FRAXA AND FRAXE - EVIDENCE AGAINST SEGREGATION DISTORTION AND FOR AN EFFECT OF INTERMEDIATE ALLELES ON LEARNING-DISABILITY

There have been several claims of segregation distortion (meiotic driv e) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linke d loci FRAXA and FRAXE, We found no evidence of meiotic drive in femal es and no convincing evidence in males, where the limitation of risk t o daughters creates a testing bias for alleles of interest. Alleles fo r pre-and full mutation, intermediate alleles, and common alleles were analyzed separately, with the same negative results that are extended in the discussion to claims of meiotic drive for other diseases, On t he other hand, an excess risk of learning difficulties was confirmed f or intermediate FRAXA alleles (relative risk, 2.58 +/- .74) and sugges ted for intermediate FRAXE alleles. The penetrance of learning difficu lty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles, Because of their lower gene frequen cy, full mutations are a less frequent cause of learning difficulty th an intermediate alleles, which contribute .0020 to total prevalence an d .0012 to attributable prevalence of learning difficulty.