Dominance (genetics) - Dominant and Recessive Genetic Diseases in Humans

Dominant and Recessive Genetic Diseases in Humans

In humans, many genetic traits or diseases are classified simply as "dominant" or "recessive." Especially with respect to so-called recessive diseases, this can oversimplify the underlying molecular basis and lead to misunderstanding of the nature of dominance. For example, the genetic disease phenylketonuria (PKU) results from any of a large number (>60) of alleles at the gene locus for the enzyme phenylalanine hydroxylase (PAH). Many of these alleles produce little or no PAH, as a result of which the substrate phenylalanine and its metabolic byproducts accumulate in the central nervous system and can cause severe mental retardation if untreated.

The genotypes and phenotypic consequences of interactions among three alleles are shown in the following table:

Genotype PAH activity conc PKU ?
AA 100% 60 uM No
AB 30% 120 uM No
CC 5% 200 ~ 300 uM Hyperphenylalaninemia
BB 0.3% 600 ~ 2400 uM Yes

In unaffected persons homozygous for a standard functional allele (AA), PAH activity is standard (100%), and the concentration of phenylalanine in the blood is about 60 uM. In untreated persons homozygous for one of the PKU alleles (BB), PAH activity is close to zero, ten to forty times standard, and the individual manifests PKU.

In the AB heterozygote, PAH activity is only 30% (not 50%) of standard, blood is elevated two-fold, and the person does not manifest PKU. Thus, the A allele is dominant to the B allele with respect to PKU, but the B allele is incompletely dominant to the A allele with respect to its molecular effect, determination of PAH activity level (0.3% < 30% << 100%). Finally, the A allele is an incomplete dominant to B with respect to, as 60 uM < 120 uM << 600 uM. Note once more that it is irrelevant to the question of dominance that the recessive allele produces a more extreme phenotype.

For a third allele C, a CC homozygote produces a very small amount of PAH enzyme, which results in a somewhat elevated level of in the blood, a condition called hyperphenylalaninemia, which does not result in mental retardation.

That is, the dominance relationships of any two alleles may vary according to which aspect of the phenotype is under consideration. It is typically more useful to talk about the phenotypic consequences of the allelic interactions involved in any genotype, rather than to try to force them into dominant and recessive categories.

Read more about this topic:  Dominance (genetics)

Famous quotes containing the words dominant and, dominant, genetic, diseases and/or humans:

    The dominant and most deep-dyed trait of the journalist is his timorousness. Where the novelist fearlessly plunges into the water of self-exposure, the journalist stands trembling on the shore in his beach robe.... The journalist confines himself to the clean, gentlemanly work of exposing the griefs and shames of others.
    Janet Malcolm (b. 1934)

    The dominant metaphor of conceptual relativism, that of differing points of view, seems to betray an underlying paradox. Different points of view make sense, but only if there is a common co-ordinate system on which to plot them; yet the existence of a common system belies the claim of dramatic incomparability.
    Donald Davidson (b. 1917)

    We cannot think of a legitimate argument why ... whites and blacks need be affected by the knowledge that an aggregate difference in measured intelligence is genetic instead of environmental.... Given a chance, each clan ... will encounter the world with confidence in its own worth and, most importantly, will be unconcerned about comparing its accomplishments line-by-line with those of any other clan. This is wise ethnocentricism.
    Richard Herrnstein (1930–1994)

    Arrogance, pedantry, and dogmatism ... the occupational diseases of those who spend their lives directing the intellects of the young.
    Henry S. Canby (1878–1961)

    It is quite a common and vulgar thing among humans to understand, foresee, know and predict the troubles of others. But oh what a rare thing it is to predict, know, foresee and understand one’s own troubles.
    François Rabelais (1494–1553)