, S., Goldenberg, A., Drouin-Garraud, V., et al. (2009). Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Archives of General Psychiatry, 66, 947–956.Google Scholar
Harris, E., & Barraclough, B. (1998). Excess mortality of mental disorder. British Journal of Psychiatry, 173 11–53.Google Scholar
Holmans, P., Zubenko, G., Crowe, R., Depaulo, J. J., Scheftner, W., Weissman, M., et al. (2004). Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q. American Journal of Medical Genetics, 74, 1154–1167.Google Scholar
Iafrate, A., Feuk, L., Rivera, M., Listewnik, M., Donahoe, P., Qi, Y., et al. (2004). Detection of large-scale variation in the human genome. Nature Genetics, 36, 949–951.Google Scholar
Ingason, A., Rujescu, D., Cichon, S., Sigurdsson, E., Sigmundsson, T., Pietilainen, O. P. H., et al. (2011). Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Molecular Psychiatry, 16, 17–25.Google Scholar
International Schizophrenia Consortium. (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature, 455(7210), 237–241.Google Scholar
Judd, L. L., & Schettler, P. J. (2010). The long term course and clinical management of bipolar I and bipolar II disorders. In Yatham, L. N. & Maj, M. (Eds.), Bipolar disorder: Clinical and neurobiological foundations. Hoboken, NJ: Wiley.Google Scholar
Karayiorgou, M., Simon, T. J., & Gogos, J. A. (2010). 22q11.2 microdeletions: Linking DNA structural variation to brain dysfunction and schizophrenia. Nature Reviews Neuroscience, 11, 402–416.Google Scholar
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C., & Eaves, L. J. (1992). A population-based twin study of major depression in women: The impact of varying definitions of illness. Archives of General Psychiatry, 49, 257–266.CrossRefGoogle ScholarPubMed
Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the National Comorbidity Survey. Archives of General Psychiatry, 51, 8.Google Scholar
Kim, H.-G., Kishikawa, S., Higgins, A. W., Seong, I.-S., Donovan, D. J., Shen, Y., et al. (2008). Disruption of neurexin 1 associated with autism spectrum disorder. American Journal of Medical Genetics, 82, 199–207.Google Scholar
Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K., Holmans, P., et al. (2009). Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Human Molecular Genetics, 18, 1497–1503.Google Scholar
Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., et al. (2007). Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Human Molecular Genetics, 17, 458–465.Google Scholar
Kirov, G., Rujescu, D., Ingason, A., Collier, D. A., O'Donovan, M. C., & Owen, M. J. (2009). Neurexin 1 (NRXN1) deletions in schizophrenia. Schizophrenia Bulletin, 35, 851–854.Google Scholar
Lander, E., Linton, L., Birren, B., Nusbaum, C., Zody, M., Baldwin, J., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860–921.Google Scholar
Lesch, K.-P., Selch, S., Renner, T. J., Jacob, C., Nguyen, T. T., Hahn, T., et al. (2011). Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: Association with neuropeptide Y gene dosage in an extended pedigree. Molecular Psychiatry, 16, 491–503.Google Scholar
Levinson, D. F., Duan, J., Oh, S., Wang, K., Sanders, A. R., Shi, J., et al. (2011). Copy number variants in schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. American Journal of Psychiatry, 168, 302–316.Google Scholar
Lewis, C., Ng, M., Butler, A., Cohen-Woods, S., Uher, R., Pirlo, K., et al. (2010). Genome-wide association study of major recurrent depression in the U.K. population. American Journal of Psychiatry, 167, 949–957.Google Scholar
Locke, D., Segraves, R., Carbone, L., Archidiacono, N., Albertson, D., Pinkel, D., et al. (2003). Large-scale variation among human and great ape genomes determined by array comparative genomic hybridization. Genome Research, 13, 347–357.Google Scholar
Longman, C. (2003). Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Human Molecular Genetics, 12, 2853–2861.CrossRefGoogle ScholarPubMed
Lupski, J. (2007). An evolution revolution provides further revelation. Bioessays, 29, 1182–1184.Google Scholar
Malhotra, D., McCarthy, S., Michaelson, J. J., Vacic, V., Burdick, K. E., Yoon, S., et al. (2011). High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron, 72, 951–963.Google Scholar
Marshall, C., Noor, A., Vincent, J., Lionel, A., Feuk, L., Skaug, J., et al. (2008). Structural variation of chromosomes in autism spectrum disorder. American Journal of Medical Genetics, 82, 477–488.Google Scholar
