Microsatellite Analysis in Human Disease

Microsatellites (or simple sequence length polymorphisms [SSLPs]; and short tandem repeat polymorphisms [STRs]) are tandemly repeated arrays of short stretches of nucleotide sequences, typically (dA-dC/dT-dG), where n is between 15 and 30 (1 ,2 ) The human genome is estimated to contain approximately 12,000 (dA-dC)n microsatellites with a polymorphic information content (PIC) > 0.5 (3 ) Further information on microsatellite orgamzation, distribution, and origin can be obtained from a recent review (4 ). For the purposes of this chapter, it suffices to state that owing to their high heterozygosity, Mendelian codominant inheritance, ubiquity through the genome, and ease of polymerase chain reaction (PCR) typability, microsatellites are the markers of choice in the construction of human (and other model organisms) linkage maps. For instance, a recent human microsatellite linkage map consists of over 5264 (dA-dC)n loci with a heterozygosity >70% distributed along the genome at an average interval of 1.6 centiMorgans (CM) (5 ) This forms an invaluable resource for the genetic dissection of complex traits (e.g., type I diabetes).