Functional analysis of polymorphisms in the promoter regions of genes on 22q11
2004; Wiley; Volume: 24; Issue: 1 Linguagem: Inglês
10.1002/humu.20061
ISSN1098-1004
AutoresBastiaan Hoogendoorn, Sharon L. Coleman, Carol Guy, S. K. Smith, Michael O’Donovan, Paul R. Buckland,
Tópico(s)Genomic variations and chromosomal abnormalities
ResumoHuman MutationVolume 24, Issue 1 p. 35-42 Research Article Functional analysis of polymorphisms in the promoter regions of genes on 22q11†‡ Bastiaan Hoogendoorn, Bastiaan Hoogendoorn Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorSharon L. Coleman, Sharon L. Coleman Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorCarol A. Guy, Carol A. Guy Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorS. Kaye Smith, S. Kaye Smith Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorMichael C. O'Donovan, Michael C. O'Donovan Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorPaul R. Buckland, Corresponding Author Paul R. Buckland [email protected] Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKDepartment of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UKSearch for more papers by this author Bastiaan Hoogendoorn, Bastiaan Hoogendoorn Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorSharon L. Coleman, Sharon L. Coleman Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorCarol A. Guy, Carol A. Guy Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorS. Kaye Smith, S. Kaye Smith Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorMichael C. O'Donovan, Michael C. O'Donovan Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKSearch for more papers by this authorPaul R. Buckland, Corresponding Author Paul R. Buckland [email protected] Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UKDepartment of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UKSearch for more papers by this author First published: 27 May 2004 https://doi.org/10.1002/humu.20061Citations: 30 † Communicated by Michael Dean ‡ Disclaimer: The authors have no competing financial interests in the data presented. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Segmental aneusomy, which includes chromosome 22 deletion syndrome (del(22)(q11.2q11.2)), has been associated with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face (CAF) syndrome, cat-eye syndrome (CES), der(22) syndrome, and duplication of the del(22)(q11.2q11.2) syndrome's typically deleted region. Adults with del(22)(q11.2q11.2) may develop psychiatric illnesses, including schizophrenia, schizoaffective disorder, and bipolar disorder, suggesting that lower gene dosage leads to a predisposition to these illnesses. In a bid to identify important regulatory polymorphisms (SNPs) that may emulate changes in gene dosage of the genes within the common deletion, we have analyzed the promoter region of 47 genes (44 of which encode a protein with known function) encoding proteins in and around 22q11 for sequence variants. A total of 33 of the promoters contained polymorphisms. Of those, 25 were cloned into a reporter gene vector, pGL3. The relative ability of each promoter haplotype to promote transcription of the luciferase gene was tested in each of two human cell lines (HEK293t and TE671), using a cotransfected CMV-SPAP plasmid as an internal control. Five genes (PRODH, DGCR14, GSTT2, SERPIND1, and a gene tentatively called DKFZP434P211) showed activity differences between haplotypes of greater than 1.5-fold. Of those, PRODH, which encodes proline dehydrogenase, has previously been highlighted in relation to schizophrenia, and the functional promoter polymorphism reported here may be involved in pathogenic mechanisms. Hum Mutat 24:35–42, 2004. © 2004 Wiley-Liss, Inc. REFERENCES Arinami T, Ohtsuki T, Takase K, Shimizu H, Yoshikawa T, Horigome H, Nakayama J, Toru M. 2001. Screening for 22q11 deletions in a schizophrenia population. Schizophr Res 52: 167– 170. Bajic VB, Seah SH, Chong A, Krishnan SPT, Koh JLY, Brusic V. 2003. 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