Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Genetic Dominance: Genotype-Phenotype Relationships

In some instances, offspring can demonstrate a phenotype that is outside the range defined by both parents. In particular, the phenomenon known as overdominance occurs when a heterozygote has a more extreme phenotype than that of either of its parents. Indeed, in a few examples, a trait that shows overdominance sometimes confers a survival advantage in the heterozygote (Parsons & Bodmer, 1961).

A well-known example of overdominance occurs in the alleles that code for sickle-cell anemia. Sickle-cell anemia is a debilitating disease of the red blood cells, wherein a single amino acid deletion causes a change in the conformation of a person's hemoglobin such that the person's red blood cells are elongated and somewhat curved, taking on a sickle shape. This change in shape makes the sickle red blood cells less efficient at transporting oxygen through the bloodstream.

The altered form of hemoglobin that causes sickle-cell anemia is inherited as a codominant trait. Specifically, heterozygous (Ss) individuals express both normal and sickle hemoglobin, so they have a mixture of normal and sickle red blood cells. In most situations, individuals who are heterozygous for sickle-cell anemia are phenotypically normal. Under these circumstances, sickle-cell disease is a recessive trait. Individuals who are homozygous for the sickle-cell allele (ss), however, may have sickling crises that require hospitalization. In severe cases, this condition can be lethal.

Producing altered hemoglobin can be beneficial for inhabitants of countries afflicted with falciparum malaria, an extremely deadly parasitic disease. Sickle blood cells "collapse" around the parasites and filter them out of the blood. Thus, people who carry the sickle-cell allele are more likely to recover from malarial infection. In terms of combating malaria, the Ss genotype has an advantage over both the SS genotype, because it results in malarial resistance, and the ss genotype, because it does not cause sickling crises. This complex example of overdominance may be the sole reason that the allele persists in the human population today (Keeton & Gould, 1986).

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Hereditary Spherocytosis And Hemolytic Anemia

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