Comparative Genomic Driven Functional Studies
A major area of investigation is the use of whole genome comparative sequence analysis to identify evolutionarily conserved sequences that are enriched for gene regulatory function (http://enhancer.lbl.gov). Initial studies have focused on human sequences conserved in fish and extreme versions of those conserved in rodents. Through experimental studies in transgenic mice reporter assays, we have observed that a high percent (~50%) act as gene enhancers in vivo.
Based on these findings, we are interested in systematically testing all human-fish and other extreme categories of conserved noncoding sequences in the human genome for gene enhancer activity in transgenic mice. These data will better annotate the greater than 98% of the human genome which is noncoding and will ultimately provide insights into the rules that govern gene expression. Furthermore, these data will provide the identity to numerous enhancers which can be used to drive tissue- and cell-type specific expression in vivo, as well as provide the substrates for mutation detection in human gene regulatory elements.
