A New DNA Marker Tightly Linked to the Fragile X Locus ( FRAXA )

Abstract

The fragile X syndrome is the most common cause of familial mental retardation. Genetic counseling and gene isolation are hampered by a lack of DNA markers close to the disease locus. Two somatic cell hybrids that each contain a human X chromosome with a breakpoint close to the fragile X locus have been characterized. A new DNA marker (DXS296) lies between the chromosome breakpoints and is the closest marker to the fragile X locus yet reported. The Hunter syndrome gene, which causes iduronate sulfatase deficiency, is located at the X chromosome breakpoint that is distal to this new marker, thus localizing the Hunter gene distal to the fragile X locus.

IDS gene-pseudogene exchange responsible for an intragenic deletion in a hunter patient

“…Pseudogene exons I1 and 111 hybridize both with the 7.5-kb EcoRI fragment and with the 2.7-kb and the 6.4-kb Hind111 fragments, respectively. 10, locus DXS 465 (Hulsebos et al, 1991); probe U6.2, locus DXS 304 (Dahl et al, 1989); probe VK21A, locus DXS 496 (Suthers et al, 1989); and specific exon probes obtained from pB2Sc17 by PCR with the following sets of primers: exon 11: EII.5' and EII.3' (135 bp); exon 111: EIII.5' and EIII.3' (115 bp). Microsatellite at locus DXS1113 was analyzed as described by Weber et al (1993).…”

New distal marker closely linked to the fragile X locus

“…Its 370-bp insert was recloned in pSP65 (Promega). Other probes used in this study were VK21A and VK21C, each identifying locus DXS296 (Suthers et al 1989), U6.2, identifying locus DXS304 (Vincent et al 1989), and F814, identifying locus DXS52 (Heilig et al 1988). Standard procedures were followed for the isolation of genomic DNAs, digestion with restriction enzymes, electrophoresis in agarose gels and Southern hybridization (see Sambrook et al 1989).…”

“…The human x hamster hybrid cell line 908K1B17 and the human x mouse hybrid cell lines LC12K15 and CY34, used for the regional localization of II-10, have been described in detail previously (Schonk et al 1989;Suthers et al 1989Suthers et al , 1990Schmidt et al 1990).…”

“…At present, the closest marker on the proximal side is DXS369 at 5% recombination ). On the distal side, two closely linked markers have been identified: DXS296 without recombination (Suthers et al 1989), and DXS304 at 2%-5% recombination (Vincent et al 1989). Although favourably located, DXS296 is of limited value for diagnostic application because of Offprint requests to: T. J. M. Hulsebos its low informativity.…”

Forty Years From Markers to Genes

“…Not known to us at the time, there were two more folate sensitive fragile sites close to FRAXA, namely FRAXE and FRAXF. Later we discovered that the human DNA fragment in Val Hyland's clone VK21 which was closely linked to FRAXA (Suthers et al, 1989), was in fact part of the FMR2 gene associated with FRAXE mental retardation (Gecz et al, 1996).…”