Is the new mutation allelic to a previously described mutation

Clinical and histological evaluation of a new mutation is sometimes reminiscent of other, previously characterized mouse mutations. In this case, and only if the new mutation is recessive, it is possible to prove or to disregard the hypothesis that this mutation is a new allele (or remutation) at the same locus as one of the known mutations. The principle is that mice heterozygous for both mutations will show an abnormal phenotype if the two mutations affect the same gene, whereas they will appear normal if they affect different genes.

Practically, either known heterozygous or homozygous mice of the new mutation are mated with either known heterozygous or homozygous mice of the known mutation. The observation that a fraction of the progeny show an abnormal phenotype close to that of either parental mutant demonstrates that the two mutations affect the same gene. If the two mutations are allelic, the mating of a mouse homozygous for one mutation with a mouse homozygous for the other should yield only affected progeny. If one of the two parents is homozygous for one mutation and the other is heterozygous for the other, an equal proportion of affected and phenotypically normal progeny should be obtained. Finally, if the parents are heterozygous for different mutations that are allelic, one littermate out of four should be affected.

In the case of semidominant or dominant mutations, proving allelism is much more difficult to achieve and will be based on (1) identical map position and (2) either the occurrence of a new phenotype, or the frequency of the different classes of phenotypes, when crossing heterozygous mice.

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