If a marker allele and disease mutation lie close together on the same chromosome they are unlikely to be separated by crossovers during meiosis.
Genetic linkage is the phenomenon whereby alleles at loci close together on the same chromosome will tend to be inherited together, because it will be rare for a crossover to occur between the loci at meiosis.
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If a marker allele and disease mutation lie close together on the same chromosome they are unlikely to be separated by crossovers during meiosis. |
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In the first pedigree, the disease cosegregates with an A allele of the marker. In the second pedigree, the disease initially cosegregates with a B allele until there is a recombination, after which it cosegregates with a C allele. |
Linkage can be used to map disease genes by typing polymorphic DNA markers to see if their alleles cosegregate with disease among related subjects. The strength of evidence in favour of linkage can be measured as the lod score which is the logarithm (base 10) of the likelihood ratio in favour of linkage. Traditionally a lod of 3 is taken as good evidence for linkage.
There are problems applying the lod score method to complex traits, and a common alternative is to examine marker allele-sharing between pairs of affected relatives, for example using the sib-pair method.
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The second sib pair shares one allele IBD, while all the others share both alleles, suggesting a recessive gene may be quite closely linked to the marker. |
If relative pairs share marker alleles more often than would be expected by chance, this suggests that a susceptibility locus may be linked to the marker.
Linkage is a very long range phenomenon, so that only 2-300 anonymous markers may be sufficient to screen the whole genome.
