Assessing the impact of genetic variation on transcriptional regulation in vitro.
Two alleles of a gene that contain polymorphic cis-regulatory regions can contribute differently to expression levels. Evolutionary changes in such cis-regulatory domains are believed to have participated in the cognitive evolution of H. sapiens as well as phenotypic diversity. There have been many studies that associate genetic variations to individual's susceptibility to behavioural and affective disorders. Cis-acting regulatory polymorphisms can effect gene expression at many levels, such as transcription, mRNA processing efficiency, pre-mRNA splicing, and mRNA stability. Trans-acting modulators (such as transcription factors) also play a major role in determining mRNA concentration of a specific allele. Several studies have demonstrated that VNTRs within various genes can support differential gene expression based on copy number and that the function of the VNTR as a transcriptional regulator can be modulated, in part, by transcription factors.A better understanding of the pathways regulating expression mediated by the VNTRs would complement clinical studies, demonstrating how these domains may be mechanistically involved in the progression of the disorder and may supply more defined targets for pharmaceutical intervention.
Ali
Fahad R
FR
Division of Physiology, School of Biomedical Sciences, University of Liverpool, Liverpool, UK.
Haddley
Kate
K
Quinn
John P
JP
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D018598:Minisatellite Repeats; D051381:Rats; D017208:Rats, Wistar