Master of Science, The Ohio State University, 2022, Genetic Counseling

Although many clinical genetic testing laboratories collect race, ethnicity, and ancestry (REA) information, there are documented issues inherent to the process. Obtaining a better understanding of clinical genetic testing laboratory practices surrounding REA data provides an opportunity to better understand how they contribute to and mitigate social inequities in genetic medicine. To investigate current REA data practices, this study aimed to characterize clinical genetic testing laboratory REA data collection, use, and storage practices as reported by laboratory employees. Participants (n=57) completed a survey addressing current collection, use, and storage practices, as well as opinions regarding REA data. Most laboratories reportedly collect (95%, n=41), use (82%, n=33), and store (71%, n=34) REA data. REA data collection and use varies in relation to test type, clinical specialty, admixed ancestry, and collection source. All (100%, 10/10) employees who perform variant interpretation (VI) report inclusion of population-based criteria in their VI protocol, but only half use REA data in VI very frequently (50%, 4/8), while half use it very infrequently (50%, 4/8). Participants had a greater endorsing than refuting opinion about the need for improved REA data practices (67%, 24/36) and transparency (38%, 13/34). Nearly half of participants reported REA data practices contribute to systemic racism (41%, 13/42) and healthcare inequities (47%, 14/30). Most participants reported it is the responsibility of laboratories to assess their REA data practices (70%, 21/30) and expressed at least some willingness to contribute to developing REA data practice guidelines (45%, 13/29). Quantifiably characterizing laboratory practices via employee reports builds opportunities for research further identifying factors exacerbating and mitigating any contributions REA data practices make to systemic issues, and may aid in the development of REA data practice guidelines.

Committee: Laiken Peterson (Advisor); Jordan Brown (Committee Member); Matthew Avenarius Dr. (Committee Member) Subjects: Biology; Biomedical Research; Demographics; Genetics; Health; Health Care; Health Care Management; Health Sciences; Medical Ethics; Medicine; Molecular Biology

Master of Arts (MA), Bowling Green State University, 2021, American Culture Studies

The marketing of DNA ancestry tests plays a major role in circulating ideas about how the public should interpret DNA test results, the way DNA connects us to people around the world, and the connections between race, ethnicity, nationality, genetics, and ancestry. This thesis contributes to the literature on DNA ancestry testing marketing by examining themes not thoroughly explored in previous studies: ancestry travel and DNA tests as anti-racist tools. Through a textual analysis of Ancestry, 23andMe, and MyHeritage DNA television advertisements, I analyze how these advertisements represent travel based on one's DNA ancestry test, how populations and regions around the world are represented, how race, ethnicity, and nationality are discussed, and how the root causes of racism are defined. My analysis is informed by critiques of DNA tests made by scholars in ethnic studies, biology, anthropology, and science and technology studies who argue that by taking it as a given that race and ethnicity have meaning at a genetic level, genetic scientists participate in the geneticization of race. I argue that these advertisements represent ancestry travel as journeys of self-discovery where the traveler connects with others through consumption practices. The populations the traveler visits are represented without specificity and are shown in positions of service to the traveler. By promoting the idea that DNA tests are objective arbiters of belonging, these advertisements redefine race, ethnicity, and nationality as labels that describe one's genetic ancestry and remove the agency from communities to decide who is and is not a member of their community. These advertisements promote the idea that there is a genetic component to race and ethnicity and suggest that contemporary inequalities along racial and ethnic lines are a product of innate genetic difference as opposed to historical and political processes. Thus, these ads circulate ideas that echo early 20th century (open full item for complete abstract)

Committee: Susana Peña Ph.D (Advisor); Michaela Walsh Ph.D (Committee Member); Vibha Bhalla Ph.D (Committee Member) Subjects: American Studies; Ethnic Studies; Mass Media

