title: Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes.
abstract: In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragile X chromosomes. Contrary to observations made in myotonic dystrophy, fragile X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. We propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen.
authors.affiliation: Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Oudet
authors.forename: E
authors.initials: E
authors.lastname: Mornet
authors.forename: J L
authors.initials: JL
authors.lastname: Serre
authors.forename: F
authors.initials: F
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Lentes-Zengerling
authors.forename: C
authors.initials: C
authors.lastname: Kretz
authors.forename: C
authors.initials: C
authors.lastname: Deluchat
authors.forename: I
authors.initials: I
authors.lastname: Tejada
authors.forename: J
authors.initials: J
authors.lastname: Boué
authors.forename: A
authors.initials: A
authors.lastname: Boué
mesh_terms: D000483:Alleles; D004276:DNA, Satellite / Q000032:analysis; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016296:Mutagenesis; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers