Physical and genetic mapping on mouse proximal chromosome 18

An 8-Mb yeast artificial chromosome (YAC) contig has been constructed spanning 9 cM on mouse proximal chromosome 18. The contig consists of 49 YAC clones that cover roughly 15% of the chromosome. The map was assembled based on the presence or absence of 38 DNA microsatellites, from proximal DI8Mit109 through distal D18Mit68. The physical order of those microsatellite STSs have been assigned. The locations of 21 known genes including markers near twirler (Tw) and the recently isolated Niemann-Pick type C1 (Npc1), formerly designated as spm (sphingomyelinosis), are delimited on this physical map. Mouse Niemann-Pick disease type C1 (Npc1) is an autosomal recessive lipid storage disorder. We generated a high resolution linkage map in the 2.24 cM Npc1 critical region by typing 8 polymorphic markers in 2322 meioses. A minimal set of overlapping yeast artificial chromosome (YACs) has been assembled. The YAC 313-B-8 which covers this whole region, has been used to construct a cosmid library. Three cosmid contigs were built and one of them contained the Npc1 locus. Two (CA)n microsatellites were identified and characterized from the YAC derived cosmids. The most proximal cosmid contig overlaps with the markers near twirler gene (Tw). These identified YACs and cosmid clones will be an important resource for mouse geneticists wishing to further characterize the Npc1 gene and identify Tw and other genes in this region. The physical map and genetic linkage map were integrated to study the recombination frequencies in this particular mouse genome region. On average, it showed a recombination ratio of cM/Mb > 1.1. However, there is no recombination in the 300 Kb Npc1 critical region. We believe that the 703 bp deletion and 824 bp insertion of nonhomologous sequences in the mutation of Npc1 inhibits the occurrence of recombination in the region. These results confirm previous studies showing that recombination in mice is sensitive to heterozygous deletions or insertions of DNA fragments.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Graduate College

Grantor dc:publisher

The University of Arizona.

Year dc:date.issued

1998

Author dc:creator

• Hsu, Ssucheng Jeff, 1964-

Advisor dc:contributor.advisor

• Erickson, Robert P.

• Biology, Molecular.
• Biology, Genetics.
• Biology, Zoology.

Statement dc:rights

• Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10150/282617

OAI identifier oai:identifier

oai:repository.arizona.edu:10150/282617