Triplet (CGG)
expansion at the FMR-1 locus: Fragile-X Syndrome
At the FMR-1 locus on the X chromosome, most
individuals have from 6 ~ 54 copies of a CGG repeat. Slipped-mismatch repair
in the female germline gradually increases the number of
CGG repeats in some families. Normally-transmitting
males & their daughters are phenotypically unaffected.
In these daughters, unequal crossing-over between
X chromosomes with a high CGG copy number
further increases the copy number. At a threshold of ~200
copies, affected offspring will show the Fragile-X Syndrome
of mental retardation. The phenotype is less common in
females, where the alternative X chromosome with a low
number of CGG copies masks expression.
The repeat region creates a "satellite"
at the end of the long arm of the X-chromosome
that is subject to breakage, and which is cytologically
detectable as a "fragile
X" chromosome.