Genetics and Genomics Commons^™

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …

Deciphering The Genetic Architecture Of Key Female Floral Traits For Hybrid Wheat Seed Production, Juan David Jimenez

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Wheat (Triticum aestivum L.) is a staple cereal that provides 20% of the calories and proteins in human intake (Ray et al., 2013). Global population is projected to increase to 9.7 billion by 2050. Food production must increase by 70% to feed this future population. Wheat production is in crisis due to political and environmental challenges and is projected to decline by 0.8% in 2022 (FAO, 2022). To ensure food security yield genetic gain must increase by around 1.4% annually. Taking advantage of heterosis, hybrid wheat has the potential to boost grain yield. However, hybrid wheat seed production systems …

Retrospective Varying Coefficient Association Analysis Of Longitudinal Binary Traits, Gang Xu

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many genetic studies contain rich information on longitudinal phenotypes that require powerful analytical tools for optimal analysis. Genetic analysis of longitudinal data that incorporates temporal variation is important for understanding the genetic architecture and biological variation of complex diseases. Most of the existing methods assume that the contribution of genetic variants is constant over time and fails to capture the dynamic pattern of disease progression. However, the relative influence of genetic variants on complex traits fluctuates over time.We developed several tests to fill the gap of analyzing time-varying genetic effects in longitudinal GWAS for binary traits. First, we propose a …

Interneuronal Network Model Of Theta-Nested Fast Oscillations Predicts Differential Effects Of Heterogeneity, Gap Junctions And Short Term Depression For Hyperpolarizing Versus Shunting Inhibition, Guillem Via, Roman Baravalle, Fernando R. Fernandez, John A. White, Carmen C. Canavier

School of Medicine Faculty Publications

Theta and gamma oscillations in the hippocampus have been hypothesized to play a role in the encoding and retrieval of memories. Recently, it was shown that an intrinsic fast gamma mechanism in medial entorhinal cortex can be recruited by optogenetic stimulation at theta frequencies, which can persist with fast excitatory synaptic transmission blocked, suggesting a contribution of interneuronal network gamma (ING). We calibrated the passive and active properties of a 100-neuron model network to capture the range of passive properties and frequency/current relationships of experimentally recorded PV+ neurons in the medial entorhinal cortex (mEC). The strength and probabilities of chemical …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Landscape Genomics Of The Tussock Cottongrass (Eriophorum Vaginatum) And The Dwarf Birch (Betula Nana) In North Central Alaska, Elizabeth Stunz

Open Access Theses & Dissertations

Global climate change has resulted in geographic range shifts of flora and fauna at a global scale. Extreme environments, like the Arctic, are seeing some of the most pronounced changes. This region covers 14% of the Earthâ??s land area, and while many arctic species are widespread, understanding ecotypic variation at the genomic level will be important for elucidating how range shifts will affect ecological processes. Increase in shrub cover is a major effect of ongoing climate change in arctic tundra ecosystems. The relative increases in abundance and cover of shrub species such as birch, willow, and alder (Betula, Salix, and …

Potential Fitness Trade-Offs Of Elevated Esterase Activity Associated With Insecticide Resistance In The Mosquito Culex Quinquefasciatus, Timothy Schulte

Electronic Theses, Projects, and Dissertations

One of the current major issues in the control of vector-borne disease is resistance to insecticides. Resistance to one or more insecticides has appeared in over 580 different arthropod species. Widespread resistance has led to the field of Insecticide Resistance Management (IRM). The goal of IRM is to develop insecticide-use strategies that prevent or slow down the evolution of resistance. Computer models have shown that more effective IRM strategies rely on the assumption that resistance carries a fitness cost in the absence of insecticide use.

