Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Author ORCID Identifier
https://orcid.org/0000-0001-9701-2048
AccessType
Campus-Only Access for Five (5) Years
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Molecular and Cellular Biology
Year Degree Awarded
2021
Month Degree Awarded
September
First Advisor
John G. Gibbons
Subject Categories
Genetics | Genomics
Abstract
Aspergillus fumigatus is a potentially lethal opportunistic pathogen that causes ~600,000 deaths per year globally. In order to better prevent and treat A. fumigatus infections, it is critical to identify the genomic loci involved in the medically relevant traits. Previously, the molecular mechanisms underlying these traits are mostly investigated using hypothesis-driven gene candidate approach. However, although this approach has yield significant results, it is inherently biased and easily overlooks the genes that are seemingly irrelevant. Here, we used unbiased method, genome-wide association (GWA) analysis, to identify loci involved in azole (a class of antifungal drugs) sensitivity and thermotolerance by analyzing the association between over 100K SNPs and these two traits. We independently conducted GWA for these two traits and discovered a one-gene locus (Afu2g02220) associated with azole sensitivity and a three-gene locus (Afu3g15170, Afu3g15190 and Afu3g15200) associated with growth rate at 52°C, respectively. To functionally validate these two loci, we knocked them out using a CRISPR/Cas9 approach. The Afu2g02220 KO strains grow significantly slower than their parent strain with the presence of azole. Our results suggest that GWA paired with efficient gene deletion is a powerful and unbiased strategy for identifying the genetic basis of complex traits in A. fumigatus.
DOI
https://doi.org/10.7275/24598547
Recommended Citation
Zhao, Shu, "APPLYING GENOME-WIDE ASSOCIATION IN THE FUNGAL PATHOGEN ASPERGILLUS FUMIGATUS TO IDENTIFY THE GENETIC CONTRIBUTORS OF ANTIFUNGAL SENSITIVITY AND THERMOTOLERANCE" (2021). Doctoral Dissertations. 2392.
https://doi.org/10.7275/24598547
https://scholarworks.umass.edu/dissertations_2/2392