Endocrine Abstracts

Most genetic mechanisms that are currently known to underlie developmental processes and human diseases are based on the analysis of a very small portion of the genome that encodes for protein-coding sequences. Novel sequence-based technologies, however, have recently disclosed that a major portion of the noncoding genome contains functional regulatory elements. It is thus reasonable to presume that the analysis of such elements can shed new light into developmental and cellular mechanisms, and uncover new causes of human disease. The elucidation of such defects will require knowledge of the genomic location of functional noncoding elements in disease-relevant cell types, as well as an in depth understanding of how they function. I will present data showing how transcriptional network maps and epigenomics of embryonic pancreatic cells can uncover novel cis-regulatory mechanisms of pancreas development, and will also present findings that use this knowledge to identify genetic causes of Mendelian forms of human diabetes. Further, I will discuss data indicating that non-coding genome variation can also contribute to the susceptibility for common forms of human diabetes.