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

Area of Science:

• Human Genetics
• Medical Genetics
• Population Genetics

Background:

• Previous studies suggested an extraordinarily high mutation rate for marker (X) syndrome, exclusively in male germ cells.
• This high rate presented challenges in reconciling with existing genetic models and empirical data.
• Alternative explanations involving carrier fertility were proposed but lacked direct evidence.

Purpose of the Study:

• To re-evaluate the mutation rate of marker (X) syndrome.
• To explore alternative hypotheses, including increased carrier fertility, to explain observed family data.
• To reconcile empirical evidence with more conventional mutation rate assumptions.

Main Methods:

• Cytogenetic and genetic analysis of families with marker (X) syndrome.
• Model calculations to assess the impact of varying mutation rates and fertility assumptions.
• Review of historical reproductive data for individuals with subnormal traits.

Main Results:

• The original conclusion of an exceptionally high mutation rate (7.2 X 10(-4)) in male germ cells was questioned.
• Model calculations indicated that a moderately high mutation rate, similar to Duchenne muscular dystrophy or hemophilia A, could explain the data.
• This was achievable if a moderately increased fertility of clinically unaffected female and possibly male carriers was assumed historically.
• Indirect evidence from older reports suggested higher reproduction rates in slightly subnormal individuals.

Conclusions:

• Complete compensation of gene loss by carrier fertility is unlikely.
• A combination of a moderately high mutation rate and moderately increased carrier fertility is the most probable explanation for marker (X) syndrome inheritance patterns.
• This revised model offers a more parsimonious explanation compared to an extraordinarily high mutation rate.