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

This dissertation focuses on advancing machine learning applications in genomic sequencing, emphasizing the need for model transparency and reproducibility. We introduce two innovative methods to enhance genomics-guided precision medicine: inferring genetic ancestry using genome sequence data and identifying variants in tumor-only RNA sequencing. Knowledge of a patient's genetic ancestry can inform clinical decisions, from genetic testing and health screenings to medication dosages. Our first method, SNVstory, predicts genetic ancestry from single nucleotide variants with high accuracy across 36 populations. We employ a novel approach to simulate individual samples from aggregated allele frequencies of known populations, thus increasing the number and diversity of training variants. Additionally, detailed feature importance analyses provide insights into the genomic features most influential in ancestry prediction, enhancing its clinical utility. Transitioning to variant calling in RNA sequencing data, we explore its potential to enhance our understanding of pediatric cancer biology. Our second method, VarRNA, processes tumor-only RNA sequencing data to call variants and accurately classify them as germline, somatic, or artifacts. Applying VarRNA to pediatric cancer samples revealed crucial insights into allele-specific expression patterns in key cancer-driving genes. VarRNA represents a groundbreaking approach that integrates expression data with variant identification, opening new avenues for cancer biology research and clinical care. These transparent and reproducible methods significantly broaden the utility and impact of genomics-guided precision medicine, promising substantial advancements in the field.

Committee: Elaine Mardis (Advisor); Peter White (Advisor); Jeffrey Parvin (Committee Member); Rachid Drissi (Committee Member) Subjects: Bioinformatics; Biomedical Research

Master of Arts, The Ohio State University, 2023, Sociology

Given that Latinxs are the largest ethnoracial minority group in the United States, their political attitudes, behaviors, and policy preferences are important to understand due to their potential ability to (re)shape inequality in United States. Scholars have developed different theoretical explanations to describe variation in Latinx attitudes and preferences for immigration and immigration policy, yet less is known about ancestral sub-group variation. In this paper, I consider Latinx political thought and how ancestral sub-group variation may be related to one's understandings of, and experiences with, immigration and borders. Using data from the 2006 Latino National Survey, I perform a series of logistic regression models to examine whether ancestral sub-group membership, self-reported skin tone, and sociodemographic and political orientation variables shape undocumented immigration public policy preferences among the Latinx population. I highlight three important findings. First, Latinxs preferences related to undocumented immigration policies vary dramatically by ancestral sub-group membership. Second, self-reported skin tone does not appear to be a significant predictor of policy preference in this sample, nor does it account for the substantial differences by ancestral subgroup. Lastly, sociodemographic and political orientation measures are important pathways through which ancestral sub-groups are related to policy preferences, e.g. through generation, education and income. The results of this paper reveal the critical need for demographic analyses to disrupt hegemonic, monolithic assumptions of Latinidad.

Committee: Reanne Frank (Advisor); Vincent Roscigno (Committee Member); Townsand Price-Spratlen (Advisor) Subjects: Sociology

Master of Science, The Ohio State University, 2022, Genetic Counseling

Background: Race, ethnicity, and ancestry (REA) are distinct terms that are often used interchangeably to refer to ascribed social identities. Within the medical setting, REA is commonly collected as demographic information with race and ethnicity being frequently used as surrogates for ancestral background. Currently, patient- or provider-reported REA is being used in biomedical and healthcare research instead of genetic ancestry, which is scientifically interpreted. The utilization of patient- or provider-reported REA in the clinical interpretation of potentially disease-associated variants may result in inaccurate risk assessment. Genetic counselors (GCs) often collect patient-reported REA as part of the pedigree construction process. Methods for obtaining patient-reported REA are currently not well characterized. This study aims to do the following: determine the proportion of genetic counselors who currently collect patient-reported REA during routine genetic counseling encounters, characterize how genetic counselors ask their patients about REA, and describe the characteristics of genetic counselors that do collect REA information as well as those that do not. An additional exploratory aim of investigating whether or not genetic counselors can determine race, ethnicity, and ancestry emerged during survey construction. Methods: 239 board-certified genetic counselors were recruited by electronic means to complete a 20-question online survey assessing GCs' perception of race, ethnicity, and ancestry, the current practices of GCs, and the demographics of GCs. Data regarding GCs' REA perception, current practices, and demographics were analyzed using descriptive statistics and chi-squared tests. Statistical analysis was not significant. Results: More participants ask patients for ancestry data (93%) in comparison to ethnicity (65%) or race data (40%). 75% of participants collect REA data from patients directly. Phrases and/or terms associated with “ethnicity”, “cou (open full item for complete abstract)

