ABSTRACT

Genome analysis makes it possible to clone a locus based on its phenotypic expression. The cloning of trait loci can roughly be divided into four strategies: functional cloning, candidate cloning, positional cloning and positional candidate cloning. Functional cloning implies that the cloning step is performed after the biochemical characterisation of the gene product. Candidate cloning is based on the identification of candidate genes for a given trait. The usefulness of this approach is dependent on the number of potential candidate genes. If this number is too large it may be more efficient to first map the trait locus to a chromosomal region and then ask the question whether there are any candidate genes already mapped to the same region. This strategy is called positional candidate cloning and is expected to be the major strategy in the future because of the rapid development of an almost complete human transcript map. Animal geneticists will be able to utilise this strategy by accessing the human transcript map by comparative gene mapping. Finally, in positional cloning the target gene is cloned on the basis of its map position and the function of the gene is revealed subsequently. The cloning of monogenic trait loci is a demanding undertaking but relatively straightforward when good pedigree material is available. The cloning of quantitative trait loci (QTLs) is much more problematic because the poor precision in QTL mapping and our vague ideas about the molecular nature of such loci.