DOI: 10.1073/pnas.042700699. Genetic variation at the 22q11<i>PRODH2/DGCR6</i>locus presents an unusual pattern and increases susceptibility to schizophrenia

Genetic variation at the 22q11PRODH2/DGCR6locus presents an unusual pattern and increases susceptibility to schizophrenia

10.1073/pnas.042700699

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that ≈20–30% of individuals with 22q11 microdeletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood. Analysis of the extent of these microdeletions by using polymorphic markers afforded further refinement of this locus to a region of ≈1.5 Mb. Recently, a high rate of 22q11 microdeletions was also reported for a cohort of 47 patients with Childhood Onset Schizophrenia, a rare and severe form of schizophrenia with onset by age 13. It is therefore likely that this 1.5-Mb region contains one or more genes that predispose to schizophrenia. In three independent samples, we provide evidence for a contribution of thePRODH2/DGCR6locus in 22q11-associated schizophrenia. We also uncover an unusual pattern ofPRODH2gene variation that mimics the sequence of a linked pseudogene. Several of the pseudogene-like variants we identified result in missense changes at conserved residues and may prevent synthesis of a fully functional enzyme. Our results have implications for understanding the genetic basis of the 22q11-associated psychiatric phenotypes and provide further insights into the genomic instability of this region.

Bibliography

Liu, H., Heath, S. C., Sobin, C., Roos, J. L., Galke, B. L., Blundell, M. L., Lenane, M., Robertson, B., Wijsman, E. M., Rapoport, J. L., Gogos, J. A., & Karayiorgou, M. (2002). Genetic variation at the 22q11PRODH2/DGCR6locus presents an unusual pattern and increases susceptibility to schizophrenia. Proceedings of the National Academy of Sciences, 99(6), 3717â3722.

Authors 12

Hui Liu (first)
Simon C. Heath (additional)
Christina Sobin (additional)
J. Louw Roos (additional)
Brandi L. Galke (additional)
Maude L. Blundell (additional)
Marge Lenane (additional)
Brian Robertson (additional)
Ellen M. Wijsman (additional)
Judith L. Rapoport (additional)
Joseph A. Gogos (additional)
Maria Karayiorgou (additional)

References 28 Referenced 252

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10.1097/00005053-199408000-00010
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10.1038/990031
10.1016/S0165-1781(00)00246-8
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10.1101/gr.9.5.492
A P Dempster, N M Laird, D M Rubin J R Stat Soc 39B, 1–38 (1997). (10.1111/j.2517-6161.1977.tb01600.x) / J R Stat Soc by Dempster A P (1997)
10.1159/000154096
R S Spielman, R E McGinnis, W J Ewens Am J Hum Genet 52, 506–516 (1993). / Am J Hum Genet by Spielman R S (1993)
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J M Phang, G C Yeh, C R Scriver The Metabolic and Molecular Bases of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw–Hill, New York) 1, 1125–1146 (1995). / The Metabolic and Molecular Bases of Inherited Disease by Phang J M (1995)
L Erlenmeyer-Kimling Annual Review of the Schizophrenic Syndrome, ed R Cancro (Brunner/Mazel, New York) 5, 298–333 (1978). / Annual Review of the Schizophrenic Syndrome by Erlenmeyer-Kimling L (1978)
10.1523/JNEUROSCI.19-01-00021.1999
10.1073/pnas.230445997

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	8 months, 3 weeks ago (Dec. 7, 2024, 5:31 p.m.)
Indexed	2 weeks, 6 days ago (Aug. 12, 2025, 5:55 p.m.)
Issued	23 years, 5 months ago (March 12, 2002)
Published	23 years, 5 months ago (March 12, 2002)
Published Online	23 years, 5 months ago (March 12, 2002)
Published Print	23 years, 5 months ago (March 19, 2002)

Funders 0

None

BibTeX

@article{Liu_2002, title={Genetic variation at the 22q11PRODH2/DGCR6locus presents an unusual pattern and increases susceptibility to schizophrenia}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.042700699}, DOI={10.1073/pnas.042700699}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Liu, Hui and Heath, Simon C. and Sobin, Christina and Roos, J. Louw and Galke, Brandi L. and Blundell, Maude L. and Lenane, Marge and Robertson, Brian and Wijsman, Ellen M. and Rapoport, Judith L. and Gogos, Joseph A. and Karayiorgou, Maria}, year={2002}, month=mar, pages={3717–3722} }

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