title: Fine linkage and physical mapping suggests cross-over suppression with a retroposon insertion at the npc1 mutation.
abstract: Mouse Niemann-Pick disease type C1 (npc1), formerly designated spm (sphingomyelinosis), is an autosomal recessive lipid storage disorder. We generated a high-resolution linkage map in the 2.24-cM npc1 critical region by typing eight polymorphic markers in 2322 meioses (948 of these were previously reported). A minimal set of overlapping yeast artificial chromosomes (YACs) had previously been assembled (Hsu and Erickson 2000). The YAC 313-B-8, which 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 characterized, from the YAC-derived cosmids. The most proximal cosmid contig overlaps with markers near twirler (Tw). Both the physical map and genetic linkage map have been integrated to study the recombination frequencies in this particular region of the mouse genome, and recombination suppression due to the heterozygous insertion of DNA was suggested.
authors.affiliation: Angel Charity for Children-Wings for Genetic Research, Steele Memorial Children's Research Center, Department of Pediatrics, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hsu
authors.forename: R P
authors.initials: RP
authors.lastname: Erickson
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W S
authors.initials: WS
authors.lastname: Garver
authors.forename: R A
authors.initials: RA
authors.lastname: Heidenreich
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D020451:Contig Mapping; D003360:Cosmids; D018900:Dinucleotide Repeats; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018895:Microsatellite Repeats; D016254:Mutagenesis, Insertional; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*; D018626:Retroelements; D016324:Sequence Tagged Sites
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D018626:Retroelements