The goal of this thesis was to identify genetic loci involved in radiation-induced lung disease in mice. Phenotypic analysis was completed for alveolitis, pulmonary fibrosis, survival time, mast cells/mm2 and cell counts in bronchoalveolar lavage (BAL) to assess lung damage. Genome scans and linkage analysis were completed for two backcross cohorts (75%C3H/HeJ-25%C57Bl/6J or 25%C3H/HeJ-75%C57BU6J) using each of the phenotypes measured. Putative susceptibility loci were identified for alveolitis on chromosomes 12 (LOD=3.35), 14 (LOD=2.22) and 19 (LOD=1.7) in the mostly C3H/HeJ backcross cohort and on chromosome 14 (LOD=2.7) in the mostly C57BI/6J backcross cohort. Linkage using the pulmonary fibrosis scores provided supportive evidence for a quantitative trait loci (QTL) on chromosome 17 (LOD=2) in the mostly C57BI/6J background, and two unique putative linkage regions were localized on chromosome 2 (LOD=2.2) in the mostly C3H/HeJ cohort and 14 (LOD=2) in the mostly C57BI/6J cohort. Supporting evidence for linkage on chromosomes 12 and 14 in the mostly C3H/HeJ background and chromosome 14 in the mostly C57BI/6J background was obtained using cellular markers. Additionally, survival time mapped to the linkage regions isolated for alveolitis and pulmonary fibrosis, suggesting that the development of radiation-induced lung disease influences the survival time of the mice. Within each cohort there were sex dependent linkage intervals, indicating that male and female mice may possess different factors involved in the development of alveolitis and/or pulmonary fibrosis. These results suggest that there are multiple genetic loci involved in the development of radiation-induced lung disease in mice.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.99321 |
| Date | January 2006 |
| Creators | Bégin, Michelle Anne. |
| 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 | © Michelle Anne Bégin, 2006 |
| Relation | alephsysno: 002562311, proquestno: AAIMR28466, Theses scanned by UMI/ProQuest. |
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