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| A high proportion of polymorphisms in the promoters of brain expressed genes influences transcriptional activity |
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| Author(s): Buckland PR, Hoogendoom B, Guy CA, Coleman SL, Smith SK, Buxbaum JD, Haroutunian V, O'Donovan MC |
| Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE Volume: 1690 Issue: 3 Pages: 238-249 Published: NOV 5 2004 |
| Times Cited: 27 References: 35 |
| Abstract: There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains of schizophrenics [Y Hakak, JR. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. 98 (2001) 4746-4751.]. We found 60 variants distributed across 31 of the genes. A total of 77 haplotypes representing 28 different putative promoters were analyzed in a reporter gene assay in two. cell lines. Of a total of 54 sequence variants represented in the haplotypes, 12 (or around 22%) were functional according to a highly conservative definition. These were found in the promoters of eight genes: NPY, PCSK1, NEFL, KIAA0513, LMO4, HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. (C) 2004 Elsevier B.V. All rights reserved. |
| Document Type: Article |
| Language: English |
| Reprint Address: Buckland, PR (reprint author), Univ Wales Coll Med, Dept Med Psychol, Heath Pk, Cardiff CF14 4XN, S Glam Wales |
Addresses:
1. Univ Wales Coll Med, Dept Med Psychol, Cardiff CF14 4XN, S Glam Wales
2. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10021 USA
3. Bronx Vet Affairs Med Ctr, MIRECC, Bronx, NY 10468 USA |
| Publisher: ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS |
| Subject Category: Biochemistry & Molecular Biology; Biophysics; Cell Biology |
| IDS Number: 870LG |
| ISSN: 0925-4439 |
| DOI: 10.1016/j.bbadis.2004.06.023 |
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