theories of dominance

Dr. James R. Garey garey at CCIT01.DUQ.EDU
Fri Mar 26 14:51:24 EST 1993


I teach a genetics class and spend a lot of time explaining dominance  
at the mendelian level compared to the molecular level.  Two things  
come to mind that might be relevant to the discussion.  


What I try to get across to my students is that there are no simple  
rules for predicting the molecular mechanism behind observed  
inheritance patterns. To me, this is the fun part of genetics.  
Genetics texts have a tendency to (figuratively) wave their arms  
around when explaining mechanisms behind co-dominance, incomplete  
dominance etc in the section on mendalian genetics, and never picking  
up the same thread or examples when in later sections they discuss  
molecular mechanisms of genetic traits.  I try to give lots of  
examples of molecular mechanisms behind various transmittance  
patterns.  


	My favorite one is in the Klug and Cummings genetics text and   
is different than the mechanisms I've seen posted on this subject.

Some genetic defects of collagen appear to be dominant by the  
following mechanism: 3 identical polypeptide chains assemble into the  
tropocollagen subunit.  If one allele makes normal polypeptide chains  
and the other makes defective chains, the dominance appears after  
assembly of the tropocollagen.  1/2 of the chains are normal, 1/2 of  
the chains defective.  it only takes one defective chain of the three  
in the tropomyosin subunit to result in abnormal collagen.   
Therefore:

1/2 x 1/2 x 1/2  = 1/8 normal tropomyosin
which leaves 7/8 abnormal tropomyosin

So one/half mutant allele products leads to 7/8 defective collagen  
which we would observe as dominant.    


	Another disease (one I used to work with) is an enzymatic  
defect of heme biosynthesis called porphyria cutanea tarda.  It is  
caused by a variety of mutations which resulted in either no gene  
product from the defective allele, or inactive gene product from the  
defective allele.  The disease was usually described in the  
literature as autosomal dominant, but in reality it was much more  
complicated.  For one thing it was usually (prenatally) lethal when  
homozygous but very occasionally people would live into adulthood,  
but with more severe symptoms than the heterozygotes.  Thus, the  
disease was recessive for the severe phenotype but dominant for the  
less severe phenotype (as in sickle cell disease vs trait).  The  
medical community got around this by giving the heterozygote form of  
the disease a different name than the homozyous form of the disease.   
Other complications were whether the heterozygous form of the disease  
was incomplete dominance (true if the particular mutation resulted in  
no gene product) or codominance (true if the particular mutation  
resulted in inactive gene product).  Also, most heterozygotes never  
showed clinical symptoms, and could only be identified by molecular  
or biochemical tests. The medical community just ignored all of this  
complicated stuff and continues to call the disease an autosomal  
dominant trait.  I personally am not sure what you should call it,  
but it certainly illustrates how mendelian and "neo" mendelian   
concepts are usually simplifications of very complex processes, and  
that even within one trait, there are often sub-traits caused by  
different mutations.  I think some new terminology will have to be  
invented as we learn more about these kinds of things.
  Jim Garey   Duquesne University



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