Committee: Jordan Brown (Advisor); Leigha Senter-Jamieson (Committee Member); Damara Hamlin (Committee Member); Vivian Pan (Committee Member); Barbara Harrison (Committee Member) Subjects: Genetics; Health Care; Health Sciences

Ph.D., Antioch University, 2022, Leadership and Change

Reframing Leadership Narratives Through the African American Lens explores the context-rich experiences of Black Museum executives to challenge dominant cultural perspectives of what constitutes a leader. Using critical narrative discourse analysis, this research foregrounds under-told narratives and reveals the leadership practices used to proliferate Black Museums to contrast the lack of racially diverse perspectives in the pedagogy of leadership studies. This was accomplished by investigating the origin stories of African American executives using organizational leadership and social movement theories as analytical lenses for making sense of leaders' tactics and strategies. Commentary from Black Museum leaders were interspersed with sentiments of “Sankofa” which signify the importance of preserving the wisdom of the past in an effort to empower current and future generations. This study contributes to closing the gap between race and leadership through a multidimensional lens, while amplifying lesser-known histories, increasing unexplored narrative exemplars, and providing greater empirical evidence from the point of view of African American leaders. This dissertation is available in open access at AURA (https://aura.antioch.edu) and OhioLINK ETD Center (https://etd.ohiolink.edu).

Committee: Donna Ladkin Ph.D. (Committee Chair); Lemuel Watson Ph.D. (Committee Member); Damion L. Thomas Ph.D. (Committee Member) Subjects: African American Studies; African Americans; American History; Arts Management; Black History; Black Studies; History; Museum Studies; Museums; Organization Theory; Organizational Behavior

Master of Science, University of Toledo, 2017, Biology (Cell-Molecular Biology)

Several companies over the past decade have started to offer ancestry analysis, the most notable company being 23andMe. For a relatively low price, 23andMe will sequence select variants in a person's genome to determine where their ancestors came from. Since 23andMe is a private company, the exact techniques and algorithms it uses to determine ancestry are proprietary. Many customers have wondered about the accuracy of these results, often citing their own genealogical research of recent ancestors. To bridge the gap between 23andMe and the public, we sought to provide a tool that could assess the ancestry results of 23andMe. Using publicly available 23andMe genotype files, we constructed a program pipeline that takes these files and compares them against genomes from the 1000 Genomes Project. We constructed haplotypes from the 23andMe file by converting 50 adjacent SNPs (single nucleotide polymorphisms) into haplotypes and comparing them against the haplotypes of 2504 individuals in the Phase 3 data from the 1000 Genome Project. To smooth the data, we bundled together six of our haplotype segments to form an “IBD segment” (Identity-by-descent segment) and used a point scoring system to calculate the highest matching population. Our pipeline determined ancestry results for 57 individuals with similar results to 23andMe. Fifty of our subjects showed European ancestry, while the other seven subjects showed ancestry from East Asia, Africa, America, and South Asia. Of our 5 geographic categories (South Asia, Africa, America, Europe, East Asia), 98% of our subjects showed ancestral representation from 4 of the 5 categories. In addition to ancestry, we also investigated IBD sharing across populations, particularly IBD segments in the Human Leukocyte Antigen (HLA) region on chromosome 6. We hope this tool will help 23andMe customers and those of similar genotyping companies understand the methods used to determine ancestry and verify their results.

