Genetics and Genomics Commons^™

Bottom-Up Drivers Of Future Fire Regimes In Western Boreal North America, Adrianna C. Foster, Jacquelyn K. Shuman, Brendan M. Rogers, Xanthe J. Walker, Michelle C. Mack, Laura L. Bourgeau-Chavez, Sander Veraverbeke, Scott J. Goetz

Aspen Bibliography

Forest characteristics, structure, and dynamics within the North American boreal region are heavily influenced by wildfire intensity, severity, and frequency. Increasing temperatures are likely to result in drier conditions and longer fire seasons, potentially leading to more intense and frequent fires. However, an increase in deciduous forest cover is also predicted across the region, potentially decreasing flammability. In this study, we use an individual tree-based forest model to test bottom-up (i.e. fuels) vs top-down (i.e. climate) controls on fire activity and project future forest and wildfire dynamics. The University of Virginia Forest Model Enhanced is an individual tree-based forest model …

A Crispr Toolbox For Generating Intersectional Genetic Mouse Models For Functional, Molecular, And Anatomical Circuit Mapping, Savannah J Lusk, Andrew Mckinney, Patrick J Hunt, Paul G Fahey, Jay Patel, Andersen Chang, Jenny J Sun, Vena K Martinez, Ping Jun Zhu, Jeremy R Egbert, Genevera Allen, Xiaolong Jiang, Benjamin R Arenkiel, Andreas S Tolias, Mauro Costa-Mattioli, Russell S Ray

Faculty, Staff and Students Publications

BACKGROUND: The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of …

Genetic Parameters, Heterosis, And Breed Effects For Body Condition Score And Mature Cow Weight In Beef Cattle, André Mauric F. Ribeiro, Leticia P. Sanglard, Warren M. Snelling, R. Mark Thallman, Larry A. Kuehn, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Understanding the genetic relationship between mature cow weight (MWT) and body condition score (BCS) is useful to implement selection programs focused on cow efficiency. The objectives of this study were to estimate genetic parameters, heterosis, and breed effects for MWT and BCS. In total, 25,035 and 24,522 overlapping records were available for MWT and BCS on 6,138 and 6,131 cows, respectively, from the Germplasm Evaluation program, a crossbred beef population at the U.S. Meat Animal Research Center. Pedigree was available for 48,013 individuals. Univariate animal models were used to estimate heritabilities for each trait by parity. …

The Earth Biogenome Project 2020: Starting The Clock, Harris A. Lewin, Stephen Richards, Erez Lieberman Aiden, Miguel L. Allende, John M. Archibald, Katharine B. Baker, Bridget Baumgartner, Katherine Belov, Giorgio Bertorelle, Mark L. Blaxter, Jing Cai, Nicolette D. Caperello, Keith Carlson, Juan Carlos Castilla-Rubio, Shu-Miaw Chaw, Lei Chen, Anna K. Childers, Jonathan A. Coddington, Dalia A. Conde, Montserrat Corominas, Keith A. Crandall, Andrew J. Crawford, Federica Dipalma, Richard Durbin, Thankgod E. Ebenezer, Scott V. Edwards, Olivier Fedrigo, Paul Flicek, Giulio Formenti, Richard A. Gibbs, M. Thomas P. Gilbert, Melissa M. Goldstein, Jennifer Marshall Graves, Henry T. Greely, Igor V. Grigoriev, Kevin J. Hackett, Neil Hall, David Haussler, Kristofer M. Helgen, Carolyn J. Hogg, Sachiko Isobe, Kjetill Sigurd Jakobson, Axel Janke, Erich D. Jarvis, Warren E. Johnson, Steven J. M. Jones, Elinor K. Karlsson, Paul J. Kersey, Jin-Hyoung Kim, W. John Kress, Shigehiro Kuraku, Mara K. N. Lawniczak, James H. Leebens-Mack, Xueyan Li, Kerstin Lindblad-Toh, Xin Liu, Jose V. Lopez, Tomas Marques-Bonet, Sophie Mazard, Jonna A. K. Mazet, Camila J. Mazzoni, Eugene W. Myers, Rachel J. O'Neill, Sadye Paez, Hyun Park, Gene E. Robinson, Cristina Roquet, Oliver A. Ryder, Jamal S. M. Sabir, H. Bradley Shaffer, Timothy M. Shank, Jacob S. Sherkow, Pamela S. Soltis, Boping Tang, Leho Tedersoo, Marcela Uliano-Silva, Kun Wang, Xiaofeng Wei, Regina Wetzer, Julia L. Wilson, Xun Xu, Huanming Yang, Anne D. Yoder, Guojie Zhang

Biology Faculty Articles

No abstract provided.

