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Family linkage studies

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Family linkage studies rely on the principle of genetic linkage: that two fragments of the genome which are found close to each other on a parental chromosome will be found together in the offspring more often that predicted by chance.

Hence, in linkage studies, two genes are considered. One is the gene for the disease trait, the locus of which is not known. The other is a marker trait, the locus of which is known. Examples of marker traits are blood groups and serum enzyme polymorphisms.

The more often the disease trait and marker appear together in pedigrees, the more likely that they are in close proximity upon one chromosome. If the disease and marker loci are on different chromosomes, then they are just as likely to occur apart as together in the offspring according to the rules of independent assortment.

Logically, a large number of individuals have to be analysed before linkage attains statistical significance. This is expressed as the logarithm of odds, or Lod, score.

If the position of a gene is ascertained relative to two markers, its relative locus along a chromosome can be deduced. A confounding variable that must be considered in such calculations is the crossover of genes in meiosis between pairs of chromosomes.

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