In silico approaches for investigating mechanisms of gene regulation

More than 95% of the human genome is made up of non-coding DNA, historically dismissed as ‘junk DNA’ of unknown function. It is now known that the so-called junk DNA isn’t junk at all; in fact, it contains important information specifying how genes are regulated. Non-coding DNA sequences located adjacent to genes typically contain binding sites for proteins that act like regulatory switches, turning genes on or off in the appropriate cell types and under particular conditions. Errors in this process have been linked to diseases ranging from cancer to obesity. Recent studies have determined that there are a surprisingly large number of non-coding sequences that are highly conserved across the vertebrate lineage. These regions, termed ‘ultraconserved sequences’, are almost identical in humans, rodents and fish. They have been minimally explored but appear to have an important role in regulating the expression of key developmental genes. Shannan Ho Sui is studying the properties of ultraconserved regions in the human genome to assess their potential role in gene regulation. Her research involves using bioinformatics techniques to find and analyze patterns in DNA sequences. By determining the properties of genes associated with ultraconserved regions, evaluating how frequently recombination occurs in these regions, and locating similarly highly conserved non-coding sequences in the fly and worm genomes, Shannan hopes to develop a model describing how and why these regions are maintained in the genome. Her research results will provide valuable insights into mechanisms of gene regulation that play important roles in development and disease.