Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis.
Fragile sites are chemically induced nonstaining gaps in chromosomes. Different fragile sites vary in frequency in the population and in the chemistry of their induction. DNA sequences encompassing and including the rare, autosomal, folate-sensitive fragile site, FRA16A, were isolated by positional cloning. The molecular basis of FRA16A was found to be expansion of a normally polymorphic p(CCG)n repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The FRA16A locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis.
Nancarrow
J K
JK
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia.
Kremer
E
E
Holman
K
K
Eyre
H
H
Doggett
N A
NA
Le Paslier
D
D
Callen
D F
DF
Sutherland
G R
GR
Richards
R I
RI
D000483:Alleles; D001483:Base Sequence; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D018244:Chromosomes, Artificial, Yeast; D002885:Chromosomes, Human, Pair 16; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics; D006801:Humans; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide