title: A high proportion of chromosome 21 promoter polymorphisms influence transcriptional activity.
abstract: We have sought to obtain an unbiased estimate of the proportion of polymorphisms in promoters of human genes that have functional effects. We carried out polymorphism discovery on a randomly selected group of 51 gene promoters mapping to human chromosome 21 and successfully analyzed the effect on transcription of 38 of the sequence variants. To achieve this, a total of 53 different haplotypes from 20 promoters were cloned into a modified pGL3 luciferase reporter gene vector and were tested for their abilities to promote transcription in HEK293t and JEG-3 cells. Up to seven (18%) of the 38 tested variants altered transcription by 1.5-fold, confirming that a surprisingly high proportion of promoter region polymorphisms are likely to be functionally important. The functional variants were distributed across the promoters of CRYAA, IFNAR1, KCNJ15, NCAM2, IGSF5, and B3GALT5. Three of the genes (NCAM2, IFNAR1, and CRYAA) have been previously associated with human phenotypes and the polymorphisms we describe here may therefore play a role in those phenotypes.
authors.affiliation: Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Buckland
authors.forename: Sharol L
authors.initials: SL
authors.lastname: Coleman
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Hoogendoorn
authors.forename: Carol
authors.initials: C
authors.lastname: Guy
authors.forename: S Kaye
authors.initials: SK
authors.lastname: Smith
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D002460:Cell Line; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D008156:Luciferases