Genetics

Biochemistry/MCB 568 -- Fall 2007
John W. Little--University of Arizona

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Some terminology:

Dominance test

The concept of dominance was discussed in class. This is a genetic test that can give considerable insight into the mechanisms by which mutations change the function of a protein.

To do a dominance test, one uses genetic methods to make a cell containing one copy of the wild-type allele of a gene, and one copy of a mutant allele, symbolized  +/m. One then examines the behavior or phenotype of this cell and compares it with the phenotype of the wild-type and mutant cells.

If the +/m cell has the same phenotype as the wild-type, the mutation is said to be recessive to wild-type. Note that almost all mutations that abolish function ("knockout mutations") are recessive to wild-type. Hence, a dominance test can help you identify whether a mutation is a knockout mutation.

If the +/m cell has the same phenotype as the mutant, the mutation is said to be dominant to wild-type. This behavior often means that the mutant protein can continue to function under a condition in which the wild-type protein cannot.  

Epistasis test 

Epistasis tests are used to order events in a regulatory pathway.

To do an epistasis test, one constructs a strain containing mutations in two different genes. Individually, these mutations must confer different phenotypes on the cell for the test to be interpretable. One then determines the phenotype of the double mutant and compares it to that of the single mutant. If the phenotype of the double mutant is like that of one of the single mutants, we say that the latter mutation is epistatic to the other one.

Example: Suppose mutation A makes a gene regulatory circuit non-inducible, while mutation B makes it constitutive. If the A - B double mutant is constitutive, B is epistatic to A. In this case, we can infer that B lies downstream in the regulatory pathway from A.

Note that the interpretation of an epistasis test is different from this in a metabolic pathway. In this case, the epistatic gene lies upstream of the other one.

Note also that, if B is epistatic to A, then one can't tell from the phenotype whether A is mutant or wild-type.