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- All Subjects: Genetics
Description
ABSTRACT Whole genome sequencing (WGS) and whole exome sequencing (WES) are two comprehensive genomic tests which use next-generation sequencing technology to sequence most of the 3.2 billion base pairs in a human genome (WGS) or many of the estimated 22,000 protein-coding genes in the genome (WES). The promises offered from WGS/WES are: to identify suspected yet unidentified genetic diseases, to characterize the genomic mutations in a tumor to identify targeted therapeutic agents and, to predict future diseases with the hope of promoting disease prevention strategies and/or offering early treatment. Promises notwithstanding, sequencing a human genome presents several interrelated challenges: how to adequately analyze, interpret, store, reanalyze and apply an unprecedented amount of genomic data (with uncertain clinical utility) to patient care? In addition, genomic data has the potential to become integral for improving the medical care of an individual and their family, years after a genome is sequenced. Current informed consent protocols do not adequately address the unique challenges and complexities inherent to the process of WGS/WES. This dissertation constructs a novel informed consent process for individuals considering WGS/WES, capable of fulfilling both legal and ethical requirements of medical consent while addressing the intricacies of WGS/WES, ultimately resulting in a more effective consenting experience. To better understand components of an effective consenting experience, the first part of this dissertation traces the historical origin of the informed consent process to identify the motivations, rationales and institutional commitments that sustain our current consenting protocols for genetic testing. After understanding the underlying commitments that shape our current informed consent protocols, I discuss the effectiveness of the informed consent process from an ethical and legal standpoint. I illustrate how WGS/WES introduces new complexities to the informed consent process and assess whether informed consent protocols proposed for WGS/WES address these complexities. The last section of this dissertation describes a novel informed consent process for WGS/WES, constructed from the original ethical intent of informed consent, analysis of existing informed consent protocols, and my own observations as a genetic counselor for what constitutes an effective consenting experience.
ContributorsHunt, Katherine (Author) / Hurlbut, J. Benjamin (Thesis advisor) / Robert, Jason S. (Thesis advisor) / Maienschein, Jane (Committee member) / Northfelt, Donald W. (Committee member) / Marchant, Gary (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2013
Description
Gene-centric theories of evolution by natural selection have been popularized and remain generally accepted in both scientific and public paradigms. While gene-centrism is certainly parsimonious, its explanations fall short of describing two patterns of evolutionary and social phenomena: the evolution of sex and the evolution of social altruism. I review and analyze current theories on the evolution of sex. I then introduce the conflict presented to gene-centric evolution by social phenomena such as altruism and caste sterility in eusocial insects. I review gene-centric models of inclusive fitness and kin selection proposed by Hamilton and Maynard Smith. Based their assumptions, that relatedness should be equal between sterile workers and reproductives, I present several empirical examples that conflict with their models. Following that, I introduce a unique system of genetic caste determination (GCD) observed in hybrid populations of two sister-species of seed harvester ants, Pogonomyrmex rugosus and Pogonomyrmex barbatus. I review the evidence for GCD in those species, followed by a critique of the current gene-centric models used to explain it. In chapter two I present my own theoretical model that is both simple and extricable in nature to explain the origin, evolution, and maintenance of GCD in Pogonomyrmex. Furthermore, I use that model to fill in the gaps left behind by the contributing authors of the other GCD models. As both populations in my study system formed from inter-specific hybridization, I review modern discussions of heterosis (also called hybrid vigor) and use those to help explain the ecological competitiveness of GCD. I empirically address the inbreeding depression the lineages of GCD must overcome in order to remain ecologically stable, demonstrating that as a result of their unique system of caste determination, GCD lineages have elevated recombination frequencies. I summarize and conclude with an argument for why GCD evolved under selective mechanisms which cannot be considered gene-centric, providing evidence that natural selection can effectively operate on non-heritable genotypes appearing in groups and other social contexts.
ContributorsJacobson, Neal (Author) / Gadau, Juergen (Thesis advisor) / Laubichler, Manfred (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2012
Description
The knowledge of medical genetics is currently used with prenatal testing, and the advancements in the field of behavioral genetics may someday allow for its use with prenatal testing as well. The use of prenatal procedures for medical phenotypes has its own implications and should these techniques be used for behavioral phenotypes, such implications can also apply. The complexity of behavior in terms of the factors that may affect it, along with the way it is conceptualized and perceived, adds further implications for prenatal testing of it. In this thesis, I discuss the qualitative, quantitative, and historical facets of prenatal testing for medical and behavioral phenotypes and the undercurrent of eugenics. I do so by presenting an example of the medical phenotype (cystic fibrosis) as a case for envisioning the implications of medical phenotypes before delving into examples of behavioral phenotypes (aggression, impulsivity, extraversion, and neuroticism) in order to explore the implications shared with those for medical phenotypes as well as those unique to it. These implications then set the foundation for a discussion of eugenics, and the considerations for how behavioral genetics with prenatal testing may give way to a modern form of it.
