Sometimes, alleles occur that, when present in two copies, are lethal to the individual; the affected individual usually dies in embryonic development. This lethality affects the phenotypic ratio, such that it appears not to conform to a standard 3 : 1 Mendelain ratio for a single gene.

An example of this is a gene for coat color in mice. Two alleles of this gene are agouti, which confers a gray-brown coat color, and yellow, which confers (as you might guess) a yellow coat color. If an agouti mouse is crossed witha yellow mouse, half of the offspring are yellow, and half are agouti:

Where have you seen a 1 : 1 ratio like this before? If you can't recall, I'll give you a hint. That suggests that one of the P1 mice is a heterozygote, and one of the mice is homozygous recessive. Let's see what happens when we mate two of the F1 yellow mice with each other:

This cross yields a 2 : 1 ratio in the F2. (???) How does this ratio arise? This result can be explained the following way: yellow is dominant to agouti, but yellow in the homozygous condition is embryonic lethal. Therefore, any yellow mice observed must be heterozygotes. The first cross shown above would therefore be:

When F1 yellow mice are mated, it becomes like a monohybrid cross: Yy X Yy. This should yield a standard Mendelian ratio of 3/4 yellow : 1/4 agouti. However, 1/3 of the yellow mice will never be born, because they are homozygous for the Y allele. So the result of this cross is the following:

Since the last group is never born, they are not counted in actually determining the phenotypic ratio. Of the surviving mice, 1/3 are agouti, and 2/3 are yellow, just as observed.

To get more experience dealing with lethal alleles, go to Virtual Flylab, and cross a wild-type fly with a fly that has stubble bristles, star-shaped eyes, or diachete wings. From the offspring, mate two flies that show the mutant phenotype.

A slightly different type of lethal allele found in humans is that for Huntington's disease. The allele for Huntington's is dominant, so only one copy is needed for the disease to occur. In contrast to the above example of a lethal allele, Huntington's is not lethal in the embryo. Instead, the disease usually occurs when the person is in their thirties or forties. Unfortunately, Huntington's is invariably lethal, and the victim experiences gradual neural degeneration and mental deterioration for 10 to 15 years after onset, before death finally occurs.