ORGANIZATION OF THE ABCR GENE - ANALYSIS OF PROMOTER AND SPLICE JUNCTION SEQUENCES

Mutations in the human ABCR gene have been associated with the autosom al recessive Stargardt disease (STGD), retinitis pigmentosa (RP19), an d cone-rod dystrophy (CRD) and have also been found in a fraction of a ge-related macular degeneration (AMD) patients. The ABCR gene is st me mber of the ATP-binding cassette (ABC) transporter superfamily and enc odes a rod photoreceptor-specific membrane protein. The cytogenetic lo cation of the ABCR gene was refined to 1p22.3-1p22.2. The intron/exon structure was determined for the ABCR gene from overlapping genomic cl ones. ABCR spans over 100 kb and comprises 50 exons. Intron/exon splic e site sequences are presented for all exons and analyzed for informat ion content (Ri). Nine splice site sequence variants found in STGD and AMD patients are evaluated as potential mutations. The localization o f splice sites reveals a high degree of conservation between other mem bers of the ABC1 subfamily, e.g. the mouse Abc1 gene. Analysis of the 870-bp 5' upstream of the transcription start sequence reveals multipl e putative photoreceptor-specific regulatory elements including a nove l retina-specific transcription factor binding site. These results wil l be useful in further mutational screening of the ABCR gene in variou s retinopathies and for determining the substrate and/or function of t his photoreceptor-specific ABC transporter. (C) 1998 Elsevier Science B.V. All rights reserved.