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Linkage analysis and the tracking of susceptibility genes

Linkage analysis, the method by which a disease gene can be mapped to a specific locus by its association with other known loci on the same chromosome, is one of the most powerful tools in gene discovery. It enables the researcher to make sense of the complex geography of the genome and 'home in' on a particular place, first by country, then region, and finally, to continue the analogy, to a specific town. Molecular biological techniques are now so advanced that once a gene has been linked to a specific chromosomal region it is only a matter of time and time that is becoming progressively shorter as the human genome project races on before the gene itself is cloned. In that period before the gene is isolated known DNA markers at loci closely flanking the critical region in which the gene must lie can be used diagnostically to track disease chromosomes through families. In the past such markers were indispensable to the diagnostic laboratory and, whilst today their use has been largely superseded by direct mutation testing as genes are isolated, they remain indispensable as an adjunct either a) by supporting the results of mutation analysis or b) by providing a more rapid result to the patient before time consuming mutation analysis is complete.