With the completion of the draft human genome sequence earlier this year, it is now possible to carry out large scale, nearly comprehensive analyses of human sequence data. One such study is to determine the sequence elements that regulate gene expression. Although the number of publicly available mRNA sequences has been increasing rapidly, the sequence databases have contained only limited data on the sequence of promoter regions that control gene expression. Now that the genome sequence has been assembled, and the genomic position of most known genes has been annotated, the sequences of candidate promoters can be easily extracted from the public data. We are developing informatics methodologies to predict which sequence elements within these promoters are involved in gene regulation. We begin with data from large-scale microarray experiments, which tell us the genes that are co-transcribed under a specific condition, and then search computationally for both known and novel transcription factor binding sites in the promoters of those genes. Our current work on a set of genes that are co-expressed across a set of melanoma-derived cell lines that differ in stages of differentiation should help to elucidate the transcriptional hierarchy involved in melanocyte development and melanoma progression. Another use for the draft human genome sequence is to catalog all members of a gene family, and to identify the orthologous relationships between these genes and genes in other completely sequenced organisms, such as Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. The ADAMs are a family of cell surface proteins that contain A Disintegrin And Metalloprotease domain. The 31 known members have been cloned from a variety of organisms, including Caenorhabditis elegans, Drosophila melanogaster, human, and other mammals. The proteins are unique in that they can display both a cell adhesion domain (an integrin-binding disintegrin domain) and a metalloprotease domain to the cell exterior. ADAMs have been implicated in a number of developmental events, such as fertilization, neurogenesis, and myogenesis, as well as several disease states, including rheumatoid arthritis, Alzheimer?s disease, and several cancers. We are developing a comprehensive catalog of all the ADAM and ADAM-like genes and pseudogenes in all fully sequenced eukaryotic genomes. This work will allow a more thorough understanding of the function of some ADAM genes, and the evolutionary events that gave rise to this large gene family. Identification of orthologous ADAMs between species will help researchers to carry out experiments in model organisms and apply those results to humans.
