Fine linkage and physical mapping suggests cross-over suppression with a retroposon insertion at the npc1 mutation

Mouse Niemann-Pick disease type C1 (npc1), formerly designated spm (sphingo myelinosis), is an autosomal recessive lipid storage disorder. We generated a high-resolution linkage map in the 2.24-cM npc1 critical region by typin g eight polymorphic markers in 2322 meioses (948 of these were previously r eported). A minimal set of overlapping yeast artificial chromosomes (YACs) had previously been assembled (Hsu and Erickson 2000). The YAC 313-B-8, whi ch covered this whole region, has been used to construct cosmid libraries. Three cosmid contigs were built, and one of them contained the npc1 locus. Two (CA)(n) microsatellites were identified, and the one new one was charac terized, from the YAC-derived cosmids. The most proximal cosmid contig over laps with markers near twirler (Tw). Both the physical map and genetic link age map have been integrated to study the recombination frequencies in this particular region of the mouse genome, and recombination suppression due t o the heterozygous insertion of DNA was suggested.