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Journal of Applied Genetics 42(1), 2001, pp. 89-102

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

Carsten M. PUSCH

Abstract: 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 ~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 ~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 ~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.

Key words: genetic diseases, human X-chromosome, IPP-2, night vision, physical map, polymerase chain reaction, pseudogene, sequence tags.

Correspondence: C.M. Pusch, Molekulargenetisches Labor, Universitnts-Augenklinik, Auf der Morgenstelle 15, 72076 Tubingen, Germany, e-mail: