ABSTRACT
Fragile site (FRAXA) expression is generally induced in fewer than 50% of cells at metaphase by direct or indirect deprivation of deoxypyrimidine ribonucleoside triphosphates in cell culture media. Confirmation of Lubs’ initial observation did not occur for several years, until cytogeneticists discovered that induction of the required folate-deficient medium. Linkage analysis in the FRAXA region began in 1983 with the initial reports of a 6% recombination frequency between electrophoretic polymorphisms of glucoses-phosphate dehydrogenase (G6PD) and the fragile X syndrome. Armed with a panel of well-characterized somatic cell hybrids with breakpoints at the fragile site and a plethora of tightly linked DNA markers, several groups emerged in the early 1990s in a ‘race’ to clone the molecular lesion associated with the fragile X syndrome. Since the major malady in humans with fragile X syndrome is mental retardation, a particularly intriguing finding involves the subcellular location of FMRP in central neurons.
