Large-scale analysis of sequence tags in Xp11.4-11.3 and evaluation of candidate genes for X-linked ocular diseases.

The gene-rich region of Xp11.4-Xp11.3 was characterized by increasing the physical marker density. Sequence tags (STSs) were generated by IRS- and DOP-PCR techniques, subsequent cloning, sequencing, and creation of primer pairs for single-copy sites. A total of 224 novel STSs were collected, providing an average marker density of 18 kb in the Xp11.4-Xp11.3 region which is assumed to be approximately 4 Mb in size. Sequence analysis of generated and established STSs via data base searches identified a novel gene highly homologous with the protein phosphatase 1 inhibitor 2 (IPP-2) and two pseudogenes; all of which map to the approximately 1.5 Mb proximal region of the critical region for X-linked congenital stationary night blindness type I (CSNB1) between markers DXS993 and DXS228. Using well-defined DNA panels, 69 STSs were fine-mapped to this approximately 1.5 Mb region, providing a marker coverage of one marker per 22 kb. No allelic loss was observed when the total STS content was applied to patient DNAs by PCR-mediated amplification. However, given the association of this region with a number of inherited ocular diseases, the data presented here provide valuable tools for genetic linkage and large-scale association studies.