Tuesday, March 01, 2011

Why call "dominant" traits that are not?

(Readers without interest and background in biology or medicine are advised to skip this post.)
I am now preparing a lecture about Mendelian genetics and I included there the hereditary disorder achondroplasia as an example. All textbooks known to me describe it as a "dominant" condition, so I automatically put it under the headline "complete dominance". Then I started thinking on the subject and finally moved the slide below, to "incomplete dominance".
Why did I change my mind? Because, by definition, an allele is dominant when homozygous and heterozygous individuals having it are indistinguishable. However, in the case of achondroplasia, they are very much distinguishable: homozygous achondroplasia brings early death caused by "breathing failure due to constriction by a tiny chest cage and neurologic problems from hydrocephalus". So the surviving heterozygotes have a phenotype intermediate between that of the two homozygotes - the classical situation of incomplete dominance.
It is clear that, to determine whether we are dealing with complete or incomplete dominance, we must know the phenotype of both heterozygotes. However, in medical genetics, "dominant" is often used to designate any condition caused by a single allele, even if nobody has an idea what the mutant homozygotes would look like. In fact, medical geneticists have a working definition of "dominant" as "a pattern of inheritance in which an affected individual has one copy of a mutant allele and one normal allele". This is understandable in the context of past decades, when there was little chance to study the mutant homozygotes. However, with today's vast database of cases from all over the globe and the opportunity to create transgenic animal models, studying them has become quite realistic. So I think it is high time to sort out this matter.

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