positional cloning A technique for isolating and cloning a gene, for example a disease-associated gene, in the absence of any information about its product. It relies on the existence of suitable genetic markers (see marker gene), whose inheritance can be traced along with the disease in question. With reference to an existing genetic map, the markers indicate the chromosomal region that contains the disease gene. DNA probes, based on DNA marker sequences in the map region, are used to select cloned segments from a DNA library. A set of contiguous overlapping clones (contigs) is assembled by the process of chromosome walking. The DNA sequence of the region can then be determined and analysed to identify stretches that might contain the sought-for disease gene. Having established the gene's base sequence, the structure and possible function of the corresponding protein can be deduced. Many important disease genes have been identified using this approach, including those for cystic fibrosis, Huntington's disease, and Friedreich's ataxia. See also physical map.
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