In the mosquito Culex quinquefasciatus resistance to certain organophosphate insecticides is caused by an increased …

The Effect Of Spirulina Platensis Algae Inclusion In Feed Of Commercial Broilers Subjected To Cyclic Heat Stress, Kirsten Shafer

Graduate Theses and Dissertations

The effect of Spirulina platensis inclusion in feed of commercial broilers was evaluated over one experiment. The study aimed to investigate the effects of Spirulina platensis freshwater algae inclusion on live performance and processing characteristics of commercial broilers subjected to daily cyclic heat stress. Day old Ross 708 male broilers were placed into 8 environmentally controlled chambers. At d 21, four chambers remained on a control diet containing no algae (CON) while 4 chambers received a diet that included algae at an inclusion rate of 2.5% (ALG). An 8 hour daily cyclic heat stress (24°C to 36°C) was applied to …

Biology And Ecology Of Aedes (Stegomyia) Aegypti In The Northern Chihuahuan Desert, Adam Joseph Vera

Open Access Theses & Dissertations

Aedes aegypti is a medically important mosquito species that transmits multiple arboviruses, including dengue, chikungunya, Zika, and yellow fever. This mosquito species has expanded its geographical range into expanded into the Northern Chihuahuan Desert to further increase the risk of infection by these viruses in naïve human populations. Although Ae. aegypti is abundant along the U.S.â??Mexico border, the biology and ecology of this mosquito species in this temperate/arid climate region is not understood. The objective of this study was to understand the environmental factors that influence the invasive species of Ae. aegypti abundance, breeding habitat selection, host feeding behavior, and …

Defining The Role Of Core Histones In Cellular Quiescence, Eric M. Small

Biomedical Sciences ETDs

Quiescence is a distinct cell cycle phase, termed G0, in which growth, transcriptional and translational activity, and replication are halted. Importantly, quiescent cells are viable and can return to the cell cycle. Quiescence is a feature of all organisms and a key hallmark of stem cells; however, the regulation of quiescence is still poorly understood.

Prior studies have implicated chromatin in the regulation of quiescence. In aim 1 I conducted a comprehensive screen of H3 and H4 histone mutants to identify chromatin features that may affect quiescence. I identified several histone residues implicated in transcriptional regulation that altered quiescence and …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

The Conquest Of Milk: The Rise Of Lactase Persistence And The Fall Of Scandinavian Hunter-Gatherers, Nicholas Mays

James Madison Undergraduate Research Journal (JMURJ)

Over half of the global human population suffers from lactase nonpersistence, a condition marked by losing the ability to digest lactose after infancy. However, a minority of the global population, primarily located in Central and Northern Europe, has a genetic mutation that results in lactase persistence, which is the continued ability to process lactose after infancy. This interdisciplinary analysis blends archaeology, cultural anthropology, evolutionary biology, and archaeogenetics to explore the origin and rise of lactase persistence in Europe and its contribution to the end of hunter-gatherer societies in Scandinavia. Furthermore, the paper uses gene-culture coevolutionary theory to argue that lactase …

A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang

Biology Faculty Publications

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from …

Unraveling The Complex Interactions Between Members Of The Schistosoma Haematobium Group And Bulinus Snails In And Around Lake Victoria In West Kenya, Caitlin Raiselle Babbitt

Biology ETDs

Schistosoma haematobium, the agent of urogenital schistosomiasis, and related schistosomes are transmitted by members of the genus Bulinus. Each of the 38 Bulinus species vary in their ability to vector schistosome species and non-schistosome trematodes resulting in a patchwork of snail-parasite compatibilities. Accurately identifying snail intermediate hosts and the disease-causing parasites they transmit is critical for snail control strategies and the management of human schistosomiasis. Towards these ends, this thesis identifies bulinid species and the parasites they transmit and implicates certain species in the transmission of S. haematobium. The thesis also includes a systematic review of methods …

Cell Size Control Mechanisms In The Multiple Fission Cell Cycle Of Chlamydomonas, Dianyi Liu

Dissertations

Size homeostasis is achieved by a balance between cell growth and cell division, but the underlying mechanisms are yet fully understood. Green alga Chlamydomonas reinhardtii (Chlamydomonas) is a unique model for size control. Instead of the canonical binary fission cell cycle, Chlamydomonas uses a multiple fission cell cycle where a prolonged G1 phase is followed by rapid alternative n rounds of S/M (DNA synthesis and mitosis) cycles to produce 2ⁿ daughter cells. Two size checkpoints show size-dependence: the Commitment checkpoint governs a minimum size for a cell to divide at least once, and the S/M checkpoint governs the division …

Identification Of Quantitative Trait Loci (Qtls) For Resistance To Bacterial Leaf Streak: Xanthomonas Translucens Using Qtl And Association Mapping In Three Populations Of Soft Red Winter Wheat, Benjamin Tyler Meritt

