The Cloning of the Gene for Hereditary Hemochromatosis

Featured Article: Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996;13: 399–408.4The early 1990s represented the beginning of modern-day human genomics. Methodologies for genetic linkage analysis of human disease genes had become well established, and a new class of polymorphic microsatellite genetic markers had recently been discovered. The ability to manipulate human genomic DNA as yeast and bacterial artificial chromosomes, coupled with these new tools, provided an unprecedented way to construct detailed physical and genetic maps. Combining these maps with emerging technologies to identify expressed sequences, as well as the introduction of high-throughput capillary-based DNA sequencing, made gene finding more tractable than ever. Collectively, the application of these methods to the isolation of human disease genes was known as “positional cloning,” and the early 1990s saw the emergence of several biotechnology companies founded to capitalize on the confluence of these technologies.One of these companies was Mercator Genetics of Menlo Park, California. The company's plan was simple: establish a positional cloning platform and “rapidly” …