Linkage Mapping

The observations by Thomas Hunt Morgan that the amount of crossing over between linked genes differs led to the idea that crossover frequency might indicate the distance separating genes on the chromosome. Morgan's student Alfred Sturtevant developed the first genetic map, also called a linkage map.

Sturtevant proposed that the greater the distance between linked genes, the greater the chance that non-sister chromatids would cross over in the region between the genes. By working out the number of recombinants it is possible to obtain a measure for the distance between the genes. This distance is called a genetic map unit (m.u.), or a centimorgan and is defined as the distance between genes for which one product of meiosis in 100 is recombinant. A recombinant frequency (RF) of 1 % is equivalent to 1 m.u. A linkage map is created by finding the map distances between a number of traits that are present on the same chromosome, ideally avoiding having significant gaps between traits to avoid the inaccuracies that will occur due to the possibility of multiple recombination events.

Linkage mapping is critical for identifying the location of genes that cause genetic diseases. In an ideal population, genetic traits and markers will occur in all possible combinations with the frequencies of combinations determined by the frequencies of the individual genes. For example, if alleles A and a occur with frequency 90% and 10%, and alleles B and b at a different genetic locus occur with frequencies 70% and 30%, the frequency of individuals having the combination AB would be 63%, the product of the frequencies of A and B, regardless of how close together the genes are. However, if a mutation in gene B that causes some disease happened recently in a particular subpopulation, it almost always occurs with a particular allele of gene A if the individual in which the mutation occurred had that variant of gene A and there have not been sufficient generations for recombination to happen between them (presumably due to tight linkage on the genetic map). In this case, called linkage disequilibrium, it is possible to search potential markers in the subpopulation and identify which marker the mutation is close to, thus determining the mutation's location on the map and identifying the gene at which the mutation occurred. Once the gene has been identified, it can be targeted to identify ways to mitigate the disease.

http://en.wikipedia.org/wiki/Genetic_mapping