title: Functional implications of genetic variation in non-coding DNA for disease susceptibility and gene regulation.
abstract: The role of host genetic variation in determining susceptibility to complex disease traits is the subject of much research effort, but it often remains unclear whether disease-associated genetic polymorphisms are themselves functionally relevant or acting only as markers within an extended haplotype. Experimental approaches to investigate the functional impact of polymorphisms in non-coding regulatory DNA sequences for gene expression are discussed, including the role of gel-shift assays, DNA footprinting and reporter gene analysis. The limitations of different experimental approaches are presented together with future prospects for in vivo analysis. The strategic application of these functional approaches is discussed and illustrated by analysis of the role of genetic variation in the tumour necrosis factor promoter region in determining susceptibility to severe malaria.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford OX3 7BN, UK. julian@well.ox.ac.uk
authors.forename: Julian C
authors.initials: JC
authors.lastname: Knight
mesh_terms: D004247:DNA / Q000235:genetics*; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006801:Humans; D008288:Malaria / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004247:DNA