Functional analysis of human promoter polymorphisms

Abstract

The potential importance of gene regulation in disease susceptibility and other inherited phenotypes has been underlined by the observation that the human genome contains fewer protein coding genes than expected. Promoter sequences are potential sources of polymorphism affecting gene expression, although to date there are no large-scale systematic studies that have determined how frequently such variants occur. We have used denaturing high performance liquid chromatography to screen the first 500 bp of the 5' flanking region of 170 opportunistically selected genes identified from the Eukaryotic Promoter Database (EPD) for common polymorphisms. Using a screening set of 16 chromosomes, single-nucleotide polymorphisms were found in approximately 35% of genes. It was attempted to clone each of these promoters into a T-vector constructed from the reporter gene vector pGL3. The relative ability of each promoter haplotype to promote transcription of the luciferase gene was tested in each of three human cell lines (HEK293, JEG and TE671) using a co-transfected SEAP-CMV plasmid as a control. The findings suggest that around a third of promoter variants may alter gene expression to a functionally relevant extent.

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

“…Almost one-third of promoter variants may alter gene expression and result in phenotypic variation (30). The effects of different alleles (T versus G) in the SNP rs1617640 of the EPO promoter on its expression are consistent with this notion.…”

Expression quantitative trait loci analysis of genes in porcine muscle by quantitative real-time RT-PCR compared to microarray data

“…Typically, cis-acting eQTL are considered to include SNPs that are within 100 kb upstream and downstream of the gene that is affected by that eQTL. On the basis of earlier work involving human genes with promoter polymorphisms, it has been estimated that a sizable fraction of cisvariants (about one-third of the SNPs in promoters) may alter gene expression (Hoogendoorn et al, 2003;Buckland, 2004). One study recently reported on the investigation of cis-regulatory variations in 3 0 -UTRs for a set of genes showing cis-acting regulation in a panel of mouse recombinant congenic strains (Lee et al, 2006).…”

Genetic associations with diminished ovarian reserve: a systematic review of the literature

“…Particularly, the promoter region of genes contains polymorphisms and such polymorphisms have been shown to contain a large amount of genetic variation [33]. Gene polymorphisms associated with DOR are discussed in Table 1.…”