Regular articleMolecular cloning and characterization of human RAI1, a gene associated with schizophrenia
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.
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