Persistent Link:
http://hdl.handle.net/10150/282617
Title:
Physical and genetic mapping on mouse proximal chromosome 18
Author:
Hsu, Ssucheng Jeff, 1964-
Issue Date:
1998
Publisher:
The University of Arizona.
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.
Abstract:
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.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Genetics.; Biology, Zoology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Genetics
Degree Grantor:
University of Arizona
Advisor:
Erickson, Robert P.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titlePhysical and genetic mapping on mouse proximal chromosome 18en_US
dc.creatorHsu, Ssucheng Jeff, 1964-en_US
dc.contributor.authorHsu, Ssucheng Jeff, 1964-en_US
dc.date.issued1998en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © 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.en_US
dc.description.abstractAn 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.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Genetics.en_US
dc.subjectBiology, Zoology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineGeneticsen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorErickson, Robert P.en_US
dc.identifier.proquest9829354en_US
dc.identifier.bibrecord.b38553880en_US
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