Genetics and Genomics Commons^™

Redefining Genomic Privacy: Trust And Empowerment, Yaniv Erlich, James B. Williams, David Glazer, Kenneth Yocum, Nita A. Farahany, Maynard Olson, Arvind Narayanan, Lincoln D. Stein, Jan A. Witkowski, Robert C. Kain

Faculty Scholarship

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution …

The Distribution Of Fitness Effects Of Spontaneous Mutations In Vibrio Fischeri, Chelsea K. Jones

Honors Theses and Capstones

Mutations are the ultimate source of the biological diversity on which natural selection acts, but the vast majority of these mutations are harmful. As such, mutations lead to disease states like cancer, extinction of small populations, and can drive pathogen evolution. Unfortunately, because mutations are rare and past studies have been subject to detection biases, very little is known about the distribution of fitness effects from naturally occurring mutations. In this study, we used mutation accumulation and full genome sequencing to capture naturally occurring mutations before they were exposed to the sieve of natural selection in Vibrio fischeri. We …

Investigating The Interactions Between Cyanobacteria And Vibrio Parahaemolyticus, Caroline E. Ward

Honors Theses and Capstones

One well-known pathogen that has been the topic of many recent studies is Vibrio parahaemolyticus, which causes thousands of foodborne illnesses a year, mostly from the ingestion of raw or undercooked oysters. It has been shown cyanobacteria can act as a long-term reservoir of Vibrio cholerae, another pathogenic Vibrio, by encasing the cells within mucilaginous sheaths during which Vibrios enter a viable but non-culturable state. In this study we investigated the interaction of V. parahaemolyticus with cyanobacteria to determine whether cyanobacteria aid in the longevity and survival of V. parahaemolyticus. We found that non-pathogenic V. parahaemolyticus …

The Pleiotropic Effects Of Beneficial Mutations Of Adapted Escherichia Coli Populations, Brian Scott Van Dam

Honors Theses and Capstones

Mutations that improve fitness in one environment can often be beneficial, deleterious, or neutral in alternative environments. When a single mutation effects fitness in multiple environments, it is said to be a pleiotropic, which can have important consequences for niche specialization, niche expansion, speciation, and even extinction in the face of environmental change. While previous studies have revealed that pleiotropy is nearly universal, the role of adaptive history in the spectrum of pleiotropic effects has yet to undergo detailed experimental observation. Using experimental evolution we gathered beneficial mutations in a previously adapted strain of Escherichia coli growing in the same …

The Paternal Age Effect: A Preliminary Study Of Current Challenges For Prenatal Genetics Care, Andrew Tyler Gunter

Theses and Dissertations

Advanced paternal age (APA) is related to various genetic conditions, behavioral disorders, and adverse pregnancy outcomes. Since the publication of ACMG's practice guidelines on APA in 2008, much has been learned about the causes of paternal age effect (PAE) mutations and their clinical implications. However, no guidelines exist to refer these high-risk pregnancies to prenatal genetics care, nor are effective screening techniques presently available. As such, many patients are not fully-informed about the risks to their pregnancies due to possible APA effects, and neither are are the men who have fathered these pregnancies.

Our findings support that limited APA principles …

Hidden Diversity In Sardines: Genetic And Morphological Evidence For Cryptic Species In The Goldstripe Sardinella, Sardinella Gibbosa (Bleeker, 1849), Rey C. Thomas, Demian A. Willette, Kent E. Carpenter, Mudjekeewis D. Santos

Biological Sciences Faculty Publications

Cryptic species continue to be uncovered in many fish taxa, posing challenges for fisheries conservation and management. In Sardinella gibbosa, previous investigations revealed subtle intra-species variations, resulting in numerous synonyms and a controversial taxonomy for this sardine. Here, we tested for cryptic diversity within S. gibbosa using genetic data from two mitochondrial and one nuclear gene regions of 248 individuals of S. gibbosa, collected from eight locations across the Philippine archipelago. Deep genetic divergence and subsequent clustering was consistent across both mitochondrial and nuclear markers. Clade distribution is geographically limited: Clade 1 is widely distributed in the central Philippines, while …

Basin Isolation And Oceanographic Features Influencing Lineage Divergence In The Humbug Damselfish (Dascyllus Aruanus) In The Coral Triangle, J. M. Raynal, E. D. Crandall, P. H. Barber, G. N. Mahardika, M. C. Lagman, Kent E. Carpenter

