Filling in the gaps: deciphering the function of noncoding DNA.

Study Hypothesis Less than 2% of human DNA codes for proteins, whereas the vast majority of DNA in the human genome consists of sequences with unknown function. A substantial portion of the noncoding sequences harbors regulatory motifs important for gene expression. Recent genome-wide association studies (GWAS) suggest that the majority of single nucleotide polymorphisms (SNPs) associated with human traits and diseases are found in noncoding genomic regions, potentially involving regulatory elements. The critical role of distal regulatory elements, that is, enhancers, is highlighted in GWAS of expression quantitative trait loci (eQTLs) showing that 70–80% of regulatory variants are found at large distances from protein-coding genes. In this report, May et al1 generated a genome-wide catalogue of enhancers from human myocardium. As it is well established that sequence variations in a noncoding regulatory sequence can lead to abnormal gene expression, mapping of the genomic coordinates of enhancers in a given tissue is the first step toward elucidating the function of these noncoding DNA sequences and gaining a better understanding of the mechanisms by which sequence variations in regulatory sequences affect human biology.