Insert size and flanking haplotype in fragile X and normal populations: possible multiple origins for the fragile X mutation.
A number of recent studies have found non-random association between the fragile X mutation and genotypes for the closest-linked flanking markers, suggesting either a limited number of 'founder' mutations or, alternatively, a predisposing haplotype for the fragile X expansions. Using three microsatellite markers within 150 kb of FRAXA, we have compared haplotypes in a series of fragile X males and in a control population and find a markedly different distribution in the two samples, with apparently greater haplotype diversity in the fragile X sample. In the control sample, various non-random associations of CGG repeat numbers with flanking haplotypes were recorded which provide a clue to the likely origins of the fragile X mutation, suggesting more than one mechanism for the initial expansion event.
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Wiltshire, UK.
J N
JN
Macpherson
H
H
Bullman
S A
SA
Youings
P A
PA
Jacobs
D004276:DNA, Satellite; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid
D004276:DNA, Satellite; D005819:Genetic Markers