Identification of a Gene (FMR-1) Containing a CGG Repeat Coincident With a Breakpoint Cluster Region Exhibiting Length Variation in Fragile X Syndrome

Cell. 1991 May 31;65(5):905-14. doi: 10.1016/0092-8674(91)90397-h.

Abstract

Fragile X syndrome is the most frequent form of inherited mental retardation and is associated with a fragile site at Xq27.3. We identified human YAC clones that span fragile X site-induced translocation breakpoints coincident with the fragile X site. A gene (FMR-1) was identified within a four cosmid contig of YAC DNA that expresses a 4.8 kb message in human brain. Within a 7.4 kb EcoRI genomic fragment, containing FMR-1 exonic sequences distal to a CpG island previously shown to be hypermethylated in fragile X patients, is a fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes. This fragment contains a lengthy CGG repeat that is 250 bp distal of the CpG island and maps within a FMR-1 exon. Localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Brain / metabolism
  • Cosmids
  • DNA / genetics
  • DNA / isolation & purification
  • Exons
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics*
  • Gene Library
  • Gene Rearrangement
  • Genetic Variation*
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Probes
  • Polymerase Chain Reaction / methods
  • RNA / genetics
  • RNA / isolation & purification
  • RNA-Binding Proteins*
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Restriction Mapping
  • Translocation, Genetic*
  • X Chromosome*

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • Oligonucleotide Probes
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • RNA
  • DNA

Associated data

  • GENBANK/M60958
  • GENBANK/M60959
  • GENBANK/M60960
  • GENBANK/M60961
  • GENBANK/M60962
  • GENBANK/M63447
  • GENBANK/M64383
  • GENBANK/M64384
  • GENBANK/M67468
  • GENBANK/M86183