Genetics and Genomics Commons^™

The E2f4 Prognostic Signature Predicts Pathological Response To Neoadjuvant Chemotherapy In Breast Cancer Patients, Kenneth M. K. Mark, Frederick S. Varn, Matthew H. Ung, Feng Qian, Chao Cheng

Dartmouth Scholarship

Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in …

Genetic Metabolic Complementation Establishes A Requirement For Gdp-Fucose In Leishmania, Hongjie Guo, Natalia M. Novozhilova, Giulia Bandini, Salvatore J. Turco, Michael A. L. Ferguson, Stephen M. Beverley

Molecular and Cellular Biochemistry Faculty Publications

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Arap) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and …

Identification Of Intrahelical Bifurcated H‑Bonds As A New Type Of Gate In K+ Channels, Oliver Rauh, Martin Urban, Leonhard M. Henkes, Tobias Winterstein, Timo Greiner, James L. Van Etten, Anna Moroni, Stefan M. Kast, Gerhard Thiel, Indra Schroeder

James Van Etten Publications

Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K⁺ channels, Kcv_S and Kcv_NTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in Kcv_NTS and 40% in Kcv_S. …

Pathogenesis, Virulence And Population Genetics Of Puccinia Emaculata, The Causal Agent Of Switchgrass Rust, Qunkang Cheng

Doctoral Dissertations

The infection process of Puccinia emaculata on Panicum virgatum leaves was studied histologically. Appressoria were formed approximately 10 hr after inoculation and penetrations were observed over stomatal openings. Substomatal vesicles developed 3 days after inoculation (DAI) and at 5 DAI, both haustorial mother cells and haustoria were observed. At 11 DAI, uredinia were developing, but urediniospores were immature. Until 14 DAI, matured uredinia ruptured host epidermis and urediniospores were released for secondary infection. This clearly studied infection process will help understand resistance mechanisms of a resistant cultivar in future research.

Twelve agronomic and ornamental switchgrass cultivars were inoculated with 40 …

Systematics, Diversification, And Functional Diversity Of Russulaceae (Russulales), Brian Patrick Looney

Doctoral Dissertations

The family Russulaceae is an iconic family of mushroom-forming Basidiomycetes both because of their importance as edible mushrooms in many parts of the world and their species richness in both temperate and tropical forested biomes. While much mycological research has been focused on this group, recent systematic and ecological research has failed to develop a comprehensive or cohesive organization by which to understand the evolutionary relationships, patterns of diversification, or functional importance of the group. Recently, interest in ectomycorrhizal fungi (EmF), of which Russulaceae is a key lineage, has greatly increased due to the recognition of the importance of EmF …

Role Of Hormonal And Developmental Signaling In Plant-Cyst Nematode Interaction, Sarbottam Piya

Doctoral Dissertations

Plant-parasitic cyst nematodes are one of the most destructive root parasites that cause severe yield losses in many crop plants. These obligate parasites induce a specialized multi-nucleate feeding site called syncytium. This study was conducted to explore the roles of phytohormones particularly auxin and ethylene, and miRNA-mediated crosstalk between development and defense responses in establishing the compatible interaction between Arabidopsis and Heterodera schachtii. Using yeast two-hybrid assay, a complete protein-protein interaction map between Auxin/indole-3-acetic acid (Aux/IAA) proteins and auxin response factors (ARFs) was generated. In addition, gene co-expression profiles of ARFs and Aux/IAAs were incorporated with protein-protein interaction data. …

Ecological And Evolutionary Dynamics Of Plant-Soil Feedbacks: Influences On Evolution And Range Dynamics, Michael E. Van Nuland

Doctoral Dissertations

Plants interact with, modify, and are affected by their soil environments. Though plant-soil interactions are well known to be important and active regulators of ecosystem function and community structure, much less is known about how these interactions affect plant evolution. The primary goal of my dissertation was to examine plant-soil interactions under a range of ecological and evolutionary contexts to better understand patterns of biodiversity, ecosystem function, and whole system responses to environmental change. Taking such an eco-evolutionary perspective allows for a holistic understanding of the causes and consequences of complex abiotic and biotic interactions that link ecosystem ecology and …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Using Phylogenetic Comparative Methods To Understand Diversification And Geographic Range Evolution, Kathryn Aurora Massana

