Common polymorphism in a highly variable region upstream of the human lactase gene affects DNA-protein interactions

摘要: In most mammals lactase activity declines after weaning when lactose is no longer part of the diet, but in many humans persists into adult life. The difference responsible for this phenotypic polymorphism has been shown to be cis-acting gene. causal sequence not found so far, a number polymorphic sites have within and near We previously that Europeans there are two small region between 974 bp 852 upstream from start transcription, which detectable by denaturing gradient gel electrophoresis (DGGE). study, analysis individuals five other population groups same DGGE method reveals four new alleles resulting three additional nucleotide changes very region. Analysis primate species comparison with published pig shows overall highly variable human conserved pigs as well primates, it lies 1 kb control downregulation pigs. Electrophoretic mobility shift assay (EMSA) studies were carried out determine whether common variation affected protein-DNA binding several activities using technique. A novel base-pair deletion populations tested, present Europeans, caused change activity. However, C T transition at −958 dramatically reduced activity, although functional significance clear.