THE MUTATION RATE INCREASES WITH AGE AND AT A RATE MUCH FASTER THAN LINEAR : THE GREATEST MUTATIONAL HAZARD IS FERTILE OLD MALES.

James F. Crow studied the dominant large gene mutations and the X-linked mutations. Not the tiny Copy number variations in multigenetic disorders such as schizophrenia, autism and autoimmune disorders.

Paternal Age Effect

How can we account for a higher mutation rate in males than in females? The most obvious explanation lies in the much greater number of cell divisions in the male germ line than in the female germ line. In the female the germ cell divisions stop by the time of birth and meiosis is completed only when an egg matures. In the male, cell divisions are continuous and many divisions have occurred before a sperm is produced. If mutation is associated with cell division, as if mutations were replication errors, we should expect a much higher mutation rate in males than in females.

This makes the strong prediction that the mutation rate should increase with the age of the father, since the older the man, the more cell divisions have occurred. On the other hand, there should be no age effect in females.



I conclude that for a number of diseases the mutation rate increases with age and at a rate much faster than linear. This suggests that the greatest mutational health hazard in the human population at present is fertile old males.