LSU Doctoral Dissertations

Bacterial leaf streak (BLS) and black chaff, caused by Xanthomonas translucens pv. undulosa (Xtu), can be a very destructive disease of wheat, especially in the warmer, wetter areas of the Southeastern U.S. Yield losses of up to 40 percent have been recorded in some cases in southern wheat growing regions. With no effective agronomic or chemical method of disease control, identification of genetic resistance is seen as a promising solution. Three soft red winter wheat populations (GAWN, ARK-SNP, and AGS 2060- AGS 2035 DH) representative of soft red winter wheat germplasm in the southeastern U.S. developed by …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Lord Of The Z-Rings: Uncovering The Role Of Mraz And Ftsl In Bacillus Subtilis Cell Division, Maria Louise White

USF Tampa Graduate Theses and Dissertations

Cell division is a complex and highly orchestrated process that requires careful coordination. The process of cell division in prokaryotes primarily occurs via binary fission, where one mother cell becomes two genetically identically and equally sized daughter cells. In most bacteria a key protein, FtsZ, forms a FtsZ ring (Z-ring) to mark the division site and recruit proteins involved in cytokinesis. Whilst much has been learned about the contents and assembly of the divisome in model organisms such as Escherichia coli and Bacillus subtilis factors governing the regulation of divisome are much more poorly understood. …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …

Analysis Of Phenotypic Expression Associated With Different Genotypes Of The Blue/Brown Eyes Single Nucleotide Polymorphism, Jade Riddle, Taylor Mckinney

Fall Showcase for Research and Creative Inquiry

No abstract provided.

The Genetics Of Skin Cancer: What Genes Drive The Development Of Basal Cell Carcinoma, Squamous Cell Carcinoma, And Melanoma?, Cassandra Poole, Abagail Pack, Elizabeth Whitehead, Virginia Marshall

Fall Showcase for Research and Creative Inquiry

Skin cancer is one of the most common forms of cancer worldwide. The American Academy of Dermatology estimates that 9500 people in the United States are diagnosed with skin cancer every day, and that 1 in 5 Americans will be diagnosed with skin cancer by age 70. With such a high prevalence of disease, understanding how skin cancer develops and how it can be treated is extremely important. This project aims to analyze the genes involved in the development of the three most common forms of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma.

Tree To Tree: Phylogenetics Of Diverse Anura Using Portable Lab Equipment: Primer Optimization, Bioinformatic Pipeline, And Phylogenetic Analyses Reveal Potential New Species And Ability To Identify Evolutionary Relationships In A Hyper Diverse Anura Clade Using Nanopore Sequencing, Elinor Sterner

Independent Study Project (ISP) Collection

The Corredor Llanganates-Sangay is an extremely significant region for conservation, coined a “gift to the earth” by the World Wildlife Fund. Understanding amphibians species and populations is key due to their roles as hyper sensitive bioindicators. In recent years, portable sequencing equipment (Mini PCR thermocyclers, Oxford Nanopore Technology’s MinION sequencer, etc) make genetic data collection in remote areas possible, greatly increasing potential for conservation genetics and genomics. This study uses portable equipment to sequence two mitochondrial loci in 104 Anuran samples collected in four sites in the Corridor and presents phylogenies of each gene as well as a concatenated phylogeny. …

Leaf Phenology And Freeze Tolerance Of The Invasive Tree Pyrus Calleryana (Roseaceae) And Potential Native Competitors, Margaret E. Maloney, Abby Hay, Eric B. Borth, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana is one of the most problematic invasive species in the eastern United States. The mechanisms that enable Py. calleryana to establish and outcompete native plants are not fully understood but likely include a profile of advantageous traits. Extended leaf phenology is a characteristic noted in many woody invasive plants. Leaf phenology of Py. calleryana and two native woody species, Populus deltoides and Platanus occidentalis, was observed in natural areas near Dayton, OH from December 2019 to November 2020. A frost event in May also gave us the serendipitous opportunity to assess frost tolerance of these species. We …

Leveraging Family History In Genetic Association Analyses Of Binary Traits, Yixin Zhang, James B Meigs, Ching-Ti Liu, Josée Dupuis, Chloé Sarnowski

Faculty, Staff and Student Publications

BACKGROUND: Considering relatives' health history in logistic regression for case-control genome-wide association studies (CC-GWAS) may provide new information that increases accuracy and power to detect disease associated genetic variants. We conducted simulations and analyzed type 2 diabetes (T2D) data from the Framingham Heart Study (FHS) to compare two methods, liability threshold model conditional on both case-control status and family history (LT-FH) and Fam-meta, which incorporate family history into CC-GWAS.

