Mapping

There are four major kinds of genetic markers that have been used for genetic mapping. The oldest of these is the restriction fragment length polymorphism (RFLP) that was first proposed for genetic mapping in 1980. RFLPs arise from changes in a single base pair that can be detected by restriction endonuclease enzymes. These enzymes can cut the DNA at that locus if the right base pair is present. Many maps were made with these markers, but they are expensive and time-consuming to genotype, and they generally have only two alleles. Having only two alleles means that in many cases it is impossible to tell the two chromosomes in any person apart for that marker and makes that marker useless for genetic mapping in that family. In the figure, the mother of the eight children has the same alleles at locus 1, the same alleles at locus 2, and the same alleles at locus 3. Thus we cannot tell if there have been any recombination events coming from the mother. RFLPs were the first type of marker known to occur almost everywhere, across all the chromosomes.

Variable number of tandem repeat (VNTR) markers were the next markers to be described. These result from the duplication of DNA sequences consisting of 50 to 5,000 base pairs each. The differences between the two homologous chromosomes are in the number of repeats present (and thus the length of the locus). These markers are expensive and time consuming to genotype but have the advantage of having many alleles (often more than twenty). Thus almost everyone in the world has a different allele on each paired chromosome at a VNTR locus. This allows more families to give recombination information. Having so many alleles, however, can cause problems, because it can be hard to tell many of the alleles apart during genotyping. VNTRs also tend to occur most often at the ends of chromosomes, not in the middle. This is unlike RFLPs, which occur at all locations on a chromosome.

Microsatellite markers—also known as simple tandem repeat polymorphisms (STRPs), simple sequence repeats (SSRs), or simple sequence length polymorphisms (SSLPs)—have become the most common type of marker for genetic maps. These markers are made of repeats of two, three, or four base pairs, with the variation being the number of repeats. For example, the most commonly used two-base-pair repeat is CA, and the most commonly used four-base-pair repeat is GATA. Thus a microsatellite marker actually varies in length between the paired chromosomes. On one chromosome, there might be eight repeats (CACACACACACACACA), while on the other chromosome there might be ten (CACACACACACACACACACA). Microsatellite markers are easy to genotype and have multiple (three to ten) but usually not large numbers (more than ten) of alleles. They also occur almost everywhere across the chromosome. Most of the genetic maps in use today are made with microsatellite markers.

The most recently described type of marker is the single nucleotide polymorphism (SNP, pronounced "snip"). As the name implies, these are variations at a single base on the chromosome. For example, on some chromosomes a locus might have a C, while on other chromosomes the same locus might have a T. These are the most common markers, with at least three million already described, and seem to occur across the entire genome. As with RFLPs, there are almost always only two alleles at a SNP locus. Individually they suffer the same problem as RFLPS of not being useful in many of the families. They are being used widely now because they are very easy to genotype, are very common (occurring at least ten times more frequently than the other types of markers) and thus can be used in combination with each other.