Committee: Alexei Fedorov (Committee Chair); Robert Blumenthal (Committee Member); Sadik Khuder (Committee Member) Subjects: Bioinformatics

Doctor of Philosophy, Case Western Reserve University, 2017, Epidemiology and Biostatistics

There has been increasing interest in studying the ancestral spectrum in admixed individuals, such as African Americans and Latino Americans. Investigating the different ancestral proportions across an individual's genome, i.e. the local ancestries, is important in genetic studies. Many methods have been developed to infer the local ancestries in admixed individuals from their genotype data. A few of them have attempted to extend their methodologies to small nuclear families, but none can be applied to large pedigrees. We developed a method named FamANC that is able to improve the accuracy of local ancestry inference in large pedigrees by: 1) using existing software to infer local ancestries for all individuals in a family, assuming they are unrelated, 2) improving inference accuracy by correcting the inference errors. From our simulations, FamANC reduced the local ancestry estimation errors by over 20%. The second part of this dissertation is on searching for the epistasis of fitness evidence using local ancestries. The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years. However, existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting non-independence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two-locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints. In this study, we theoretically demonstrate that fitness epistasis can create correlation of local ancestry between unlinked loci that can be examined. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes (open full item for complete abstract)

Committee: Xiaofeng Zhu (Committee Chair); Robert Elston (Committee Member); Nathan Morris (Committee Member); Xiang Zhang (Committee Member) Subjects: African Americans; Bioinformatics; Biostatistics; Epidemiology; Genetics; Statistics

MFA, Kent State University, 2014, College of the Arts / School of Art

I aim to tell a story about generational connection between the women in my family expressed through digitally printed textiles and figural forms. In looking back on my own heritage, material objects in many cases have been all that are left to tell the story of the past. I research these objects that reflect myself, both grandmothers, mother and soon to be daughter. The objects include letters, handmade garments, jewelry, printed documents and domestic articles. Using this imagery I digitally developed textile patterns telling a story for each woman. The work consists of five textile sculptures and ten hanging textile panels metaphorically representing the five women. Hung together their presence creates an identity that embodies each woman individually as well as the family as a whole. This installation of visual narrative serves as an example of how we can use technology to create a fusion of past and present in order to preserve our memories and kinship.

Committee: Janice Lessman-Moss (Advisor); Noel Palomo-Lovinski (Committee Member); Kathleen Browne (Committee Member) Subjects: Fine Arts; Textile Research

Doctor of Musical Arts, The Ohio State University, 2003, Music

For decades, American flutists have sought to identify specific traits that define their playing as a whole. While the “French School” has been characterized by a preoccupation with tone, a standard repertoire, and set of teaching materials written by Paris Conservatoire professors, no such definition can yet be set forth for the “American School.” This document provides a clear starting point for research into the what, where, why, and how of the “American Flute School” by first identifying who is associated with that school. By tracing the lineage of transverse flute playing from teacher to student through the past 300 years, we may identify orchestral flutist, soloist, and teacher, Georges Barrere, as a primary influence upon American flute playing. Barrere and his students – and his students' students – have taught approximately 91% of all living flutists in the United States today. Of that vast number, approximately 87% can trace their heritage (through one or more of their teachers) to Barrere student William Kincaid, renowned flutist of the Philadelphia Orchestra and pedagogue at the Curtis Institute of Music. It is important to note that most modern musicians study with more than one teacher over the course of their career (usually between three and eight). By looking at the data from different perspectives, we can see a second important tradition of flute playing descend from Georges Laurent, principal flutist of the Boston Symphony Orchestra and instructor at the New England Conservatory of Music, including approximately 59% of American flutists. A third tradition of flute playing in America (including roughly 55% of American flutists) descends from French flutist and pedagogue, Marcel Moyse, who taught summer classes in Vermont for several decades after a lengthy career in Paris. Each of these influential pedagogues graduated from the Paris Conservatoire, having studied with the distinguished master, Paul Taffanel. A lengthy appendix of biographical in (open full item for complete abstract)

Committee: Katherine Jones (Advisor); Lois Rosow (Other); Christopher Weait (Other) Subjects: Music

Doctor of Philosophy, Case Western Reserve University, 2008, Epidemiology and Biostatistics