ContributorsMinai, Mandana (Author) / Maienschein, Jane (Thesis director) / Robert, Jason (Committee member) / Magnus, David (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2014-05
Description
In vitro gametogenesis (IVG) research has been growing in countries like Japan, US, and China after the development of stem cell research and other scientific advancements as well as because of the perception of infertility as a domestic and international problem. IVG research’s progress has been deliberated internationally, with discussion of questions, challenges, and possibilities that have arisen and may arise in the future as the technology is adopted by different countries. The first section introduces the meaning of IVG, explains the importance of review by scientists and citizens for IVG, and describes a rise in infertility reported in multiple developed countries that could be addressed by IVG. The second section discusses IVG’s applications and implications using 5 ethical categories articulated by Obama’s Presidential Commission for the Study of Bioethical Issues: Public Beneficence, Responsible Stewardship, Intellectual Freedom and Responsibility, Democratic Deliberation, and Justice and Fairness. These five ethical principles were intended for analysis of emerging technologies, and IVG is an emerging technology with possible integration into clinical settings. Among the principles, it seemed that a major weak point of inquiry concerns LGBT+ and disability inclusion, especially of gender dysphoric and transgender people who may experience higher rates of infertility and have a harder time conceiving due to a mix of discrimination, gender dysphoria, and infertility due to hormone replacement therapy (HRT) treatment or gender/sex reassignment surgeries (GRSs/SRSs) that may impair or remove reproductive body parts. A number of other ethical considerations arise about this technology.
ContributorsVillarreal, Lance Edward (Author) / Maienschein, Jane (Thesis director) / Ellison, Karin (Committee member) / Wilson-Rawls, Jeanne (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
How is knowledge created at the intersections between basic science, biotechnology, and industry? Gene drives are an interesting example, as they combine a long-standing interest with a recent technological breakthrough and a new set of commercial applications. Gene drives are genes engineered such that they are preferentially inherited at a frequency greater than the typical Mendelian fifty percent ratio. During the historical and conceptual evolution of gene drives beginning in the 1960s, there have been many innovations and publications. Along with that, gene drive science developed considerable public attention, explosion of new scientists, and variation in the way the topic is discussed. It is now time to look at this new organization of science using a systematic approach to characterize the system that has enabled knowledge to grow in this scientific field. This project breaks new ground in how knowledge advances in genetic engineering science, and how scientists understand what a “gene drive” is through analysis of language, communities, and other social factors. In effect, this research will advance multiple fields and enable a deeper understanding of knowledge and complexity. This project documents patterns of publication, collaborative relationships, linguistic variation, innovation, and knowledge expansion. The results of computational analysis provide an in-depth and complete characterization of the structure, dynamics, and evolution of scientific knowledge found in the gene drive technology. Further, time series analysis of the multiple layers of discourse enabled a diachronic connective mapping of collaborative relationships and tracked linguistic variation and change, highlighting where ambiguous language may appear, improving and creating more cohesive scientific language.
Overall, depicting the structure, dynamics, and evolution of scientific knowledge during a novel eruption of scientific complexity can shed light on the factors that can lead to: (1) improved scientific communication, (2) reduction of scientific progress, (3) new knowledge, and (4) novel collaborative relationships. Therefore, characterizing the current technological, methodological, and social contexts that can influence scientific knowledge.
ContributorsOToole, Cody Lane (Author) / Laubichler, Manfred (Thesis advisor) / Collins, James P (Committee member) / Simeone, Michael (Committee member) / Evans, James (Committee member) / Arizona State University (Publisher)
Created2021
Description
This dissertation investigates the convergence of the nation-state, biomedicine and (bio)capital around the construction of sickle cell disease as a subaltern disorder in the caste-based society of India. It inquires how sickle cell disease that developed evolutionarily due to environmental factors—and that is also globally racialized as a “Black disease”—has come to be associated with subaltern communities, particularly the indigenous, traditionally non-Hindu Adivasi communities of India. Such a subaltern association characterizes Adivasi biologies as inherently genetically “risky” thereby providing a biopolitical mandate to the Hindu-majoritarian Indian State to carry out biomedical interventions through promissory biocapital in the name of democratic inclusion. I center on the illness narratives of subaltern sickle cell sufferers to highlight how the caste-ization of sickle cell bodies in biomedical and policy discourses, and the attendant biocapital prospecting of subaltern biologies, are nonetheless challenged by communities through their lived experiences. Viewing this association from the Adivasi standpoint—marked by continuous dispossession and displacement—illuminates not only the biopolitical governance of subaltern reproduction by the Indian State. A primary objective of my dissertation project is also to use precarity as an epistemic site for interrogating the scopes and limits of a novel biopower formed by the nexus between the State, national biomedicine and transnational biocapital. This dissertation is therefore an attempt at unearthing the subjugated knowledges of Adivasi communities regarding alternative modes of existing in the world that continuously resist the assimilatory power of race, caste and capital. In ethnographically centering narratives of suffering among doubly (socially/economically) marginalized communities, the project illuminates the contradictions between public health measures that emphasize on sickle cell management through biomedical technologies of reproductive screening and the material conditions of sickle cell sufferers struggling to access basic medical care. This dissertation therefore juxtaposes policy interventions against community articulations of reproductive freedom that posits community health work as the fulcrum for developing reproductively just ecologies. At the same time, in utilizing multi-modal and multi-sited ethnographic methods, the project also contributes towards developing decolonial and digital ethnographic methods that are attentive to the aggravated precarity of marginalized communities in a pandemic prone world.
ContributorsDas, Sanghamitra (Author) / Smith, Lindsay A. (Thesis advisor) / Quan, H.L.T. (Committee member) / Maienschein, Jane (Committee member) / Prasad, Indulata (Committee member) / Robert, Jason (Committee member) / Arizona State University (Publisher)
Created2023
Description
Transgenic experiments in Drosophila have proven to be a useful tool aiding in the
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
ContributorsStinchfield, Michael J (Author) / Newfeld, Stuart J (Thesis advisor) / Capco, David (Committee member) / Laubichler, Manfred (Committee member) / Arizona State University (Publisher)
Created2019