Mouse genome mapping is an essential integrating part of the human genome project because mouse has long been a valuable animal model for the investigate human genetic diseases. However, application of fluorescence in situ hybridization (FISH) in mouse has been hindered by technical difficulties related to the characteristics of mouse cytogenetics. To implement FISH as a tool for the mouse genome project, we developed high-resolution FISH and applied it to mouse and comparative genetics. / Using an original technique, we obtained high-resolution replication R-banded mouse chromosomes (over 500 bands per haploid). We constructed a new high-resolution R-banding idiogram, for an easier identification of mouse chromosomes allowing mouse gene mapping with greater precision. / Two mouse renal Na-Pi cotransporter genes (Npt1 and Npt2) were assigned to mouse chromosome region 13A3-A4 and 13B respectively. The autosomal localization excluded Npt1 and Npt2 as direct disease genes for X-linked hypophosphatemia and implicated them as candidate genes for autosomally inherited hypophosphatemia, hereditary hypophosphatemic rickets with hypercalciuria and hypophosphatemic bone disease. This study demonstrated that gene mapping using FISH is a direct approach in linking genetic diseases and relevant function genes. / In order to directly generate information transferable from mouse to human, we conducted comparative gene mapping study by FISH. Human HLCS, mapped to human chromosome 21q22.1, was assigned to mouse chromosome region 16C4 with a human probe. Conversely, mouse Mborg-1 gene, localized to mouse chromosomes 2H1, was mapped to human chromosomes 20q13 with the murine probe. Moreover, two clusters of mouse gene/DNA marker in the region of Bcg and Lp locus at mouse chromosome 1C4, 1H1 respectively were cross-mapped to human chromosomes 2q35 and 2q23 respectively. The results yields higher resolution than linkage studies and thus allowed us to narrow down the chromosomal region containing the human homologues, as a first step for the cloning of the human genes. / In an attempt to positionally clone the Lp gene, we established for the first time a linear relationship between optical distance in interphase nuclei and physical distance between DNA sequences, ranging from 130kb to 1500kb, using two-color FISH. The relative position and genomic distance between four markers flanking Lp locus was effectively estimated.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34688 |
| Date | January 1997 |
| Creators | Zhang, Xiao-Xiang. |
| Contributors | Eydoux, Patrice (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001601786, proquestno: NQ37034, Theses scanned by UMI/ProQuest. |
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