Physical mapping of Xp11.22-Xp11.3; an interval containing the RP2 gene
- Institute of Ophthalmology, London (United Kingdom); and others
Genetic linkage studies have established a region on the short arm of the human X chromosome (Xp11.22-Xp11.3) to be implicated in several inherited opthalmic diseases. Aland Island eye disease (AIED), congenital stationary night blindness 1 (CSNB1), X-linked progressive cone dystrophy and one form of retinitis pigmentosa (RP2) all map to the interval. A lack of multiple informative recombinants in RP2 families, coupled with the paucity of highly polymorphic markers in this region, has to date impeded progress in refining the genetic interval containing this gene. A YAC contig is being generated as a total for the isolation of microsatellites and candidate genes in the region of interest. This contig will be constructed to cover and extend beyond the two markers flanking this interval, MAO (Xp11.3) and DXS255 (Xp11.22), a genetic distance of approximately 9 cM. Since the best evidence for linkage to RP2 is with the markers DXS255 and DXS426 (Xp11.23), these were used to initiate the construction of a contig utilizing a PCR-based screening strategy on the ICI 4X YAC library. Other STSs derived from genes and known microsatellite markers in the region were likewise used to obtain seed YACs within this interval. End sequences from such YACs have been obtained by a combination of Alu-vector PCR and chemical genetics methodologies to generate novel STSs with which to isolate overlapping clones. A complete contig is now assembled from TIMP to DXS1126, encompassing a physical distance of approximately 2-3 Mb. Microsatellite markers are being isolated from YACs which appear to span critical cross-overs in affected RP2 patients. In this way we hope to refine the localization of the RP2 gene. Key YACs will then be analyzed for CpG islands and retinally expressed sequences which may become candidate genes for the several opthalmic diseases mapping to Xp11.
- OSTI ID:
- 134484
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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