Portland State University. Department of Biology
Kim H. Brown
Date of Award
Doctor of Philosophy (Ph.D.) in Biology
1 online resource (x, 133 pages)
No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)--large (>1 Kb) duplications or deletions across the genome--on the toxicant-susceptibility phenotype.
Herein I have characterized copy number variants across three commonly used laboratory strains of zebrafish (Danio rerio) and identified mRNA expression phenotypes in the same strains. I found that males and females have only a 14% overlap in differentially expressed mRNA transcripts across three common laboratory strains, congruent with the growing body of work identifying sex- and strain-specific phenotypes in zebrafish. Furthermore, I identified two strain-specific response quantitative trait loci (QTL) that explain about a third of the variation in susceptibility to PCB and tested the response QTL using targeted CRISPR-Cas9 editing of the CNV involved. Overall, this body of work defines CNV and mRNA expression variation across zebrafish strains, identifies CNV causal in the PCB-susceptibility phenotype, and confirms the PCB-susceptibility QTL using targeted genomic editing.
Holden, Lindsay Adrian, "Investigating the Role of Genomic Variation in Susceptibility to Environmental Chemicals across Populations" (2018). Dissertations and Theses. Paper 4371.
Available for download on Wednesday, May 15, 2019