Biological Sciences Faculty Publications

The Coral Triangle is a hotspot for marine species diversity as well as for intraspecific genetic diversity. Here, we used nuclear RAG2 and mitochondrial D-Loop genes to identify deep genetic divergence among Dascyllus aruanus (Linnaeus, 1758) populations across relatively short scales within the Coral Triangle. Mitochondrial clades different by >20 mutational steps were completely isolated from one another across the distance between Java and the Lesser Sunda Islands, and also showed frequency differences in the eastern and western Philippines. Evidence for population structure in the Sulu Sea and at the Lesser Sunda Islands was also identified. Our results suggest that …

So, You Want To Use Next Generation Sequencing In Marine Systems? Insight From The Pan Pacific Advanced Studies Institute, D. A. Willette, F. W. Allendorf, P. H. Barber, D. J. Barshis, K. E. Carpenter, E. D. Crandall, W. A. Cresko, I. Fernandez-Silva, M. V. Matz, E. Meyer, M. D. Santos, L. W. Seeb, J. E. Seeb

Biological Sciences Faculty Publications

The emerging field of next-generation sequencing (NGS) is rapidly expanding capabilities for cutting edge genomic research, with applications that can help meet marine conservation challenges of food security, biodiversity loss, and climate change. Navigating the use of these tools, however, is complex at best. Furthermore, applications of marine genomic questions are limited in developing nations where both marine biodiversity and threats to marine biodiversity are most concentrated. This is particularly true in Southeast Asia. The first Pan-Pacific Advanced Studies Institute (PacASI) entitled "Genomic Applications to Marine Science and Resource Management in Southeast Asia" was held in July 2012 in Dumaguete, …

Multiplexing With Three-Primer Pcr For Rapid And Economical Microsatellite Validation, Salla Vartia, Patrick C. Collins, Thomas F. Cross, Richard D. Fitzgerald, David T. Gauthier, Philip Mcginnity, Luca Mirimin, Jens Carlsson

Biological Sciences Faculty Publications

The next generation sequencing revolution has enabled rapid discovery of genetic markers, however, development of fully functioning new markers still requires a long and costly process of marker validation. This study reports a rapid and economical approach for the validation and deployment of polymorphic microsatellite markers obtained from a 454 pyrosequencing library of Atlantic cod, Gadus morhua, Linnaeus 1758. Primers were designed from raw reads to amplify specific amplicon size ranges, allowing effective PCR multiplexing. Multiplexing was combined with a three-primer PCR approach using four universal tails to label amplicons with separate fluorochromes. A total of 192 primer pairs …

Exploration Of The Genetic Epidemiology Of Asthma: A Review, With A Focus On Prevalence In Children And Adolescents In The Caribbean, A. Mohan, A. J. Roberto, B. C. Whitehill, A. Mohan, A. Kumar

Biological Sciences Faculty Publications

Asthma is a chronic disease caused by the inflammation of the main air passages of the lungs. This paper outlines a review of the published literature on asthma. While a few studies show a trend of rising asthma cases in the Caribbean region, even fewer have explored the genetic epidemiological factors of asthma. This is a literature review that seeks to sum the body of knowledge on the epidemiology of asthma. Specifically, the major objective of the literature review is to provide a unified information base on the current state of factors involved in the genetic epidemiology of asthma. The …

Endogenous Ros Levels In C. Elegans Under Exogenous Stress Support Revision Of Oxidative Stress Theory Of Life-History Tradeoffs, Samson W. Smith, Leigh C. Latta Iv, Dee R. Denver, Suzanne Estes

Biology Faculty Publications and Presentations

Background: The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals.

Results: Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with …

The Evolutionary Dynamics Of Transcription Factors, Operators, And Their Target Genes Across Prokaryotes, Marc Del Grande

Theses and Dissertations (Comprehensive)

In prokaryotes, transcriptional regulation commonly involves a transcription factor (TF) binding to a particular conserved sequence of nucleotides (operator). Binding elicits a transcriptional response, either activation or repression. The evolution of gene regulation has been identified as a primary driver of species diversity, making it an important area of research. This work examined the dynamics of the interactions between TFs and operators, and TFs and their primary target genes in attempt to assess the rapid evolution of transcriptional regulatory networks (TRNs) across a diverse set of prokaryotes. Using software packages, operator sequences from Escherichia coli K12 were compared to every …

The Role Of Body Size On The Outcome Of Mating Interactions In Drosophila Melanogaster, Adam C. Lounsbury

Theses and Dissertations (Comprehensive)

Sexual selection is the process by which some individuals produce more and/or better quality offspring than others because they are better at securing mates. While this may be accomplished by defeating same-sex rivals (intrasexual selection), individuals of one sex (typically females) may also “decide” on the suitability of individuals of the opposite sex (typically males), resulting in intersexual selection on attractive traits. While a great deal of scrutiny has focused on how sexual selection influences male display traits, much less scrutiny has been directed toward the factors underlying female preference, including genetic variation, as well as the extent to which …

