Physical mapping of the albino-deletion complex in the mouse to localize alf/hsdr-1, a locus required for neonatal survival

The albino-deletion complex in the mouse defines a genetically well-characterized region of chromosome 7 in which a number of loci essential for normal development and viability reside. One locus, designated alf or hsdr-1, is necessary for neonatal survival. Its absence results in hypoglycemia associated with biochemical and ultrastructural abnormalities in hepatocytes and proximal tubule cells of the kidney. We constructed a long-range physical map of the region defined by the proximal segment of the albino-deletion complex as a step toward localizing alf/hsdr-1. Sixteen markers, including 11 whose isolation is described here and in the accompanying paper (A. Schedl et al., 1992, Genomics 14, 288-297), were ordered on a panel of albino-deletion DNAs and their distribution was examined by pulsed-field gel electrophoresis. The resulting approximately 4300-kb physical map covers the entire region absent from the prototypic alf/hsdr-1 deletion c14CoS, estimated as approximately 3600 kb. Since the deletion c11DSD complements and overlaps most of c14CoS, alf/hsdr-1 was mapped at the proximal extreme of c14CoS, approximately 3000 kb from the albino locus. The density of CpG islands was found to be very heterogeneous across the region mapped.