title: Haplotypic determinants of instability in the FRAX region: Concatenated mutation or founder effect?
abstract: The fragile X triplet repeat expansion at Xq27.3 has been shown to be associated with mutation or instability 600 kb distal at the FMR2 repeat locus. Concatenated mutation, whereby a mutation at one locus somehow interacts with 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 of cladistic groups to more thoroughly define the properties of these haplotypes, and in doing so isolate one group of haplotypes which may be predisposed 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 process describe a previously undefined mutation at FRAXE.
authors: Genetic Epidemiology, Human Genetics, Southampton General Hospital, Southampton, Hampshire, UK. se@soton.ac.uk
authors: S
authors: S
authors: Ennis
authors: A
authors: A
authors: Murray
authors: N E
authors: NE
authors: Morton
mesh_terms: D000483:Alleles; D018703:Founder Effect; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D016015:Logistic Models; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016601:RNA-Binding Proteins; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human