Doctoral Dissertations

Two key processes that have been modeled in a phylogenetic comparative framework are diversification and historical biogeography. Many questions arise on what process have shaped the abundance (or lack) of species we see today and what influences their survival and interconnectedness with other species. Many methods have been developed to answer these questions. Over the past several decades there has been a rise in parametric modeling and development of more adequate frameworks to answer biological questions of interest. However, many models still lack the incorporation of ecological, mainly biotic factors, which influence the evolution and ecology of species, while accounting …

The Psychosocial Effects Of Next Generation Sequence Panels For Predictive Testing Of Hereditary Dementias, Dina Green

Human Genetics Theses

The current standard of care in offering predictive genetic testing for neurodegenerative diseases is that individuals wishing to have testing must have a known family mutation or well-documented family history of a specific disease. This model denies testing to individuals in families where the phenotype of the disease is less clear. However, NGS panel testing for many genes with overlapping phenotypes helps alleviate both the cost and tedious nature of a genetic “fishing expedition.” Panel testing increases the risk of receiving variants of unknown significance and, therefore, uncertainty. The goal of this research study is to examine the psychological impact …

Genetic Counselors’ Assessment Of Videos To Augment Whole Exome Sequencing Patient Education, Rebecca Hernan

Human Genetics Theses

Patient education for basic genetics as well as genetic testing options is a key role of a genetic counselor (GC). As whole exome sequencing (WES) becomes more commonly used in clinical care, an increased burden of genetic education is placed on both the GC and the patient due to the complexity of this test. One method to help alleviate this burden is the use of educational tools, these tools need to be assessed for their efficacy. There is a lack of research eliciting GCs’ opinion of educational tools intended for WES. The parents of minor patients evaluated at Columbia University …

Knowledge And Attitudes After Using Videos To Educate A Non-Clinical Cohort About Prenatal Cell-Free Dna Screening, Teresa Cacchione, Safa Yusuf

Human Genetics Theses

Prenatal cell-free DNA (cfDNA) screening is now offered to pregnant women of all risk categories, creating a challenge in providing informed decision-making on a broad scale. Resources to support patient education, such as short educational videos, have been created to help ameliorate this issue but have not been formally evaluated. Thus, we sought to investigate the utility of videos in educating women about prenatal cfDNA screening and whether there were differences in knowledge and/or attitudes after viewing a video created by a non-profit genetics organization (Video A) versus a similar video created by a commercial testing company (Video B). Participants …

Adolescent Perspectives On Genetic Testing For Adult Onset Conditions, Olivia D’Accordo, Erin Davidson, Christina Miller, Yael Weinstein

Human Genetics Theses

The American Society of Human Genetics (ASHG) recommends that testing for adult onset conditions be deferred until adulthood because of the potential for psychological harm combined with lack of medical utility. ASHG’s 2016 DNA Day Essay Contest asked 9- 12th graders to defend or refute this position. 1241 essays were submitted. 572 students defended ASHG’s position statement, while 554 argued against. Essays that addressed Alzheimer’s disease (AD) and BRCA-related Hereditary Breast and Ovarian Cancer syndrome were qualitatively analyzed for themes related to the argued position. 64.4% of students argued for deferred testing of AD, and 46.1% of students argued for …

Dna Unicorn: An N-Of-1 Community Advocacy Resource, Allison Knickle, Taylor Laut, Kari Magnussen, Marianne Vivien

Human Genetics Theses

With the wider use of genetic testing, an increasing number of people are receiving molecular diagnoses of ultra-rare or N-of-1 diseases. The medical and psychosocial challenges of these individuals are compounded by a lack of support and advice from disease-specific communities. A website ( www.dnaunicorn.org) was developed to help N-of-1 families connect with caregivers, researchers, and patients with the same or related medical conditions. The site provides directions and links to resources to facilitate data-sharing through access to databases, and aids in the construction of social media campaigns to connect genotypically- or phenotypically-related patients and families to each other. Furthermore, …

