Fetal branching determines final nephron number. Mild nephron deficit causes hypertension in "normal" adults. Thus, mechanisms that control branching are important. PAX2 and retinoic acid (RA) have profound effects on final nephron number, although the mechanism remains unknown. / We hypothesised that common variations in PAX2 cause subtle reduction in nephrons. We associated haplotype tagging single nucleotide polymorphisms (htSNPs) in PAX2 with a reduction in kidney mass in "normal" newborns and identified a haplotype on which an ancestral polymorphism is presumed to lie. We identified a SNP in linkage disequilibrium with this haplotype that caused alterations in PAX2 expression, linking reduction in expression with reduced nephrons. / We hypothesized that Lgl1, a pulmonary branching morphogen, is stimulated by RA to affect renal branching. We characterized Lgl1 expression in the kidney and its response to RA. Finally, we showed that Lgl1+/- embryos have reduction in kidney branching, implicating Lgl1 in nephron formation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101738 |
| Date | January 2007 |
| Creators | Quinlan, Jacklyn. |
| 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 | Master of Science (Department of Human Genetics.) |
| Rights | © Jacklyn Quinlan, 2007, 2006 |
| Relation | alephsysno: 002585030, proquestno: AAIMR32854, Theses scanned by UMI/ProQuest. |
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