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Functional analysis of polymorphisms in the promoter regions of genes on 22q11.
- Source :
-
Human mutation [Hum Mutat] 2004 Jul; Vol. 24 (1), pp. 35-42. - Publication Year :
- 2004
-
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.<br /> (Copyright 2004 Wiley-Liss, Inc.)
- Subjects :
- Cell Line
Ethnicity genetics
Gene Expression Regulation genetics
Gene Expression Regulation physiology
Genetic Testing methods
Glutathione Transferase genetics
Haplotypes genetics
Heparin Cofactor II genetics
Humans
Kidney cytology
Kidney embryology
Kidney metabolism
Nuclear Proteins
Polymorphism, Genetic genetics
Proline Oxidase genetics
Promoter Regions, Genetic genetics
Proteins genetics
Chromosomes, Human, Pair 22 genetics
Genes genetics
Polymorphism, Genetic physiology
Promoter Regions, Genetic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 15221787
- Full Text :
- https://doi.org/10.1002/humu.20061