Gene Assignment by Random Search in Human Genome

Abstract

Currently close to 2000 genes have been mapped to the human genome and over 500 genetic disorders have their chromosomal assignment (Human Gene Mapping Conference 1991). The speed of further assignments in years to come is predicted to increase since the tools for efficient mapping of any human disease are better than ever. Most disorders which have already been assigned to a chromosome were mapped by locating the wild-type gene. This was for the case phenylalanine hydroxylase, deficient in phenylketonuria, which was mapped to 12q actually independently of the disease. However, in the case of about 50 human mendelian diseases the clinical phenotype was mapped by family linkage studies using polymorphic anchor markers localized in individual chromosomes. Previously these markers represented protein polymorphisms, but more recently the accumulated information on human genome has revealed an enormous wealth of DNA polymorphisms and, consequently, a much more informative map of markers has emerged (Botstein et al. 1980). Table 1 provides a list of examples of mapped mendelian disorders for which the biochemical basis was not previously known and for which mapping really served as the first step towards a basic understanding of the disease (McKusick 1991).