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Genetics Of Hippocampal Subregions Across Development, Jacob Pine
Genetics Of Hippocampal Subregions Across Development, Jacob Pine
Arts & Sciences Electronic Theses and Dissertations
Behavioral genetic analyses have not demonstrated robust, unique, genetic correlates of hippocampal subregion volume. The following study is the first population-based investigation of a) hippocampal longitudinal axis genetic factors b) hippocampal transverse axis genetic factors using both T1 and T2 MRI images and c) differences in the genetic components of hippocampal volume between post-adolescent adults and pre-adolescent children. Twin-based biometric analyses demonstrated that longitudinal axis subregions are associated with significant, unique, genetic variance, and that longitudinal axis subregions that are closer to one another are more genetically related than those further to one another. Although our analyses find that certain …
The Role Of Subclonal Gene Mutations During Progression From Myelodysplastic Syndrome To Secondary Acute Myeloid Leukemia, Andrew John Menssen
The Role Of Subclonal Gene Mutations During Progression From Myelodysplastic Syndrome To Secondary Acute Myeloid Leukemia, Andrew John Menssen
Arts & Sciences Electronic Theses and Dissertations
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis. Approximately 30% of MDS patients progress to secondary acute myeloid leukemia (AML). MDS is caused by somatic mutations in hematopoietic stem/progenitor cells and progression to secondary AML is associated with the acquisition and/or expansion of at least one subclone. We hypothesized that specific gene mutations would be enriched in subclones compared to founding clones, and that the order of mutation acquisition would be critical for clonal evolution and progression from MDS to secondary AML. Sequencing of paired MDS and secondary AML samples from 44 …
Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes
Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes
Arts & Sciences Electronic Theses and Dissertations
Pediatric musculoskeletal disorders are an extremely broad category of diseases that are often inherited. While individually rare, collectively these disorders are common, affecting around 3% of live births in the US. Despite the mounting clinical and molecular evidence for a genetic etiology, the cause for many patients with pediatric musculoskeletal disorders remain largely unknown. Major challenges in rare pediatric diseases include recruiting large numbers of patients and determining the significance and functional impacts of variants associated with disease within individuals or families. Whole exome sequencing (WES) is a powerful tool to identify coding variants that are associated with rare pediatric …
Refining The Characterization Of Causation In Early Childhood Neuropsychiatric Conditions: Nature, Nurture, And Time, Rachael Elizabeth Wagner
Refining The Characterization Of Causation In Early Childhood Neuropsychiatric Conditions: Nature, Nurture, And Time, Rachael Elizabeth Wagner
Arts & Sciences Electronic Theses and Dissertations
Understanding causal factors in the development of early childhood neuropsychiatric conditions is essential for an understanding of disease mechanisms and therapeutic approaches. Yet the lack of objective classification of psychiatric diagnoses, phenotypic and genetic heterogeneity, pleiotropy, and extensive comorbidity have posed immense challenges to the acquisition of knowledge regarding neuropsychiatric disease etiology. While it is unequivocally established that nearly all psychiatric conditions are substantially heritable, non-genetic factors do play a role in the development of psychopathology. This thesis explores both genetic and environmental contributors to neuropsychiatric conditions in an attempt to refine the characterization of some of these risk factors. …
Investigating The Role Of Genetic Variants And Environmental Factors In The Trajectory Of Substance Use Disorders, Linda Johnson
Investigating The Role Of Genetic Variants And Environmental Factors In The Trajectory Of Substance Use Disorders, Linda Johnson
Arts & Sciences Electronic Theses and Dissertations
Substance use disorders are a serious threat to public health with devastating social, economic, and health impacts on affected individuals and their families. This dissertation aims to improve understanding of substance use disorders in three parts: first, an epidemiological project examining smoking cessation and e-cigarette use at a population level; second, a genetic project examining the role of genetic variants on tobacco, alcohol, cannabis, and cocaine use; and finally, a review of the utility of polygenic risk scores in predicting risk of substance use behaviors. Cigarette smoking is a leading cause of preventable death, accounting for over 480,000 deaths in …
Genetic Factors That Contribute To The Pathogenesis Of Amyotrophic Lateral Sclerosis, Janet Elizabeth Cady
Genetic Factors That Contribute To The Pathogenesis Of Amyotrophic Lateral Sclerosis, Janet Elizabeth Cady
Arts & Sciences Electronic Theses and Dissertations
Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease for which there is no cure. The only treatment available extends survival by only a matter of months. There are over 20 genes that are known to cause ALS. Over half of the ALS cases with a family history of disease (FALS) can be explained by mutations in known ALS genes with hexanucleotide repeat expansions in C9ORF72 accounting for 40% of families. However roughly 90% of cases have no family history of disease (sporadic ALS or SALS) and a much smaller proportion (10%) of these cases can be explained by mutations in …
The Effects Of Hpa Axis Genetic Variation And Early Life Stress On Cortisol Levels In Preschool Age Children And On Amygdala And Hippocampus Volumes, Reactivity, And Connectivity At School Age, David Pagliaccio
Arts & Sciences Electronic Theses and Dissertations
Internalizing psychopathology has been linked to increased cortisol reactivity and alterations in limbic brain structure and function, yet the mechanisms underlying these alterations are unclear. One key hypothesis is that stress plays a major causal role in these mechanisms. Animal studies find that chronic stress or glucocorticoid administration lead to alterations in hippocampal and amygdala structure and function. Relatedly, life stress is a major risk factors for depression while candidate gene studies have related variation in hypothalamic-pituitary-adrenal (HPA) axis genes to increased prevalence and severity of depression. The present work tested the hypothesis that genetic profile scores combining variance across …