University of Oulu

Human GNAL, C18orf2, and MPPE1 genes : genomic organization of the human GNAL gene and characterization of two novel genes, C18orf2 and MPPE1, on chromosome 18p11.2, a susceptibility region for schizophrenia and bipolar disorder

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Author: Vuoristo, Jussi1,2,3
Organizations: 1University of Oulu, Collagen Research Unit
2University of Oulu, Biocenter Oulu
3University of Oulu, Faculty of Medicine, Department of Medical Biochemistry and Molecular Biology
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: 2002
Publish Date: 2002-07-05
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium L101 of the Department of Medical Biochemistry and Molecular Biology, on July 5th, 2002, at 10 a.m.
Reviewer: Professor Aarno Palotie
Docent Maija Wessman


The genomic organization and mRNA expression of the human GNAL gene on chromosome 18p11.2, a region that has been associated with bipolar disorder and schizophrenia, was determined. The GNAL gene was shown to span over 80 kb and consist of twelve exons, and its structure was very similar to adenyl cyclase stimulating G protein GSα. The start site of transcription was revealed by 5'-RACE. Two polyadenylation signals were found, and 3'-RACE assay was used to verify the functional site. The GNAL gene was expressed as approximately 6 kb transcripts in various regions of the human brain, and no alternative splicing was detected. One informative CA-dinucleotide repeat of 11 alleles and 74% heterozygosity was found in intron 5, and two single nucleotide polymorphisms in introns 3 and 10 were detected by SSCP.

During characterization of the GNAL gene, two previously unknown genes were found. A novel intronless gene C18orf2 coding for a functionally unknown protein was localized to intron 5 of the GNAL gene. By semiquatitative RT-PCR, C18orf2 mRNA was found to be moderately expressed in all tissues studied here. Another novel gene, metallophosphoesterase MPPE1, was found to reside adjacent to the 3'-end of the GNAL gene in a tail-to-tail orientation. The deduced amino acid sequence revealed a highly conserved metallophosphoesterase motif gDxH..(16-60)..GDxxdr..(13-34)..GNH[DE], which is typical for various phosphate hydrolyzing enzymes, especially serine/threonine protein phosphatases. The MPPE1 gene contained fourteen exons and spanned about 27 kb. MPPE1 was expressed as a single mRNA of 2.2 kb in various regions of the human brain but not in any other tissues. Four different alternatively spliced forms of MPPE1 were detected by RT-PCR, and each transcript was shown to partially overlap with the 3'-untranslated region of the GNAL gene.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-6767-2
ISBN Print: 951-42-6766-4
Issue: 688
Copyright information: © University of Oulu, 2002. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.