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Global Signatures of Selection in Humans
(2018-05-13)
This thesis studies the properties and prevalence of natural selection operating on our species on a global or genome-wide scale. It is still not known how negative selection against deleterious mutations operates genome-wide, ...
Probabilistic Models of Structure in Biological Sequences
(2018-09-25)
The machinery of life is encoded in biological polymers for which sequence, structure, and function are intimately connected. This dissertation presents new probabilistic models for uncovering these connections from ...
Investigating the Roles of IRF6 in Epithelial Maturation, Craniofacial Development, and Orofacial Cleft Pathogenesis
(2018-04-10)
Cleft lip and/or palates (CL/P) are common congenital malformations, and mutations in the transcription factor IRF6 are the most significant genetic contributors to cleft pathogenesis. IRF6 is a master regulator of epithelial ...
Base-Resolution and Single-Cell Analysis of Active DNA Demethylation Using Methylase-Assisted Bisulfite Sequencing
(2018-05-10)
In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine through ten-eleven translocation (TET) dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine ...
Leveraging Functional Annotations and Multiethnic Data to Improve Polygenic Risk Prediction
(2018-09-25)
Polygenic risk prediction is a widely-investigated topic because of its potential clinical application as well as its utility to have a better understanding of the genetic architecture of complex traits. Methods to perform ...
Genetic Basis of Natural Variation in Cellular Decision Making in Wild Yeasts
(2018-05-15)
In nature, microbes often need to decide which of many potential nutrients to consume. This decision-making process is complex, involving both intracellular constraints and the organism’s perception of the environment. ...
Intergenerational Transmission of Non-Germline RNAs in Caenorhabditis Elegans
(2018-05-13)
In the model organism Caenorhabditis elegans, double-stranded RNA (dsRNA) capable of silencing genes can be introduced anywhere in the animal and will subsequently travel throughout the body and enter most cells, including ...
Global post-transcriptional regulators in Pseudomonas aeruginosa
(2018-08-17)
Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen found ubiquitously in both natural and manmade environments. Central to its ability to grow in different environments is the organism’s coordinated ...
What’s Good for the Goose Is Good for the Gosling? Evolutionary Theory, Parent-Offspring Conflict and Genetic Disorders
(2018-04-24)
Conflict is ever present in nature, serving as an essential driver of adaptation. In this dissertation I examine both intra- and interpersonal conflicts as they occur at the genetic level. Specifically, what happens when, ...
The Design and Characterization of Bifunctional Degraders of TRIM24, a Novel Transcriptional Dependency in Hematologic Malignancies
(2018-04-24)
Transcriptional control is critical to the proper functioning of cells, their growth, differentiation, and survival. Because genomic and epigenomic alterations can deregulate transcription and promote an oncogenic state, ...