Elsevier

Genomics

Volume 82, Issue 2, August 2003, Pages 162-171
Genomics

Regular article
Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia

https://doi.org/10.1016/S0888-7543(03)00101-0Get rights and content

Abstract

Schizophrenia is a common neuropsychiatric disorder of uncertain etiology that is believed to result from the interaction of environmental factors and multiple genes. To identify new genes predisposing to schizophrenia, numerous groups have focused on CAG-repeat-containing genes. We previously reported a CAG repeat polymorphism that was shown to be associated with both the severity of the phenotype and the response to medication in schizophrenic patients. In this article, we now report the genomic structure of this gene, the retinoic acid inducible-1 gene (RAI1), and present its characterization. This gene, located on chromosome 17p11.2, comprises six exons coding for a 7.6-kb mRNA. The RAI1 gene is highly homologous to its mouse counterpart and it is expressed at high levels mainly in neuronal tissues.

Section snippets

Cloning of the human RAI1 gene

Considering our demonstration of an association between the length of the CAG repeat of STS GCT10D04 and the severity and medication response in schizophrenia [5], we decided to investigate this involvement from a functional perspective. As an initial effort we isolated large genomic fragments overlapping this STS by screening the RPCI human PAC library [14] using PCR primers SCZ15 and SCZ16 designed from this STS (see Materials and Methods). We isolated one clone, hRPCI_253_P_07, which was

Conclusion

The work presented here represents the characterization of the human RAI1 gene. Our results show that this gene is very similar to its mouse ortholog both in DNA and protein sequences and in expression patterns. If we take into consideration that a polyglutamine polymorphism of RAI1 is associated with schizophrenia and that it is highly expressed in neuronal brain regions, we can hypothesize that it might be an important modulator of susceptibility to schizophrenia by modulating some aspects of

Isolation of PAC clones

The Roswell Park Cancer Institute human PAC library was screened by PCR using oligonucleotides SCZ15 and SCZ16 (Table 2) flanking the CAG repeat of STS CHLC.GCT10D04 (referred to hereafter as GCT10D04, Accession No. G09710). PCRs were carried out in a 20-μl total volume containing 20 ng of DNA, 100 ng of each oligonucleotide, 1.5 mM MgCl2, 50 mM KCl, 10 mM Tris–HCl, pH 8.3, 200 μM dNTP, 5% DMSO, and 1 U of AmpliTaq DNA polymerase (Perkin–Elmer Cetus).

PAC subcloning and sequencing

PAC DNA was digested with BamHI, EcoRI, or

Acknowledgements

The authors thank Dr. W. Edward C. Bradley for providing mRNA and Dr. Rima Slim, Dr. Patrick Dion, and Ms. Inge Meijer for their critical review of the manuscript. André Toulouse is the recipient of a postdoctoral fellowship from the Fonds de Recherche en Santé du Québec. Guy A. Rouleau holds the Graham Boeckh Chair in Schizophrenia. This work was supported by grants from the Canadian Genetic Disease Network, the Canadian Institutes of Health Research, and RGS Genome, Inc.

References (19)

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