Browsing Genetics by Title
Now showing items 12-31 of 146
-
Biological and Clinical Consequences of a de novo Mutation in Glutaminase
The causes of bipolar disorder have been a mystery for as long as people have been writing about mental illness. Bipolar disorder is clearly familial but is not inherited in a simple way. Genetic studies have implicated ... -
Building multiplexed genomic tools for editing and interpreting human variation
Advances in DNA sequencing over the past twenty years have led to an unprecedented expansion in our ability to read DNA sequences and find genetic variation in individuals. However, our ability to manipulate and interpret ... -
Causes and consequences of genetic variation in budding yeast
The complex evolutionary forces that shape genomes result in sequences that are part utility and part history. The randomness involved in this process makes it difficult to imagine ever being able to read a genome and ... -
Certain observations concerning the effects of epistasis on complex traits and the evolution of genomes.
The informational content of genomes is usually interpreted as a sum of one-to-one relationships between nucleotides at certain genomic positions and phenotypic outcomes. While such interpretations have the virtue of ... -
Chromatin Deregulation in Cancer
During cancer development, committed cells are reprogrammed to malignant cell states. Genetic and epigenetic changes to chromatin complexes contribute to the reprogramming by disrupting normal cell identity and activating ... -
Comprehensively mapping the effects of mutations to influenza virus
Influenza virus is a rapidly evolving threat to public health. Influenza evolves through point mutations, so knowing the effects of all amino-acid mutations on the ability of the virus to withstand various selective pressures ... -
Conflict and Coevolution Shape the Primate Kinetochore
(2013-04-17)Centromeres and the kinetochore proteins that bind them are required for chromosome segregation during every eukaryotic cell division. Despite this conserved function, ongoing conflict between selfish centromeric DNA and ... -
CRISPR-based functional genomics to study gene regulatory architecture and consequences of genetic variation
If we divide the human genome into its noncoding and coding parts, the noncoding portion takes up ~98-99% of the genome, and the coding portion takes up ~1-2% (ENCODE Project Consortium, 2012). The coding portion of the ... -
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 ...