Introduction: As a part of the Gene Regulators in Disease project (GRID), this study aims to create a novel high throughput method to discover the genetic effect on gene translation, taking advantage of the rationale that efficiently translated mRNAs associate with multiple ribosomes, while less active ones with fewer or none. / Methods: Lymphoblastoid cell lines (LCLs) from 44 HapMap European individuals were used for polyribosomal fractionation and establishing the sample bank for the future study. The fractionated mRNA samples of 10 out of the 44 individuals were run on an Illumina GoldenGate Beadarray to detect allelic imbalance (developed by the group of T.J. Hudson and T.M. Pastinen). / Results: This study established a high-quality RNA bank, including 1,100 RNA fraction samples. By the Illumina chip, translational imbalance was detected in 75 out of 1483 (5.06%) assays, and 63 out of269 (23.4%) genes. The translational effect was well replicable by the resequencing method. / Conclusion: This study found that genetic effect on gene translation is a common mechanism of expression regulation. Our best hit found in the integrin beta 1 binding protein 1 gene (ITGB1BP1 ) highlights the role of mRNA 3'UTR secondary structure in gene translation. / Keywords: Gene translation, High throughput genotyping, Human genetics, Polyribosome, RNA, Single nucleotide polymorphism
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.116089 |
| Date | January 2008 |
| Creators | Lu, Yang, 1972- |
| 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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 003164469, proquestno: AAIMR67031, Theses scanned by UMI/ProQuest. |
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