The Praxitype: An Improved Interpretation of Genotype-Phenotype Variation

Vincent M. Riccardi*

The Praxitype: An Improved Interpretation of Genotype-Phenotype Variation

It is hard to imagine anything more complicated than the organization
and function of the mammalian-especially human nervous system.

For a while it seemed simplified by single gene mutations being the basis for
complex neurological disorders: specify the mutated gene and “everything was accounted for.”

A bit more thought and experience made it clear that this was an
over-simplification: HOW the mutant gene was expressed was at
least as much of a factor as WHICH gene was mutated.

Obviously, there were myriad superimposed factors, especially genetic ones.
In short, the HOW of gene expression is largely explained by epigenetic factors,
such as microRNA, the “availability” of the gene (mutant or otherwise),
regulatory biochemical networks (e.g., Ras), etc.

That is, we no longer can rely on the genotype, the
“what” of pathogenesis: we also need insight into the “How.”

I have specified the latter as the Praxitype! Thus, when we look to
assess, to evaluate neurological disorders from a genetic vantage
point-that is, in terms of “genome variation”- there is more to
it than the Genotype, the allele at a specific genetic locus.

What follows is an introduction to what is beyond the genotype that
addresses genome variation and how genes are fully manifest,
critical for understanding genetic neurological disorders!

The phrase, “Genome Variation,” implies, if not declares, that the relationship
of the details regarding an individual’s genome (i.e., genotype) to the details
of that individual’s combination of traits (i.e., phenotype) is variable,
sometimes to the point of being confusing or even incomprehensible.

Neuro Open J. 2019; 6(1): 10-12. doi: 10.17140/NOJ-6-131