A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1

Abstract

Best's vitelliform macular dystrophy is an autosomal dominant disorder of unknown causes. To identify the underlying gene defect the disease locus has been mapped to an approximately 1.4-Mb region on chromosome 11q12-q13.1. As a prerequisite for its positional cloning we have assembled a high coverage PAC contig of the candidate region. Here, we report the construction of a primary transcript map that places a total of 19 genes within the Best's disease region. This includes 14 transcripts of as yet unknown function obtained by EST mapping and/or cDNA selection and five genes mapped previously to the interval (CD5, PGA, DDB1, FEN1, and FTH1). Northern blot analyses were performed to determine the expression profiles in various human tissues. At least three genes appear to be good candidates for Best's disease based on their abundant expression in retina or retinal pigment epithelium. Additional information on the functional properties of these genes, as well as mutation analyses in Best's disease patients, have to await their further characterization. [The GenBank/EMBL accession numbers and details of the isolation, localization, and characterization of ESTs and selected cDNAs are available as online supplements in Online Tables 1-3 at http://www.genome.org.]

Figure 1

Schematic representation of the physical and transcript map of the Best’s disease locus. (A) Two nonoverlapping YAC contigs extending the Best’s disease region proximally and distally. The order and location of genes and anonymous DNA markers were determined by STS content mapping. (B) The minimal Best’s disease interval between DNA markers at D11S1765 and UGB. The physical size of the region and the position of known genes and STSs is shown. (C) A selected set of overlapping PAC clones (Cooper et al. 1997) covering ∼1 Mb of genomic DNA of the candidate region was used to localize 17 distinct transcription units (TUs). Bold bars indicate PAC clone DNAs used for cDNA selection. (D) Regional assignment of 17 distinct TUs. The transcript sizes obtained by Northern blot analysis are in parentheses.

Figure 2

Northern blot analyses of cDNA fragments corresponding to the (TUs) as indicated (see Fig. 1). Examples are given to demonstrate the various expression profiles in lung (lane 1), cerebellum (lane 2), retina (lane 3), retinal pigment epithelium cell line ARPE-19 (lane 4), and heart (lane 5), brain (lane 6), placenta (lane 7), liver (lane 8), skeletal muscle (lane 9), kidney (lane 10), and pancreas (lane 11). The transcript sizes are indicated at left in kilobases.