Browsing Genetics by Title
Now showing items 20-39 of 146
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De novo missense mutations in neurodevelopmental disorders
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder (NDD) with a high prevalence in the US (1 in 59 children). It is commonly comorbid with other NDDs such as developmental delay (DD), intellectual ... -
Defining more rules of environmental and phenotypic buffering
Phenotypes and organisms are robust, or ‘buffered,’ and thus able to withstand environmental and mutagenic disturbances to maintain wild-type functions. However, the specific mechanisms that ensure phenotypic buffering, ... -
Developing Proteomic Methods to Assay Function of Proteoforms
The human genome encodes a repertoire of ~20,000 proteins. The unique functional roles of these proteins diversify through mechanisms of allelic variation, post-translational modifications (PTMs), alternative splicing, and ... -
Development and application of accurate mass measurements for large-scale protein interaction and proteome studies
(2013-07-25)Traditionally and most commonly, accurate mass measurement is utilized to restrict peptide candidate search space on the precursor level to impart greater specificity in large peptide sequence databases. While use of ... -
Development and application of combinatorial single cell methods to tissue physiology and disease
Advances in single-cell sequencing technologies present an opportunity to study the cellular and molecular basis of complex tissue physiology at global scale with unprecedented throughput. In this work, methods for application ... -
Development of amyloidosis typing method and data acquisition strategies using tandem mass spectrometry
A variety of mass spectrometry acquisition methods are designed to maximize multiplexing capacity, quantification accuracy, or detection sensitivity of peptide ions in complex biological matrices. Data-independent acquisition ... -
Development of an Allele-Aware Method to Study the Nuclear Organization of the FSHD Locus
(2012-09-13)The human genome carries out its functions, including the establishment and maintenance of tissue-specific gene expression programs, within the confines of the cell nucleus. The genome is not randomly organized within this ... -
Development of Data Independent Acquisition Methods to Systematically Analyze the Human Proteome
Data independent acquisition (DIA) mass spectrometry is a powerful technique that is improving the reproducibility and throughput of mass spectrometry-based proteomics studies. Here we explore several new approaches to ... -
Development of Data Independent Acquisition Techniques for the Analysis of Protein Mixtures by Tandem Mass Spectrometry
(2013-07-25)Novel algorithms and data acquisition methods designed to improve the ability to identify and quantify proteins in complex biological mixtures using tandem mass spectrometry are presented. An algorithm for de novo correction ... -
Directed evolution and de novo design for improved pathogen-targeting protein drugs
Infectious diseases continue to claim millions of lives, and protein design with Rosetta is quickly becoming a contributor to the fight against these diseases. My dissertation has focused on leveraging recently developed ... -
Discovery and characterization of genes responsible for inherited hearing loss
Hearing loss is the most common sensory dysfunction in humans, affecting 1 in 400 newborns and an estimated 27 million adults in the United States. Current treatments, such as hearing aids and cochlear implants, increase ... -
Divergent Single-Cell Trajectories in Homeostatic Control and Genome Instability during Aging
The budding yeast has a long and storied history as a model organism for biological inquiry. Accordingly, experiments into the replicative aging of S. cerevisiae have yielded critical insights into evolutionarily conserved ... -
THE EFFECTS OF ANEUPLOIDY ON CELLULAR FITNESS AND AGING
Aneuploidy plays an important role in myriad biological processes. In the case of multicellular organisms, germline and somatic aneuploidy, respectively, have been associated with atypical development and diseases such ... -
Efficiently searching for enhancers and their target genes in the human genome
A single 3 billion letter genome contains the instructions for the 37 trillion diverse cells that make up one human. To accomplish this, the ~21,000 human genes are expressed and perform function in highly specific ... -
Enabling Community-Driven Proteomics
As the field of proteomics matures, it faces several computational challenges. This dis- sertation describes three new computational methods to address some of these challenges: Metapeptides, Param-Medic and GLEAMS. ... -
Epigenetic Regulation of Pluripotent and Multipotent Stem Cell Systems
The epigenome defines what a cell has the potential to do and allows a cell to elicit a response to external cues. This is exemplified in organisms where all the hundreds of different cell types share one genome but differ ... -
Establishment of a Drosophila model of intestinal sterol absorption and trafficking
(2007)Despite diet being a major source of cholesterol in Western culture, the absorption and downstream trafficking of cholesterol remain poorly understood processes. In humans, proteins of the NPC1 family are essential for ... -
Evolution and diversity of hominid genomes
(2014-02-24)Copy number variants (CNVs) contribute to a substantial amount of diversity both between and among hominid species. In this thesis I set out to catalog this variation across the hominid lineage and assess its impact on the ... -
The evolution and function of regulatory regions in yeast
Gene regulatory changes have long been theorized to be a source of evolutionary novelty. In more recent years, we have learned that noncoding changes can have a large effect on phenotype and disease and can be of evolutionary ... -
Evolutionary analysis of viral sequences in eukaryotic genomes
The focus of this work is several evolutionary analyses of endogenous viral sequences in eukaryotic genomes. Endogenous viral sequences can provide key insights into the past forms and evolutionary history of viruses, as ...