McCarroll, S. A., Hadnott, T. N., Perry, G. H., Sabeti, P. C., Zody, M. C., Barrett, J. C., et al. (2006). Common deletion polymorphisms in the human genome. Nature Genetics, 38, 86–92.Google Scholar
McCarthy, S. E., Makarov, V., Kirov, G., Addington, A. M., McClellan, J., Yoon, S., et al. (2009). Microduplications of 16p11.2 are associated with schizophrenia. Nature Genetics, 41, 1223–1227.Google Scholar
McGuffin, P., Katz, R., Watkins, S., & Rutherford, J. (1996). A hospital-based twin register of the heritability of DSM-IV unipolar depression. Archives of General Psychiatry, 53, 129–136.Google Scholar
McGuffin, P., Knight, J., Breen, G., Brewster, S., Boyd, P. R., Craddock, N., et al. (2005). Whole genome linkage scan of recurrent depressive disorder from the depression network study. Human Molecular Genetics, 14, 3337–3345.Google Scholar
McGuffin, P., Rijsdijk, F., Andrew, M., Sham, P., Katz, R., & Cardno, A. (2003). The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry, 60, 497–502.Google Scholar
McQuillin, A., Bass, N., Anjorin, A., Lawrence, J., Kandaswamy, R., Lydall, G., et al. (2011). Analysis of genetic deletions and duplications in the University College London bipolar disorder case control sample. European Journal of Human Genetics, 19, 588–592.Google Scholar
Morrow, E. M., Yoo, S.-Y., Flavell, S. W., Kim, T.-K., Lin, Y., Hill, R. S., et al. (2008). Identifying autism loci and genes by tracing recent shared ancestry. Science, 321(5886), 218–223.Google Scholar
Muglia, P., Tozzi, F., Galwey, N. W., Francks, C., Upmanyu, R., Kong, X. Q., et al. (2010). Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts. Molecular Psychiatry, 15, 589–601.Google Scholar
Murphy, K., Jones, L., & Owen, M. (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry, 56, 940–945.CrossRefGoogle ScholarPubMed
Need, A., Ge, D., Weale, M., Maia, J., Feng, S., Heinzen, E., et al. (2009). A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genetics, 5, e1000373.Google Scholar
Perry, G. H., Ben-Dor, A., Tsalenko, A., Sampas, N., Rodriguez-Revenga, L., Tran, C. W., et al. (2008). The fine-scale and complex architecture of human copy-number variation. American Journal of Medical Genetics, 82, 685–695.Google Scholar
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 466(7304), 368–372.CrossRefGoogle ScholarPubMed
Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: A systematic review and metaregression analysis. American Journal of Psychiatry, 164, 942–948.Google Scholar
Priebe, L., Degenhardt, F. A., Herms, S., Haenisch, B., Mattheisen, M., Nieratschker, V., et al. (2011). Genome-wide survey implicates the influence of copy number variants (CNVs) in the development of early-onset bipolar disorder. Molecular Psychiatry, 1–12.Google Scholar
Rietschel, M., Mattheisen, M., Frank, J., Treutlein, J., Degenhardt, F., Breuer, R., et al. (2010). Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biological Psychiatry, 68, 578–585.Google Scholar
Risch, N., & Merikangas, K. (1996). The future of genetic studies of complex human diseases. Science, 273(5281), 1516–1517.Google Scholar
Robin, N., & Shprintzen, R. (2005). Defining the clinical spectrum of deletion 22q11.2. Journal of Pediatrics, 147, 90–96.CrossRefGoogle ScholarPubMed
Rucker, J. J. H., Breen, G., Pinto, D., Pedroso, I., Lewis, C. M., Cohen-Woods, S., et al. (2011). Genome-wide association analysis of copy number variation in recurrent depressive disorder. Molecular Psychiatry. Advance online publication. doi:10.1038/mp.2011.144Google Scholar
Rujescu, D., Ingason, A., Cichon, S., Pietiläinen, O. P. H., Barnes, M. R., Toulopoulou, T., et al. (2009). Disruption of the neurexin 1 gene is associated with schizophrenia. Human Molecular Genetics, 18, 988–996.Google Scholar
Schena, M., Shalon, D., Davis, R., & Brown, P. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science, 270(5235), 467–470.Google Scholar
Schulze, T. G., Detera-Wadleigh, S. D., Akula, N., Gupta, A., Kassem, L., Steele, J., et al. (2009). Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Molecular Psychiatry, 14, 487–491.Google Scholar
Schwab, S. G., & Wildenauer, D. B. (2009). Update on key previously proposed candidate genes for schizophrenia. Current Opinion in Psychiatry, 22, 147–153.Google Scholar
Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., et al. (2004). Large-scale copy number polymorphism in the human genome. Science, 305(5683), 525–528.Google Scholar
Sharp, A., Mefford, H., Li, K., Baker, C., Skinner, C., Stevenson, R., et al. (2008). A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nature Genetics, 40, 322–328.Google Scholar
Shi, J., Potash, J. B., Knowles, J. A., Weissman, M. M., Coryell, W., Scheftner, W. A., et al. (2011). Genome-wide association study of recurrent early-onset major depressive disorder. Molecular Psychiatry, 16, 193–201.Google Scholar
Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., et al. (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics, 43, 977–983.Google Scholar
Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O., Ingason, A., Steinberg, S., et al. (2008). Large recurrent microdeletions associated with schizophrenia. Nature, 455(7210), 232–236.Google Scholar
Sudhof, T. (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455(7215), 903–911.Google Scholar
Sullivan, P. F. (2005). The genetics of schizophrenia. PLoS Medicine, 2, e212.Google Scholar
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry, 157, 1552–1562.Google Scholar
Sullivan, P., Kendler, K., & Neale, M. (2003). Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies. Archives of General Psychiatry, 60, 1187–1192.Google Scholar
Szatmari, P., Paterson, A., Zwaigenbaum, L., Roberts, W., Brian, J., Liu, X., et al. (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genetics, 39, 319–328.Google Scholar
Terracciano, A., Sanna, S., Uda, M., Deiana, B., Usala, G., Busonero, F., et al. (2010). Genome-wide association scan for five major dimensions of personality. Molecular Psychiatry, 15, 647–656.Google Scholar
Uher, R. (2009). The role of genetic variation in the causation of mental illness: An evolution-informed framework. Molecular Psychiatry, 14 1072–1082.Google Scholar
Vassos, E., Collier, D. A., Holden, S., Patch, C., Rujescu, D., St Clair, D., et al. (2010). Penetrance for copy number variants associated with schizophrenia. Human Molecular Genetics, 19, 3477–3481.Google Scholar
Vrijenhoek, T., Buizervoskamp, J., Vanderstelt, I., Strengman, E., Sabatti, C., Geurstvankessel, A., et al. (2008). Recurrent CNVs disrupt three candidate genes in schizophrenia patients. American Journal of Medical Genetics, 83, 504–510.Google Scholar
Walsh, T., McClellan, J., McCarthy, S., Addington, A., Pierce, S., Cooper, G., et al. (2008). Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science, 320(5875), 539–543.Google Scholar
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. New England Journal of Medicine, 358, 667–675.Google Scholar
Weissman, M. M., Leaf, P. J., Tischler, G. L., Blazer, D. G., Karno, M., Bruce, M. L., et al. (1988). Affective disorders in five United States communities. Psychological Medicine, 18, 141–153.Google Scholar
Williams, N. M., Zaharieva, I., Martin, A., Langley, K., Mantripragada, K., Fossdal, R., et al. (2010). Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: A genome-wide analysis. Lancet, 376(9750), 1401–1408.Google Scholar
World Health Organisation. (1992). The ICD-10 for Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines. Geneva: Author.Google Scholar
World Health Organisation. (n.d.). Depression. Retrieved November 8, 2011, from http://www.who.int/mental_health/management/depression/definition/en/Google Scholar
Wray, N. R., Pergadia, M. L., Blackwood, D. H. R., Penninx, B. W. J. H., Gordon, S. D., Nyholt, D. R., et al. (2012). Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned. Molecular Psychiatry, 17, 36–48.Google Scholar
Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008). Strong association of de novo copy number mutations with sporadic schizophrenia. Nature Genetics, 40, 880–885.Google Scholar
Zhang, D., Cheng, L., Qian, Y., Alliey-Rodriguez, N., Kelsoe, J., Greenwood, T., et al. (2009). Singleton deletions throughout the genome increase risk of bipolar disorder. Molecular Psychiatry, 14, 376–380.CrossRefGoogle ScholarPubMed
Zhang, F., Gu, W., Hurles, M., & Lupski, J. (2009). Copy number variation in human health, disease, and evolution. Annual Reviews in Genomics and Human Genetics, 10 451–481.Google Scholar
Zhang, J. (2003). Evolution by gene duplication: An update. Trends in Ecology and Evolution, 18, 292–298.Google Scholar