Haplotypic determinants of instability in the FRAX region: Concatenated mutation or founder effect?

The fragile X triplet repeat expansion at Xq27.3 has been shown to be assoc iated with mutation or instability 600 kb distal at the FMR2 repeat locus. Concatenated mutation, whereby a mutation at one locus somehow interacts wi th mutation, recombination, deletion, or transposition at another locus, is a possible explanation. In this study we examine evidence from a sample of over 7,000 independent haplotypes from the FRAX region. We adopt the use o f cladistic groups to more thoroughly define the properties of these haplot ypes, and in doing so isolate one group of haplotypes which may be predispo sed to the phenomenon of concatenated mutation. Distinguishing concatenated mutation from founder effects is difficult within a single population. We present our evidence for and against concatenated mutation, and in the proc ess describe a previously undefined mutation at FRAXE. Hum Mutat 18:61-69, 2001. (C) 2001 Wiley-Liss, Inc.