Gene Mapping Goes from FISH to Surfing the Net

The arrival of the second millennium will usher in unsurpassed information and knowledge of our genetic constitution, and will promise to revolutionize basic research and molecular medicine. The road toward a complete understanding of our genetic makeup is largely the fruit of the Human Genome Project that has initiated, advanced, and made major strides in constructing genetic and physical maps of humans and other model organisms. Already entire genomic sequences of a few prokaryotic organisms have become available with efforts toward completion of the budding yeast not too far behind. Gene mapping and identification are critical steps in this ambitious undertaking. Unfortunately, the identification of genes, especially those responsible for the vast majority of inherited human disorders, must often proceed without any knowledge of then biochemical functions. To wit, positional cloning (1 ) has taken center stage toward the initial steps in the molecular characterization of the estimated 100,000 genes in the human genome. This approach has garnered over 60 “diseased” genes thus far, with many more to come as the process becomes more streamlined. Despite having achieved in the last several years a framework of genetic and physical maps of the human genome, nonetheless the efficient and comprehensive isolation of transcribed sequences within large targeted genomic intervals remains a formidable task. The numerous chapters in this book document the creativity and ingenuity of various investigators and laboratories in this global effort. Our aim in this introductory chapter is to give an overview of gene mapping and assess where approaches in gene isolation are headed in the near future.