title: An n-allele model for progressive amplification in the FMR1 locus.
abstract: An n-allele model is developed for the FMR1 locus, which causes the fragile X syndrome, where n is the number of triplet repeats in the first exon. Frequencies in the general population and in index families are used to generate an n to n + delta transition matrix that predicts specific risks in satisfactory agreement with observation. However, until sequencing distinguishes between stable and unstable alleles with the same value of n, it is premature to infer whether allelic frequencies at the FMR1 locus are at equilibrium or, as some have suggested, are evolving toward higher frequencies of the pathogenic allele.
authors.affiliation: Human Genetics Group, University of Southampton, Level G, Princess Anne Hospital, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Morris
authors.forename: N E
authors.initials: NE
authors.lastname: Morton
authors.forename: A
authors.initials: A
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Macpherson
authors.forename: D
authors.initials: D
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Sherman
mesh_terms: D000483:Alleles; D005091:Exons; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D008957:Models, Genetic; D008962:Models, Theoretical; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011336:Probability; D016601:RNA-Binding Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human