RESULTS: In our simulation scenario of trait with modest T2D heritability (h

CONCLUSIONS: Overall, LT-FH and Fam-meta had higher power than CC-GWAS in simulations, especially using phenotypes that were more prevalent …

Development And Characterization Of Type I Interferon Receptor Knockout Sheep: A Model For Viral Immunology And Reproductive Signaling, Christopher J. Davies, Zhiqiang Fan, Kira P. Morgado, Ying Liu, Misha Regouski, Qinggang Meng, Aaron J. Thomas, Sang-Im Yun, Byung-Hak Song, Jordan C. Frank, Iuri V. Perisse, Arnaud Van Wettere, Young-Min Lee, Irina A. Polejaeva

Animal, Dairy, and Veterinary Science Faculty Publications

Type I interferons (IFNs) initiate immune responses to viral infections. Their effects are mediated by the type I IFN receptor, IFNAR, comprised of two subunits: IFNAR1 and IFNAR2. One or both chains of the sheep IFNAR were disrupted in fetal fibroblast lines using CRISPR/Cas9 and 12 lambs were produced by somatic cell nuclear transfer (SCNT). Quantitative reverse transcription-polymerase chain reaction for IFN-stimulated gene expression showed that IFNAR deficient sheep fail to respond to IFN-alpha. Furthermore, fibroblast cells from an IFNAR2^−/− fetus supported significantly higher levels of Zika virus (ZIKV) replication than wild-type fetal fibroblast cells. Although many lambs have …

Neural And Cardiac Mechanisms In Friedreich's Ataxia With Patient-Derived Ipscs, Mariana Burgos Angulo

USF Tampa Graduate Theses and Dissertations

Friedreich's ataxia (FA) is an autosomal recessive disease caused, in most cases, by a GAA trinucleotide repeat expansion in the first intron of the frataxin (FXN) gene, which results in transcriptional repression of the encoded protein frataxin. FA is a progressive neurodegenerative disorder, but the primary cause of death is hypertrophic cardiomyopathy, which occurs in 60% of the patients. Several functions of frataxin have been proposed, but none of them can fully explain why its deficiency causes the FA phenotypes nor why the most affected cell types are neurons and cardiomyocytes. It is possible that frataxin affects neural and cardiac …

Heterogeneity In The Prevalence Of Premature Hypertension Among Asian American Populations Compared With White Individuals: A National Health Interview Survey Study, Sina Kianoush, Mahmoud Al Rifai, Anwar T. Merchant, Xiaoming Jia, Zainab Samad, Aneil Bhalla, Ayesha Khan, Dongshan Zhu, Salim S. Virani

Section of Cardiology

Background: Differences in prevalence of risk factors such as hypertension may explain heterogeneity in cardiovascular risk across Asian American populations.
Methods: We used National Health Interview Survey (NHIS) data from 2006 to 2018 among White, Chinese, Asian Indian, Filipino, and 'other Asians' (Japanese, Korean, and Vietnamese). Unadjusted and adjusted odds ratios (aOR) with 95% confidence intervals were reported using logistic regression models for the association between race and self-reported premature hypertension (age old). Models were adjusted for sex, education, body mass index, smoking status, diabetes, and coronary heart disease.
Results: We studied 99,864 participants with history of hypertension (mean age, …

