Coupling genomics and human genetics to delineate basic mechanisms of development

This article, based on a presentation given by the author at the third Asan-Harvard Medical International Symposium on "Genomics and Proteomics: Impact on Medicine and Health" in Seoul, Korea, July 3-4, 2001, discusses an iterative translational research approach to delineate the basic mechanism of human development. The study of humans to increase the understanding of mammalian development has critical advantages that make its limitations acceptable for certain types of studies. For instance, by looking at families affected by birth defects, researchers can gain insight into the basic mechanisms of development and how genes program organisms to assume their permanent, or adult, morphological shapes. A number of malformation syndromes have some overlapping manifestations, despite being phenotypically and, in some cases, genetically distinct. What can researchers learn from this? The author's research group clinically and genetically analyzed families affected with the Pallister-Hall syndrome. The researchers then went on to look at the McKusick-Kaufman syndrome, a disorder that is more common among the Old Order Amish of Lancaster County, Pennsylvania, in an attempt to understand more about genes, genetic pathways, and syndrome families.