Most Metabolic Diseases Affect Unimportant Genes

 
Okay, so the title is a little bit disingenuous. Obviously metabolic diseases like cystic fibosis, thalasemia, phenylketonuria, and Huntington's Disease are not trivial. They cause devastating problems for patients and family. Many metabolic diseases are lethal. That's not "unimportant."

The point isn't that the genes are "unimportant" in that sense. What I meant is that defects in essential genes—the ones are part of core metabolism—do not usually show up as metabolic defects. The reason is that any defects in, say, RNA polymerase, will usually be embryonic lethals and we will never see them [RNA Polymerase Genes in the Human Genome].

The defects that are most likely to show up as metabolic diseases are those where the defect is not so severe as to prevent embryonic development. Thus, a defect in adult hemoglobin (thalasemia), for example, will only be manifest after birth and even then there are compensating genes that can prevent death. Same with cystic fibrosis. Not to minimize the consequences of the disease, but we only see it as a metabolic defect because it isn't immediately lethal.

The point of this little note is to correct a widespread misconception. Many people think that metabolic diseases identify the most important genes in humans. The ones that are essential for life. In fact that's not usually the case. The really important genes do not have associated metabolic diseases. As a general rule, it's only the second tier of important genes that are associated with metabolic disease. The ones that are not essential for cell survival during fetal development.