Causes And Consequences Of Female Mate Choice In Drosophila Melanogaster: A Hemiclonal Analysis, Hannah Me Tennant

Theses and Dissertations (Comprehensive)

One of Darwin’s greatest questions, the reason why females prefer elaborate sexually selected male traits and displays, was elucidated by the Fisherian coevolution of male traits and female preferences. While variation in male attractiveness and ornamentation has received much attention, there has been little attempt to evaluate the causes and consequences of intraspecific variation in components of female preference. Furthermore, demonstrating a genetic basis to female preference does not answer the question of how within-population genetic variation is maintained.

Understanding the sources of variation in potential mating interactions between males and females is important because this variation determines the strength …

Data From: Further Examination Of The Geographic Range Of Eriogonum Corymbosum Var. Nilesii (Polygonaceae), Mark W. Ellis, Paul G. Wolf, Shannon Bardot, James A. Walton, Carol A. Rowe, Sarah Kulpa, Karen E. Mock

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The buckwheat Eriogonum corymbosum is widely distributed throughout the southwestern United States, forming a complex of eight varieties. Eriogonum corymbosum var. nilesii is a primarily yellow-flowered taxon reported only from Clark County, Nevada. A previous genetic study by our research group found that variety nilesii is genetically distinct from other E. corymbosum varieties, based on a limited number of populations. Here, we assess genetic variation in 14 newly sampled yellow-flowered populations from southern Nevada, southern Utah, and northern Arizona, and compare them to genetic variation in six populations of previously determined E. corymbosum varieties. Of the new populations, we identified …

Did Androgen-Binding Protein Paralogs Undergo Neo- And/Or Subfunctionalization As The Abp Gene Region Expanded In The Mouse Genome?, Robert C. Karn, Amanda G. Chung, Christina M. Laukaitis

Scholarship and Professional Work - LAS

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the …

Understanding Crx-Associated Retinopathies Using Animal Models, Nicholas Minh Abell Tran

All Theses and Dissertations (ETDs)

Cone-rod homeobox: CRX) protein is a "paired-like" homeodomain transcription factor that is essential for regulating rod and cone photoreceptor transcription. Mutations in human CRX are associated with the dominant retinopathies Retinitis Pigmentosa: RP), Cone-Rod Dystrophy: CoRD) and Leber Congenital Amaurosis: LCA), with variable severity. The goal of my dissertation project was to develop and characterize animal models to understand genetic mechanisms of phenotypic diversity in CRX-associated disease. Heterozygous Crx Knock-Out: KO) mice: "+/-") have normal vision as adults and fail to model the dominant human disease.

We generated two Crx Knock-IN: K-IN) mouse models: CrxE168d2: "E168d2") and CrxR90W: "R90W"), which …

Beef Cattle Body Temperature During Climatic Stress: A Genome-Wide Association Study, Jeremy T. Howard, Stephen D. Kachman, Warren M. Snelling, E. John Pollak, Daniel C. Ciobanu, Larry A. Kuehn, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Cattle are reared in diverse environments and collecting phenotypic body temperature (BT) measurements to characterize BT variation across diverse environments is difficult and expensive. To better understand the genetic basis of BT regulation, a genome-wide association study was conducted utilizing crossbred steers and heifers totaling 239 animals of unknown pedigree and breed fraction. During predicted extreme heat and cold stress events, hourly tympanic and vaginal BT devices were placed in steers and heifers, respect i v e l y. I n d i v i dua l s we r e genotyped with t h e BovineSNP50K_v2 assay and data …

Interaction-Based Discovery Of Functionally Important Genes In Cancers, Dario Ghersi, Mona Singh

Interdisciplinary Informatics Faculty Publications

A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline (http://canbind.princeton.edu) for mapping large-scale cancer exome data …

The Diversity Of Quantitative Trait Loci In Yeast Sporulation Efficiency, Kimberly Lorenz

All Theses and Dissertations (ETDs)

A complex trait is one that exhibits continuous phenotypic variation due to genetic variation in many quantitative trait genes: QTGs). The ultimate goal of genetics is to relate genotype to phenotype; in the case of complex traits this requires a better understanding of what types of genes harbor causal natural variation, and what form the variation takes. Here I describe two experiments using the model complex trait of sporulation efficiency in the yeast Saccharomyces cerevisiae, one to specifically investigate how small effects contribute to a quantitative trait and the other to determine whether certain types of genes are more likely …