Case-control studies are susceptible to false positive findings because of population stratification either when allele frequencies differ between cases and control due to differences in ancestry distribution or when there is unrecognized stratification within cases or controls due to the presence of subgroups with different ancestries. Thus, accurate estimates of the admixture proportions at an individual level are important. Statistical methods exist to infer individual ancestry from genetic data, and to assign (probabilistically) admixed individuals jointly to two or more populations. We seek to improve the accuracy of individual ancestry estimates (IAEs) using these statistical approaches, thereby reducing the number of false-positive findings (due to ancestry) in case-control studies.We evaluate several approaches to improve the accuracy of the IAEs using the methods implemented in Structure (Pritchard, Stephens, and Donnelly 2000), and in the principal components approach (Zhang et al. 2002). First, we considered whether using prior information to preselect the prior admixture distribution parameter (α) would improve the IAEs. We show that the IAEs are insensitive to the preselected α parameter. Second, we assess the importance of including pseudo-ancestral subjects (PAs) during the inference process and conclude that including PAs does not improve the accuracy of the IAEs when moderately or highly informative markers for ancestry are used. Third, we determine the number of markers required to obtain accurate IAEs, given the absolute allele frequency difference (δ) between parental populations of the preselected SNPs, the level of divergence between the parental populations, and the genetic contribution from the parental populations to the admixed sample. We show that the number of SNPs necessary to infer accurate IAEs not only depends on the distribution of δ values, but also on the range of ancestry contribution from the population that contributes less to t (open full item for complete abstract)

Committee: Katrina Goddard PhD (Committee Chair); Ronald Blanton PhD, MD (Committee Member); Robert Elston PhD (Committee Member); Luo Yuqun PhD (Committee Member); Zhu Xiaofeng PhD (Committee Member) Subjects: Epidemiology; Genetics

Master of Science, University of Akron, 2007, Geography

This study examines contemporary and historic residential patterns of six European ethnic/ancestry groups in U.S. metropolitan areas. Specifically, Pittsburgh and Cleveland are used as case studies. The study attempts to support the hypothesis that the residential patterns exhibited by European ethnic groups are specific to the urban areas in which they reside. Analysis is conducted using four statistical measures (dissimilarity index, isolation index, delta, and Moran's i) calculated by census tract for both study areas, which consist of the two counties in which Pittsburgh and Cleveland are located – Allegheny County and Cuyahoga County, respectively. Data from 1940 and 2000 U.S. Censuses are used in the calculations, the results of which are compared among ethnic groups and between the two study areas to verify the hypothesis.

Committee: Robert Kent (Advisor) Subjects:

MS, University of Cincinnati, 2013, Medicine: Genetic Counseling

Background: Population studies from a single study site may result in unexpected substructure, especially in the United States, where admixture is common. Thus it is important to examine the population substructure of US cities to better understand potential biases for genetic studies. This study examines the continental structure and substructure of the greater Cincinnati area. Methods: Study subjects included self-reported white/Caucasian and black/African American participants in the Cincinnati Genomic Control Cohort (GCC). Principal component analyses (PCA) and Eigensoft were used to analyze the data, chromosome by chromosome, to determine if we could separate both population groups and assess the level of agreement between self-reported and genetic race. Additionally, within the self-reported white cohort, population substructure was evaluated using markers from several chromosomes at varying allele frequencies (0-5%, 6-20%, and 21% +) and three sets of ancestry informative markers (AIMs). Results: Clear continental structure was observed when comparing self-reported white and black populations. The overall rate of agreement between self-reported and genetic race was 99% (981/983). There was no substructure identified in the self-reported white population when using three different sets of AIMs however distinct clusters were present when using rare, medium, and common alleles. Moreover, different chromosomes produced different clustering patterns, when examined at the same allele frequency. Conclusions: Self-reported race is a good tool for determining continental ancestry; however self-reported race may not be sufficient when trying to achieve homogenous cases and controls. Specifically, if identified substructure differs based on the variants selected, it will be important to ensure that a robust set of variants are selected, that reflect variation across the genome, to detect potential population stratification. If variation is not accounted for, (open full item for complete abstract)

Committee: Mehdi Keddache Ph.D. (Committee Chair); Cynthia Prows (Committee Member); Lisa Martin Ph.D. (Committee Member) Subjects: Genetics