FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability

Proceedings of the National Academy of Sciences of the United States of America
J W TeagueP A Jacobs

Abstract

There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linked loci FRAXA and FRAXE. We found no evidence of meiotic drive in females and no convincing evidence in males, where the limitation of risk to daughters creates a testing bias for alleles of interest. Alleles for 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 the other hand, an excess risk of learning difficulties was confirmed for intermediate FRAXA alleles (relative risk, 2.58 +/- .74) and suggested for intermediate FRAXE alleles. The penetrance of learning difficulty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles. Because of their lower gene frequency, full mutations are a less frequent cause of learning difficulty than intermediate alleles, which contribute .0020 to total prevalence and .0012 to attributable prevalence of learning difficulty.

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Citations

Dec 29, 1998·Trends in Genetics : TIG·G R SutherlandR I Richards
Apr 12, 2012·European Journal of Human Genetics : EJHG·Cheryl ShoubridgeJozef Gecz
Jun 14, 2000·Journal of Medical Genetics·S A YouingsP Jacobs
Jan 22, 2015·Intractable & Rare Diseases Research·Reymundo LozanoRandi J Hagerman
Apr 22, 2006·Annals of Human Genetics·S EnnisP A Jacobs
Sep 24, 2004·Neuropsychologia·Caroline J MooreDeclan G M Murphy
Apr 23, 2004·American Journal of Medical Genetics. Part a·Eran ZunzMordechai Shohat
Dec 31, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Sarah SnanoudjNicolas Richard
Dec 3, 1999·American Journal of Medical Genetics·A D Paterson, A Petronis

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