The Study of Gene Polymorphisms: How Complex Is Complex Genetic Disease

What is a polymorphism? Strictly speaking, a polymorphism is the occurrence in a population of two or more genetically determined forms in such frequencies that the rarest of them could not be maintained by mutation alone. For our purposes, we are examining polymorphic DNA, so that the polymorphic information content is the amount of variation at a particular site in the DNA. When dealing with complex genetic diseases, particularly for mapping, we often rely on satellite DNA. Satellite DNA is a class of DNA sequences, that separates out on density-gradient centrifugation as a shoulder or “satellite” to the main peak of DNA. Satellite DNA corresponds to 10–15% of the DNA in the human genome consisting of tandemly repeated DNA sequences. Minisatellites (also termed variable numbers of tandem repeats, or VNTR) have repeat units 6–24 basepairs in length, and microsatellites have repeat units of only 1–4 basepairs in length. We rely on microsatellites. Microsatellite DNA consists of polymorphic variation in DNA sequences caused by VNTR of the dinucleotide CA, tri- or tetranucleotides. Microsatellites are generally less than 300 basepairs long. Fortunately for us, there are thousands of microsatellites scattered all along the genome. Every person on earth has microsatellites at precisely the same location as all other persons. However, the microsatellites vary (are polymorph) in terms of their length. A hypothetical example is shown in Fig. 1 .

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