THE HUMAN GENOME PROJECT - FROM MAPPING TO SEQUENCING

Until recently, the ''human genome'' programs were mainly directed tow ards the development of maps to identify disease genes. The genetic ma p comprises about 8000 highly informative second generation markers of the microsatellite type. The density of markers is now sufficient to localize a gene for a monogenic disease with a precision of 1 to 2 mil lion base pairs easily, and to define intervals which contain suscepti bility genes for multifactorial disorders. A third generation map base d on single nucleotide polymorphisms that can be genotyped using DNA c hip technology is in progress. The physical map, based on sets of over lapping yeast artificial chromosomes ordered using sequence-tagged sit es, covers over 90% of the genome. However, this physical map cannot s erve as a support for sequencing because of the numerous rearrangement s that occur in yeast artificial chromosomes. An international network of laboratories has mapped a set of more than 30000 expressed sequenc es from cDNAs using whole genome radiation hybrids that enable integra tion of genes within existing maps. The human genome program is now pr ogressively shifting to massive sequencing, although sequence ready ma ps are not available for the major part of the human genome. Similarly , our capacity to interpret the available genomic sequence remains lim ited.