ABSTRACT
A revolution in gene discovery is currently underway. The Human Genome Project, initiated in 1990, aims to determine the complete sequence of the human genome, including the estimated 100,000 genes, by the year 2005. Functional cloning refers to identification of the gene causing a human disease based on fundamental information about the basic biochemical defect, without reference to chromosomal map position. The majority of positional cloning successes have relied on cytogenetic rearrangements. Positional cloning in the absence of one or the other of these clues is still a laborious business, but the recent growth in this subroster testifies to the progress in genetic mapping, physical mapping, and gene hunting technologies arising from the Human Genome Project. The major future challenge to positional cloning will be the elucidation of genes responsible for predisposition to common oligogenic disorders such as diabetes, asthma, hypertension, many forms of cancer, and the major mental illnesses.
