Mutation and selection in the marker (X) syndrome. A hypothesis

Abstract

Sherman et al. (1984) concluded from a cytogenetic and genetic analysis of families with the marker (X) syndrome that the rate of the mutation leading to this syndrome is extraordinarily high (7.2 X 10(-4) in male germ cells), and that these mutations occur exclusively in male germ cells. It is shown by some model calculations that the empirical evidence can be reconciled with more conventional assumptions on the mutation rate if a moderately increased fertility of clinically unaffected female and possibly male carriers in the past is assumed. Indirect evidence for such an increased fertility can be derived from old reports on higher reproduction of slightly subnormal individuals. On the other hand, complete compensation of gene loss in affected individuals by higher fertility of unaffected carriers appears to be rather unlikely. At present, a moderately high mutation rate--as found, for example, in Duchenne muscular dystrophy or haemophilia A--in combination with a moderately increased fertility of clinically unaffected carriers is the most likely alternative.