Friday, April 22, 2011

Mapping and Identifying Genes

There are two main mapping approaches to identifying genes on chromosomes: genetic mapping and physical mapping. Genetic mapping relies on observing the recombination frequencies between pairs of polymorphic markers segregating within families. A genetic map is constructed by analysing several pairs of polymorphic genetic markers. The genetic distance between the markers is determined by their recombination frequency and measured in centimorgans (cM), where 1cM equates to 1% recombination, rather than number of nucleotides. For any pair of marker loci, the smaller the recombination frequency, the shorter is the genetic distance between the markers. The process of constructing a genetic map is called linkage analysis; this aims to determine whether or not a pair of gene loci tend to be co-inherited or separated by recombination. At one time, linkage analysis in humans was a slow process because of the dearth of polymorphic markers.However, the discovery of variable numbers of tandem repeat polymorphisms (VNTRs) and the production of genome wide panels of polymorphic microsatellites in the 1990s rendered linkage analysis one of the major tools in the Human Genome Project. Additionally, a number of physical mapping techniques were developed that enabled
genes to be identified and localised purely on the basis of their physical positions along the chromosomes; this became known as ‘reverse genetics’ and later ‘positional cloning’.

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