Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.
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.
Verkerk
A J
AJ
Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands.
Pieretti
M
M
Sutcliffe
J S
JS
Fu
Y H
YH
Kuhl
D P
DP
Pizzuti
A
A
Reiner
O
O
Richards
S
S
Victoria
M F
MF
Zhang
F P
FP
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
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