Genetic Loci And Prioritization Of Genes For Kidney Function Decline Derived From A Meta-Analysis Of 62 Longitudinal Genome-Wide Association Studies, Mathias Gorski, Humaira Rasheed, Alexander Teumer, Laurent F Thomas, Sarah E Graham, Gardar Sveinbjornsson, Thomas W Winkler, Felix Günther, Klaus J Stark, Jin-Fang Chai, Bamidele O Tayo, Matthias Wuttke, Yong Li, Adrienne Tin, Tarunveer S Ahluwalia, Johan Ärnlöv, Bjørn Olav Åsvold, Stephan J L Bakker, Bernhard Banas, Nisha Bansal, Mary L Biggs, Ginevra Biino, Michael Böhnke, Eric Boerwinkle, Erwin P Bottinger, Hermann Brenner, Ben Brumpton, Robert J Carroll, Layal Chaker, John Chalmers, Miao-Li Chee, Miao-Ling Chee, Ching-Yu Cheng, Audrey Y Chu, Marina Ciullo, Massimiliano Cocca, James P Cook, Josef Coresh, Daniele Cusi, Martin H De Borst, Frauke Degenhardt, Kai-Uwe Eckardt, Karlhans Endlich, Michele K Evans, Mary F Feitosa, Andre Franke, Sandra Freitag-Wolf, Christian Fuchsberger, Piyush Gampawar, Ron T Gansevoort, Mohsen Ghanbari, Sahar Ghasemi, Vilmantas Giedraitis, Christian Gieger, Daniel F Gudbjartsson, Stein Hallan, Pavel Hamet, Asahi Hishida, Kevin Ho, Edith Hofer, Bernd Holleczek, Hilma Holm, Anselm Hoppmann, Katrin Horn, Nina Hutri-Kähönen, Kristian Hveem, Shih-Jen Hwang, M Arfan Ikram, Navya Shilpa Josyula, Bettina Jung, Mika Kähönen, Irma Karabegović, Chiea-Chuen Khor, Wolfgang Koenig, Holly Kramer, Bernhard K Krämer, Brigitte Kühnel, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Terho Lehtimäki, Man Li, Wolfgang Lieb, Lifelines Cohort Study, Lars Lind, Cecilia M Lindgren, Ruth J F Loos, Mary Ann Lukas, Leo-Pekka Lyytikäinen, Anubha Mahajan, Pamela R Matias-Garcia, Christa Meisinger, Thomas Meitinger, Olle Melander, Yuri Milaneschi, Pashupati P Mishra, Nina Mononen, Andrew P Morris, Josyf C Mychaleckyj, Girish N Nadkarni, Mariko Naito, Masahiro Nakatochi, Mike A Nalls, Matthias Nauck, Kjell Nikus, Boting Ning, Ilja M Nolte, Teresa Nutile, Michelle L O'Donoghue, Jeffrey O'Connell, Isleifur Olafsson, Marju Orho-Melander, Afshin Parsa, Sarah A Pendergrass, Brenda W J H Penninx, Mario Pirastu, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Myriam Rheinberger, Kenneth M Rice, Federica Rizzi, Alexander R Rosenkranz, Peter Rossing, Jerome I Rotter, Daniela Ruggiero, Kathleen A Ryan, Charumathi Sabanayagam, Erika Salvi, Helena Schmidt, Reinhold Schmidt, Markus Scholz, Ben Schöttker, Christina-Alexandra Schulz, Sanaz Sedaghat, Christian M Shaffer, Karsten B Sieber, Xueling Sim, Mario Sims, Harold Snieder, Kira J Stanzick, Unnur Thorsteinsdottir, Hannah Stocker, Konstantin Strauch, Heather M Stringham, Patrick Sulem, Silke Szymczak, Kent D Taylor, Chris H L Thio, Johanne Tremblay, Simona Vaccargiu, Pim Van Der Harst, Peter J Van Der Most, Niek Verweij, Uwe Völker, Kenji Wakai, Melanie Waldenberger, Lars Wallentin, Stefan Wallner, Judy Wang, Dawn M Waterworth, Harvey D White, Cristen J Willer, Tien-Yin Wong, Mark Woodward, Qiong Yang, Laura M Yerges-Armstrong, Martina Zimmermann, Alan B Zonderman, Tobias Bergler, Kari Stefansson, Carsten A Böger, Cristian Pattaro, Anna Köttgen, Florian Kronenberg, Iris M Heid

Faculty, Staff and Student Publications

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine …

Cell-Intrinsic Melanin Fails To Protect Melanocytes From Ultraviolet-Mutagenesis In The Absence Of Epidermal Melanin, Tirzah J. Weiss, Emma R. Crawford, Valentina Posada, Hafeez Rahman, Tong Liu, Brandon M. Murphy, Tiffany E. Arnold, Shannon Gray, Zhexuan Hu, Rebecca C. Hennessey, Lianbo Yu, John August D'Orazio, Craig J. Burd, Jonathan H. Zippin, Douglas Grossman, Christin E. Burd

Markey Cancer Center Faculty Publications

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB- sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) …