title: Population genetics of the fragile-X syndrome: multiallelic model for the FMR1 locus.
abstract: A model is developed to account for recent molecular observations. It postulates four alleles: normal (N), small rather stable insert (S), larger, unstable insert (Z), and large insert (L). The last-named allele causes the fragile-X phenotype, inactivation of the FMR1 locus by methylation, and mental impairment; the FMR1 locus (for fragile-X mental retardation locus 1) resides in the FRAXA region. When this model is fit to pre-molecular data, the Z allele appears to be no more frequent than L, while the S allele is polymorphic. Predictions of the model are in reasonable agreement with observation and suggest much more powerful tests of molecular data, including the Laird hypothesis that conversion of Z to L does not occur in active X chromosomes.
authors.affiliation: Cancer Research Campaign Research Group in Genetic Epidemiology, University of Southampton, Southampton General Hospital, United Kingdom.
authors.forename: N E
authors.initials: NE
authors.lastname: Morton
authors.forename: J N
authors.initials: JN
authors.lastname: Macpherson
mesh_terms: D000483:Alleles; D004303:Dosage Compensation, Genetic; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male