title: Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.
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.
authors.affiliation: Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: M
authors.initials: M
authors.lastname: Pieretti
authors.forename: J S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Y H
authors.initials: YH
authors.lastname: Fu
authors.forename: D P
authors.initials: DP
authors.lastname: Kuhl
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: O
authors.initials: O
authors.lastname: Reiner
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.forename: M F
authors.initials: MF
authors.lastname: Victoria
authors.forename: F P
authors.initials: FP
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D003360:Cosmids; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D015723:Gene Library; D015321:Gene Rearrangement; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D016601:RNA-Binding Proteins; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D012313:RNA; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human