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You searched for +publisher:"Penn State University" +contributor:("Santhosh Girirajan, Committee Chair/Co-Chair"). Showing records 1 – 2 of 2 total matches.

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Penn State University

1. Raygoza Garay, Juan Antonio. Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection.

Degree: 2016, Penn State University

Antibiotics have had an enormous contribution to the improvement of human health, even beyond the realm of infection treatments. The discovery of many classes of antibiotics seemed to put an end to human infection and protect us indefinitely from our microbial enemies. However, we have come to realize that our enemies are entities subject to evolution and selection as all living systems on earth have been since the appearance of life. This strong selection for resistant bacteria has resulted in the diminished efficacy of antibiotics. Added to this is the high cost of screening new compounds that are safe and effective for their use in humans. Despite over a little more than a century of microbiology, bacteria keep surprising us with the myriad of mechanisms that they have acquired throughout the ages to adapt to a constantly changing environment. In this work, we present evidence for the first time that a genetic switch that is capable of increasing the mutation rate of the host bacterium was responsible for treatment failure in a case of Staphylococcus aureus infection. We show that this is the case by fully sequencing blood isolates taken from the patient. This sequencing revealed an evolution pattern consistent with a hypermutator infection. We also measure the mutation rate increase that this switch imparts onto its containing bacterium. We define a statistical model to differentiate mutator/non-mutator bacteria based on the results of whole genome sequencing. Finally, we measure the switching rate of the genetic element responsible for the increase in the mutation rate. Despite previous evaluation of the potential for this type of infection to happen, we present the first case to date to occur in a living host. With this, we hope to increase interest and awareness into understanding the frequency with which the failure of treatment might be linked to these kind of genetic switches. Advisors/Committee Members: Santhosh Girirajan, Dissertation Advisor/Co-Advisor, Santhosh Girirajan, Committee Chair/Co-Chair, itsvan albert, Committee Member, Andrew Read, Committee Member, Jason Rasgon, Outside Member.

Subjects/Keywords: Staphylococcus aureus; MRSA; Mutation rate; Phase variation; Genetic switch; Antibiotic Resistance; Vancomycin; endocarditis; microbiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Raygoza Garay, J. A. (2016). Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13611jzr186

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Raygoza Garay, Juan Antonio. “Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection.” 2016. Thesis, Penn State University. Accessed April 12, 2021. https://submit-etda.libraries.psu.edu/catalog/13611jzr186.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Raygoza Garay, Juan Antonio. “Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection.” 2016. Web. 12 Apr 2021.

Vancouver:

Raygoza Garay JA. Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Apr 12]. Available from: https://submit-etda.libraries.psu.edu/catalog/13611jzr186.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Raygoza Garay JA. Understanding the Role of a Hypermutator Switch in the Evolution of an Extremely Resistant Staphylococcus aureus Infection. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13611jzr186

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

2. Hall, Molly Ann. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.

Degree: 2015, Penn State University

Genome-wide association studies (GWAS) have identified numerous loci associated with human phenotypes. This approach, however, does not consider the richly diverse and complex environment with which humans interact throughout the life course, nor does it allow for interrelationships among genetic loci and across traits. Methods that embrace pleiotropy (the effect of one locus on more than one trait), gene-environment (GxE) and gene-gene (GxG) interactions will further unveil the impact of alterations in biological pathways and identify genes that are only involved with disease in the context of the environment. This valuable information can be used to assess personal risk and choose the most appropriate medical interventions based on an individual’s genotype and environment. Additionally, a richer picture of the genetic and environmental aspects that impact complex disease will inform environmental regulations to protect vulnerable populations. Three key limitations of GWAS lead to an inability to robustly model trait prediction in a manner that reflects biological complexity: 1) GWAS explore traits in isolation, one phenotype at a time, preventing investigators from uncovering relationships that exist among multiple traits; 2) GWAS do not account for the exposome; rather, they simply explore the effect of genetic loci on an outcome; and 3) GWAS do not allow for interactions between genetic loci, despite the complexity that exists in biology. The aims described in this dissertation address these limitations. Methods employed in each aim have the potential to: uncover genetic interactions, unveil complex biology behind phenotype networks, inform public policy decisions concerning environmental exposures, and ultimately assess individual disease-risk. Advisors/Committee Members: Marylyn Deriggi Ritchie, Dissertation Advisor/Co-Advisor, Marylyn Deriggi Ritchie, Committee Chair/Co-Chair, Santhosh Girirajan, Committee Chair/Co-Chair, Scott Brian Selleck, Committee Member, Ross Cameron Hardison, Committee Member, George H Perry, Committee Member, Catherine Mc Carty, Special Member.

Subjects/Keywords: gene-gene interactions; epistasis; PheWAS; phenome; EWAS; exposome; gene-environment interactions; complex traits

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hall, M. A. (2015). Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26751

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Hall, Molly Ann. “Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.” 2015. Thesis, Penn State University. Accessed April 12, 2021. https://submit-etda.libraries.psu.edu/catalog/26751.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Hall, Molly Ann. “Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.” 2015. Web. 12 Apr 2021.

Vancouver:

Hall MA. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 12]. Available from: https://submit-etda.libraries.psu.edu/catalog/26751.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hall MA. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26751

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.