Introduction. Programmed Death 1 is a molecule that becomes expressed on the surface of B and T cells once they are activated. Binding with its ligands, PD-L1 and PD-L2 which are found on T cells, antigen-presenting cells and peripheral tissues, causes inhibition of the PD-1-bearing cell. Knockout of the PD-1 gene in mice causes autoimmune nephritis, arthritis and cardiomyopathy. A study in humans demonstrated that an intronic SNP, named PD-1.3, is associated with lupus in several different populations. Studies on whether this polymorphism affects gene expression proved inconclusive and its biologic significance remains unknown. / Methods. We began by sequencing the gene which led to the discovery of one previously unreported SNP. Using this and twenty-six publicly available SNPs, we genotyped ninety individuals. We measured total gene expression by real-time PCR on cDNA from EBV-immortalized B cells. We tested for allelic imbalance by fluorescence polarization. As a preliminary test for alternate splicing, PCR was done on cDNA using primers that covered the exons adjacent to PD-1.3. / Results. We found five polymorphic sites in significant linkage disequilibrium with PD-1.3. One of these SNPs, PD-1.4, had shown only weak association with lupus in the above-mentioned study and another of the five is in complete disequilibrium with PD-1.4. We demonstrated that PD-1.3 lies in a region of high linkage disequilibrium. None of the twenty-seven polymorphic sites, including PD-1.3, correlated with gene expression assayed by real-time PCR or allelic imbalance. We did not demonstrate an association between PD-1.3 and alternate splicing.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82299 |
| Date | January 2004 |
| Creators | Nashi, Emil |
| 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 | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198709, proquestno: AAIMR12510, Theses scanned by UMI/ProQuest. |
Page generated in 0.0981 seconds