A Retrospective Chart Review Examining The Clinical Utility Of Family Health History, Katherine Dao, Julia Russo

Human Genetics Theses

Family health history (FHH) is a simple and cost-effective clinical tool widely used by genetic professionals. Although the value of FHH for assessing personal and familial health and reproductive risk within a prenatal population has been demonstrated in past studies, its utility within a genetic carrier screening population has not been evaluated. The purpose of this study was to examine the utility of FHH as a clinical screening tool and explore the general outcomes of full FHH evaluations within an expanded carrier screening (ECS) population. A retrospective chart review was conducted for 500 consults, which included 3-generation pedigrees, using data …

Quality Of Life And Psychosocial Impacts Of Persons With A Genetic Predisposition To Thoracic Aortic Dissections Or Aortic Aneurysms, Megan Soucy, Amelia Tahmassi, Nathan Hassel

Human Genetics Theses

BACKGROUND: Thoracic aortic dissections (TAD) and thoracic aortic aneurysms (TAA) can cause significant disabilities and premature sudden deaths. Modern advances in medicine and technology have increased the life expectancy for survivors of TAD or TAA; however, limited studies have measured the quality of life of affected individuals, especially those with genetically triggered aortic diseases. The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) measured the Health Related Quality of Life (HRQoL) in survivors of a TAD or TAA. Another area of impact on quality of life includes depression. One accurate measurement for depression is the 16-item …

Genetic Counselor Drift: Exploring Contributors To The Recent Growth Of Non-Clinical Genetic Counseling Positions And The Resulting Impact On The Profession., Maki Kaneko, Robert Rigobello

Human Genetics Theses

No abstract provided.

Characterization Of Myod And Myf5 Double-Knockout Muscle Stem Cells During Muscle Development, Andreea Dinicu

University Scholar Projects

MyoD and Myf5 are transcription factors that regulate myogenesis by promoting satellite cell transcription. The two genes are known to display functional redundancy. Both genes are considered myogenic determination genes and are expressed in satellite cells. The fate of myogenic precursors in the absence of both MyoD and Myf5 remains largely unknown. We aimed to begin attaining this knowledge as part of this project. We utilized a CreLoxP system to control the expression of MyoD in mice lacking Myf5. MyoD was knocked out at embryonic day (E) 11.5 during myogenesis. Limbs were collected from experimental mice following tamoxifen injection. …

Role Of Ime4 And Pho92 Proteins In Pho5 Regulation, Krishna Shah

Senior Honors Theses

In the yeast Saccharomyces cerevisiae, m6A methylation regulates the stability and translation of mRNA. Ime4, which is highly active in meiotic cells, recognizes consensus methyl sites in pre-mRNA and adds methyl groups to a small fraction of adenosine residues, whereas Pho92 binds to such methylated sites and promotes subsequent degradation. PHO5 transcripts expression is upregulated when IME4 and PHO92 are deleted. In the PHO5 transcript, near the stop codon of the open reading frame (ORF), there is a potential consensus methyl site that is predicted to be methylated, based on its location and excellent match to the consensus methylation sequence …

Transcriptomic Effects Of Dispersed Oil In A Non-Model Decapod Crustacean, Hernan Vazquez-Miranda, Brent Thoma, Juliet Wong, Darryl Felder, Keith A. Crandall, Heather Bracken-Grissom

Computational Biology Institute

Background. Oil spills are major environmental disasters. Dispersants help control spills, as they emulsify oil into droplets to speed bioremediation. Although dispersant toxicity is controversial, the genetic consequences and damages of dispersed oil exposure are poorly understood. We used RNA-seq to measure gene expression of flatback mudcrabs (Eurypanopeus depressus, Decapoda, Brachyura, Panopeidae) exposed to dispersed oil.

Methods. Our experimental design included two control types, oil-only, and oil-dispersant treatments with three replicates each. We prepared 100 base pair-ended libraries from total RNA and sequenced them in one Illumina HiSeq2000 lane. We assembled a reference transcriptome with all replicates per treatment, …