25.6: Genetic Mapping
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Because the frequency of recombination between two loci (up to 50%) is roughly proportional to the chromosomal distance between them, we can use recombination frequencies to produce genetic maps of all the loci along a chromosome and ultimately in the whole genome. The units of genetic distance are called map units (mu) or centiMorgans (cM), in honor of Thomas Hunt Morgan by his student, Alfred Sturtevant , who developed the concept. Geneticists routinely convert recombination frequencies into cM: the recombination frequency in percent is approximately the same as the map distance in cM. For example, if two loci have a recombination frequency of 25% they are said to be ~25cM apart on a chromosome (Figure \(\PageIndex{9}\)). Note: this approximation works well for small distances (RF<30%) but progressively fails at longer distances because the RF reaches a maximum at 50%. Some chromosomes are >100 cM long but loci at the tips only have an RF of 50%. The method for mapping of these long chromosomes is shown below.
Note that the map distance of two loci alone does not tell us anything about the orientation of these loci relative to other features, such as centromeres or telomeres, on the chromosome.
Map distances are always calculated for one pair of loci at a time. However, by combining the results of multiple pairwise calculations, a genetic map of many loci on a chromosome can be produced (Figure \(\PageIndex{10}\)). A genetic map shows the map distance, in cM, that separates any two loci, and the position of these loci relative to all other mapped loci. The genetic map distance is roughly proportional to the physical distance, i.e. the amount of DNA between two loci. For example, in Arabidopsis , 1.0 cM corresponds to approximately 150,000bp and contains approximately 50 genes. The exact number of DNA bases in a cM depends on the organism, and on the particular position in the chromosome; some parts of chromosomes (“crossover hot spots”) have higher rates of recombination than others, while other regions have reduced crossing over and often correspond to large regions of heterochromatin.
When a novel gene or locus is identified by mutation or polymorphism, its approximate position on a chromosome can be determined by crossing it with previously mapped genes, and then calculating the recombination frequency. If the novel gene and the previously mapped genes show complete or partial linkage, the recombination frequency will indicate the approximate position of the novel gene within the genetic map. This information is useful in isolating (i.e. cloning) the specific fragment of DNA that encodes the novel gene, through a process called map-based cloning .
Genetic maps are also useful to track genes/alleles in breeding crops and animals, in studying evolutionary relationships between species, and in determining the causes and individual susceptibility of some human diseases.
Genetic maps are useful for showing the order of loci along a chromosome, but the distances are only an approximation. The correlation between recombination frequency and actual chromosomal distance is more accurate for short distances (low RF values) than long distances. Observed recombination frequencies between two relatively distant markers tend to underestimate the actual number of crossovers that occurred. This is because as the distance between loci increases, so does the possibility of having a second (or more) crossovers occur between the loci. This is a problem for geneticists, because with respect to the loci being studied, these double-crossovers produce gametes with the same genotypes as if no recombination events had occurred (Figure \(\PageIndex{11}\)) – they have parental genotypes. Thus a double crossover will appear to be a parental type and not be counted as a recombinant, despite having two (or more) crossovers. Geneticists will sometimes use specific mathematical formulae to adjust large recombination frequencies to account for the possibility of multiple crossovers and thus get a better estimate of the actual distance between two loci.