Genetics of mitral valve prolapse and its clinical impact

Mendelian Ratios And Lethal Genes

Figure 1: Castle's experimental results.

These results suggest that some alleles are lethal.

In 1905, Lucien Cuénot observed unusual patterns when studying inheritance of a coat color gene in mice. After mating two yellow mice, he observed that the offspring never showed a normal 3:1 phenotypic ratio. Instead, Cuénot always observed a 2:1 ratio, with two yellow mice for every one non-yellow mouse (Cuénot, 1905; Paigen, 2003). Cuénot thus determined that yellow coat color was the dominant phenotypic trait, and by using test crosses, he showed that all his yellow mice were heterozygotes. However, from his many crosses, Cuénot never produced a single homozygous yellow mouse. How could this be?

Shortly thereafter, in 1910, W. E. Castle and C. C. Little confirmed Cuénot's unusual segregation ratios (Figure 1). Moreover, they demonstrated that Cuénot's crosses resulted in what appeared to be non-Mendelian ratios because he had discovered a lethal gene. Castle and Little did this by showing that one-quarter of the offspring from crosses between heterozygotes died during embryonic development (Castle & Little, 1910; Paigen, 2003). This was why Cuénot never observed homozygous yellow mice! Thus, by considering embryonic lethality, or death, as a new phenotypic class, the classic 1:2:1 Mendelian ratio of genotypes could be reestablished (Figure 2).

As these examples illustrate, lethal genes cause the death of the organisms that carry them. Sometimes, death is not immediate; it may even take years, depending on the gene. In any case, if a mutation results in lethality, then this is indicative that the affected gene has a fundamental function in the growth, development, and survival of an organism.

Lethal genes can be recessive, as in the aforementioned mouse experiments. Lethal genes can also be dominant, conditional, semilethal, or synthetic, depending on the gene or genes involved. The following sections explore these variations in detail.

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