Mutation harmful dominant

If a mutation is lethal, a homozygote will not survive and will be lost in an early (and usually undetected) spontaneous abortion. Healthy individuals carry as many as ten lethal recessive mutations as well as at least 3-5 autosomal recessive mutations of a seriously harmful type. Harmful dominant mutations are also frequent in the population. These include an elevated lipoprotein content of the blood and an elevated cholesterol level which are linked to early heart disease. 

The spectrum of mutational effects runs the gamut of bodily processes. Genes affect all structures and functions, and so do mutations. The impact ranges from trivial to tragic. Depending on the dominance and severity of a mutation, its effect may be immediate or spread over an enormous period. It is therefore impossible to describe in detail or to quantify all the consequences of an increase in the mutation rate. One generalization is apt, however the net effect of an increase in mutation rate is harmful, because almost all mutants with any detectable effect cure deleterious. 

In the early generations after a pulse of new mutation, the impact is large, but very rapidly diminishes as the most harmful mutants are eliminated. Then there is a very long period when mutants with mild effects or recessive inheritance continue to exert their influence after the severe dominant mutants have been eliminated. If the environment improves, the average impact of the mutant genes diminishes. There will be an imperfect but positive correlation between the diminution in social impact of a mutant gene and its effect on fitness. The total hatched area of the lower graph is somewhat less if the curves were extended indefinitely, the areas would be approximately equal. However, in the future the environment may not continue to improve, but may fluctuate between improvement and decay. 

All these considerations suggest that the policy of concentrating on dominantly inherited diseases, as in the BEIR and UNSCEAR reports, takes into account the major effects of mutation in immediate generations. The harm to one generation from neglecting other factors is very small. We can hope that better understanding of the more subtle effects will occur before any substantial harm has been done by neglecting them. 

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