Functional analysis of polymorphisms in the promoter regions of genes on 22q11
| Autor: | Paul Robert Buckland, Michael Conlon O'Donovan, Carol Guy, Bastiaan Hoogendoorn, Sharon Louise Coleman, S. Kaye Smith |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Chromosomes
Human Pair 22 Single-nucleotide polymorphism Biology Kidney Gene dosage Cell Line DiGeorge syndrome Gene duplication Genetics medicine Ethnicity Proline Oxidase Humans Genetic Testing Promoter Regions Genetic Gene Genetics (clinical) Glutathione Transferase Reporter gene Polymorphism Genetic Haplotype Nuclear Proteins Proteins Promoter medicine.disease Molecular biology Gene Expression Regulation Genes Haplotypes Heparin Cofactor II |
| Zdroj: | Human mutation. 24(1) |
| ISSN: | 1098-1004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text