This thesis includes three studies examining the role of the type I (NPT1) and type II (NPT2) renal sodium (Na+)-phosphate (Pi) cotransporter genes in inherited hypophosphatemias. In the first study, the chromosomal locations of the NPT1 and NPT2 genes in human and rabbit are determined by physical mapping techniques. The NPT1 and NPT2 genes map respectively to human chromosomes 6p22 and 5q35 and to rabbit chromosomes 12p11 and 3p11. The localization of the two cotransporter genes to autosomes excludes them as candidate genes for X-linked hypophosphatemia. In addition, these assignments agree with the previously reported homology between rabbit chromosome 12 and human chromosome 6 and provide the basis for the establishment of a conserved syntenic group between rabbit chromosome 3 and human chromosome 5. / The goal of the second study was to clone, sequence and characterize the structure of the human NPT2 gene in order to design intronic primers to amplify NPT2 exons from patient DNA. Parallel experiments were performed on the mouse Npt2 gene, so that a vector could be designed to knockout the mouse Npt2 gene. In both species, the type II renal Na+-Pi cotransporter gene is approximately 16kb in length and is comprised of 13 exons and 12 introns. This work provides a basis for the study of the regulation of NPT2 transcription and facilitates the screening of DNA samples from patients with autosomally inherited disorders of renal Pi reabsorption for mutations in the NPT2 gene. / In the third study, polymorphic markers flanking the NPT1 and NPT2 genes were typed in members of a Bedouin kindred segregating the autosomal disorder Hereditary hypophosphatemic rickets with hypercaloiuria (HHRH). Genotype data were examined for excess homozygosity and allele sharing among affected pedigree members. Data did not reveal excess allele sharing on either chromosome 6 or 5, where the NPT1 and NPT2 genes are located, but suggested chromosome 3p as a site for further investigation. Identification of a HHRH locus is the first step toward identifying a gene involved in the pathophysiology of this disorder.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34987 |
| Date | January 1998 |
| Creators | Kos, Claudine H. |
| Contributors | Tenenhouse, H. S. (advisor), Morgan, K. (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 Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001641740, proquestno: NQ44478, Theses scanned by UMI/ProQuest. |
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