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)

    Combativeness was, I suppose, the dominant trait in my grandmother’s nature. An aggressive churchgoer, she was quite without Christian feeling; the mercy of the Lord Jesus had never entered her heart. Her piety was an act of war against Protestant ascendancy. ...The teachings of the Church did not interest her, except as they were a rebuke to others ...
    Mary McCarthy (1912–1989)

    What strikes many twin researchers now is not how much identical twins are alike, but rather how different they are, given the same genetic makeup....Multiples don’t walk around in lockstep, talking in unison, thinking identical thoughts. The bond for normal twins, whether they are identical or fraternal, is based on how they, as individuals who are keenly aware of the differences between them, learn to relate to one another.
    Pamela Patrick Novotny (20th century)

    A fiction about soft or easy deaths ... is part of the mythology of most diseases that are not considered shameful or demeaning.
    Susan Sontag (b. 1933)

    To not be afraid in our world is the message that doesn’t derive from reason, but maybe from this mysterious capacity given to humans which we call—not without a little embarrassment—faith.
    Friedrich Dürrenmatt (1921–1990)