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Date of Award

Spring 2025

Document Type

Masters Thesis

Department or Program Affiliation

Biology

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Pollard, Dan A.

Second Advisor

Dahlberg, Lina

Third Advisor

Schwarz, Dietmar, 1974-

Abstract

Genetic variation plays a fundamental role in shaping phenotypic diversity by influencing gene expression at multiple levels. While most studies focus on mRNA abundance, emerging evidence suggests that genetic variation can independently affect protein expression, highlighting the need to investigate post-transcriptional mechanisms. Using Saccharomyces cerevisiae as a model, this study explores how genetic variation affects protein expression during dynamic gene regulation in the yeast mating pheromone response pathway.

To map the genetic determinants of differential protein expression, we developed a high-resolution quantitative trait locus (QTL) mapping approach that integrates bulk segregant analysis (BSA) with fluorescence-activated cell sorting (FACS). Traditional QTL mapping methods often fail to pinpoint causal variants to the single-nucleotide level. To address this, we introduce a novel fine-mapping strategy that selects for recombinants with crossover events within the target QTL region, improving mapping resolution. Although fine-mapping has not yet been completed, substantial method development was accomplished to enable this next phase. We plan to investigate its role in regulating FIG1 protein expression by applying this method to a trans-acting QTL containing CAM1 and DIG1. Previous studies identified this locus as influencing pheromone-responsive gene expression, but the causal variants remain unknown. Our fine-mapping approach ultimately aims to enable precise localization of the SNPs responsible for differential protein expression, providing new insights into the genetic mechanisms governing protein-specific gene regulation.

Type

Text

Keywords

fine-mapping, SNP mapping, bulk segregant analysis, protein expression, yeast

Publisher

Western Washington University

OCLC Number

1523694215

Subject – LCSH

Saccharomyces cerevisiae; Genetic regulation; Gene expression; Genetic polymorphisms; Gene mapping

Format

application/pdf

Genre/Form

masters theses

Language

English

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

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