THE GENES FOR X-LINKED OCULAR ALBINISM (OA1) AND MICROPHTHALMIA WITH LINEAR SKIN DEFECTS (MLS) - CLONING AND CHARACTERIZATION OF THE CRITICAL REGIONS

We have used cell lines from patients with deletions and translocation s involving the Xp22 region to map the genes for two X-linked disorder s, ocular albinism type 1 (OA1) and microphthalmia with linear skin de fects (MLS). Using existing and newly isolated DNA markers, the map po sition within Xp22 of key patient breakpoints, defining the boundaries of the genomic regions involved in these disorders (the critical regi ons), has been precisely determined. A 2.6 Mb yeast artificial chromos ome (YAC) contig, spanning the critical regions for these two disorder s, was assembled. Detailed long-range restriction analysis of the cont ig established the sizes of the critical regions to be 200 kb for OA1 and 800 - 925 kb for MLS. Ten potential CpG-islands, representing cand idate sites for genes, have been mapped within the 2.6 Mb region. Our data should greatly facilitate efforts aimed at cloning the genes for these developmental defects.