Standards Recommendations For The Earth Biogenome Project, Mara K. Lawniczak, Richard Durbin, Paul Flicek, Kerstin Lindblad-Toh, Xiaofeng Wei, John M. Archibald, William J. Baker, Katherine Belov, Mark L. Blaxter, Tomas Marques-Bonet, Anna K. Childers, Jonathan A. Coddington, Keith A. Crandall, Andrew J. Crawford, Robert P. Davey, Federica Di Palma, Qi Fang, Wilfried Haerty, Neil Hall, Katherine J. Hoff, Kerstin Howe, Erich D. Jarvis, Warren E. Johnson, Rebecca N. Johnson, Paul J. Kersey, Xin Liu, Jose V. Lopez, Eugene W. Myers, Olga Vinnere Pettersson, Adam M. Phillippy, Monica F. Poelchau, Kim D. Pruitt, Arang Rhie, Juan Carlos Castilla-Rubio, Sunil Kumar Sahu, Nicholas A. Salmon, Pamela S. Soltis, David Swarbreck, Françoise Thibaud-Nissen, Sibo Wang, Jill L. Wegrzyn, Guojie Zhang, He Zhang, Harris A. Lewin, Stephen Richards

Biology Faculty Articles

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. …

Why Sequence All Eukaryotes?, Mark Blaxter, John M. Archibald, Anna K. Childers, Jonathan A. Coddington, Keith A. Crandall, Federica Di Palma, Richard Durbin, Scott V. Edwards, Jennifer A.M. Graves, Kevin J. Hackett, Neil Hall, Erich D. Jarvis, Rebecca N. Johnson, Elinor K. Karlsson, W. John Kress, Shigehiro Kuraku, Mara K. N. Lawniczak, Kerstin Lindblad-Toh, Jose V. Lopez, Nancy A. Moran, Gene E. Robinson, Oliver A. Ryder, Beth Shapiro, Pamela S. Soltis, Tandy Warnow, Guojie Zhang, Harris A. Lewin

Biology Faculty Articles

Life on Earth has evolved from initial simplicity to the astounding complexity we experience today. Bacteria and archaea have largely excelled in metabolic diversification, but eukaryotes additionally display abundant morphological innovation. How have these innovations come about and what constraints are there on the origins of novelty and the continuing maintenance of biodiversity on Earth? The history of life and the code for the working parts of cells and systems are written in the genome. The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes—about 2 million species—should be sequenced to high quality to produce a …

Data-Driven Modeling Predicts Gene Regulatory Network Dynamics During The Differentiation Of Multipotential Hematopoietic Progenitors, Joanna Handzlik, Manu

Biology Faculty Publications

Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. Here, we utilize transient gene expression patterns to infer the genetic architecture—the type and strength of regulatory interconnections—and dynamics of a twelve-gene GRN including key TFs and cytokine receptors. We trained gene circuits, dynamical models that learn genetic architecture, on high temporal-resolution gene-expression data from the …

Identifying Conifer Tree Vs. Deciduous Shrub And Tree Regeneration Trajectories In A Space-For-Time Boreal Peatland Fire Chronosequence Using Multispectral Lidar, Humaira Enayetullah, Laura Chasmer, Christopher Hopkinson, Dan Thompson, Danielle Cobbaert

Aspen Bibliography

Wildland fires and anthropogenic disturbances can cause changes in vegetation species composition and structure in boreal peatlands. These could potentially alter regeneration trajectories following severe fire or through cumulative impacts of climate-mediated drying, fire, and/or anthropogenic disturbance. We used lidar-derived point cloud metrics, and site-specific locational attributes to assess trajectories of post-disturbance vegetation regeneration in boreal peatlands south of Fort McMurray, Alberta, Canada using a space-for-time-chronosequence. The objectives were to (a) develop methods to identify conifer trees vs. deciduous shrubs and trees using multi-spectral lidar data, (b) quantify the proportional coverage of shrubs and trees to determine environmental conditions driving …

Chromomap: An R Package For Interactive Visualization Of Multi-Omics Data And Annotation Of Chromosomes, Lakshay Anand, Carlos M. Rodriguez Lopez

Horticulture Faculty Publications

BACKGROUND: The recent advancements in high-throughput sequencing have resulted in the availability of annotated genomes, as well as of multi-omics data for many living organisms. This has increased the need for graphic tools that allow the concurrent visualization of genomes and feature-associated multi-omics data on single publication-ready plots.

RESULTS: We present chromoMap, an R package, developed for the construction of interactive visualizations of chromosomes/chromosomal regions, mapping of any chromosomal feature with known coordinates (i.e., protein coding genes, transposable elements, non-coding RNAs, microsatellites, etc.), and chromosomal regional characteristics (i.e. genomic feature density, gene expression, DNA methylation, chromatin modifications, etc.) of organisms …

Mutations In Hcfc1 And Ronin Result In An Inborn Error Of Cobalamin Metabolism And Ribosomopathy, Tiffany Chern, Annita Achilleos, Xuefei Tong, Matthew C Hill, Alexander B Saltzman, Lucas C Reineke, Arindam Chaudhury, Swapan K Dasgupta, Yushi Redhead, David Watkins, Joel R Neilson, Perumal Thiagarajan, Jeremy B A Green, Anna Malovannaya, James F Martin, David S Rosenblatt, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss of Mmachc, metabolic perturbations, and developmental defects previously …

Rare Coding Variants In 35 Genes Associate With Circulating Lipid Levels-A Multi-Ancestry Analysis Of 170,000 Exomes, George Hindy, Peter Dornbos, Mark D Chaffin, Dajiang J Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A Aguilar-Salinas, Lucinda Antonacci-Fulton, Diego Ardissino, Donna K Arnett, Stella Aslibekyan, Gil Atzmon, Christie M Ballantyne, Francisco Barajas-Olmos, Nir Barzilai, Lewis C Becker, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Lori L Bonnycastle, Erwin Bottinger, Donald W Bowden, Matthew J Bown, Jennifer A Brody, Jai G Broome, Noël P Burtt, Brian E Cade, Federico Centeno-Cruz, Edmund Chan, Yi-Cheng Chang, Yii-Der I Chen, Ching-Yu Cheng, Won Jung Choi, Rajiv Chowdhury, Cecilia Contreras-Cubas, Emilio J Córdova, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, John Danesh, Paul S De Vries, Ralph A Defronzo, Harsha Doddapaneni, Ravindranath Duggirala, Susan K Dutcher, Patrick T Ellinor, Leslie S Emery, Jose C Florez, Myriam Fornage, Barry I Freedman, Valentin Fuster, Ma Eugenia Garay-Sevilla, Humberto García-Ortiz, Soren Germer, Richard A Gibbs, Christian Gieger, Benjamin Glaser, Clicerio Gonzalez, Maria Elena Gonzalez-Villalpando, Mariaelisa Graff, Sarah E Graham, Niels Grarup, Leif C Groop, Xiuqing Guo, Namrata Gupta, Sohee Han, Craig L Hanis, Torben Hansen, Jiang He, Nancy L Heard-Costa, Yi-Jen Hung, Mi Yeong Hwang, Marguerite R Irvin, Sergio Islas-Andrade, Gail P Jarvik, Hyun Min Kang, Sharon L R Kardia, Tanika Kelly, Eimear E Kenny, Alyna T Khan, Bong-Jo Kim, Ryan W Kim, Young Jin Kim, Heikki A Koistinen, Charles Kooperberg, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Leslie A Lange, Jiwon Lee, Juyoung Lee, Seonwook Lee, Donna M Lehman, Rozenn N Lemaitre, Allan Linneberg, Jianjun Liu, Ruth J F Loos, Steven A Lubitz, Valeriya Lyssenko, Ronald C W Ma, Lisa Warsinger Martin, Angélica Martínez-Hernández, Rasika A Mathias, Stephen T Mcgarvey, Ruth Mcpherson, James B Meigs, Thomas Meitinger, Olle Melander, Elvia Mendoza-Caamal, Ginger A Metcalf, Xuenan Mi, Karen L Mohlke, May E Montasser, Jee-Young Moon, Hortensia Moreno-Macías, Alanna C Morrison, Donna M Muzny, Sarah C Nelson, Peter M Nilsson, Jeffrey R O'Connell, Marju Orho-Melander, Lorena Orozco, Colin N A Palmer, Nicholette D Palmer, Cheol Joo Park, Kyong Soo Park, Oluf Pedersen, Juan M Peralta, Patricia A Peyser, Wendy S Post, Michael Preuss, Bruce M Psaty, Qibin Qi, D C Rao, Susan Redline, Alexander P Reiner, Cristina Revilla-Monsalve, Stephen S Rich, Nilesh Samani, Heribert Schunkert, Claudia Schurmann, Daekwan Seo, Jeong-Sun Seo, Xueling Sim, Rob Sladek, Kerrin S Small, Wing Yee So, Adrienne M Stilp, E Shyong Tai, Claudia H T Tam, Kent D Taylor, Yik Ying Teo, Farook Thameem, Brian Tomlinson, Michael Y Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Teresa Tusié-Luna, Miriam S Udler, Rob M Van Dam, Ramachandran S Vasan, Karine A Viaud Martinez, Fei Fei Wang, Xuzhi Wang, Hugh Watkins, Daniel E Weeks, James G Wilson, Daniel R Witte, Tien-Yin Wong, Lisa R Yanek, Amp-T2d-Genes, Myocardial Infarction Genetics Consortium, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Nhlbi Topmed Lipids Working Group, Sekar Kathiresan, Daniel J Rader, Jerome I Rotter, Michael Boehnke, Mark I Mccarthy, Cristen J Willer, Pradeep Natarajan, Jason A Flannick, Amit V Khera, Gina M Peloso

Faculty, Staff and Student Publications

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, …

Clinical Performance Of The Xpert® Ct/Ng Test For Detection Of Chlamydia Trachomatis And Neisseria Gonorrhoeae: A Multicenter Evaluation In Chinese Urban Hospitals, Fred C. Tenover, Yan Han, Mei-Qin Shi, Qing-Ping Jiang, Wen-Jing Le, Xiao-Lin Qin, Han-Zhen Xiong, He-Ping Zheng, Yi-Wei Tang, Yue-Ping Yin

Biology Faculty Publications

Background: We aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China.

Methods: This study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis.

Results: In this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were …

Design Of A Synthetic Temperature-Activated Epigenetic Biocontainment System, Owen Rivers Page

Theses and Dissertations

The need for an internal control to govern engineered strain survival is becoming apparent when considering the biosafety and ethics within biotechnological research. Using understudied regulatory elements known as RNA thermometers (RNATs) that can modulate protein translation based on temperature changes and a Type II restriction modification system, we posit the creation of a synthetic temperature-activated epigenetic biocontainment system, termed the ‘sentinel switch’. We have mined a wide variety of bacteria from Yersinia pestis to Synechocystis sp. looking for novel RNATs. A complementary synthetic biology approach based on library generation and screening of chimeric RNATs (ChRNATs) was also conducted. RNATs …

The Drosophila Mutagen-Sensitivity Gene Mus109 Encodes Dmdna2, Chandani Mitchell, Vada Becker, Jordan Deloach, Erica Nestore, Elyse Bolterstein, Kathryn P. Kohl

Biology Faculty Publications

The development of gene mapping techniques has a long and storied history in the Drosophila melanogaster model system (reviewed in [1]), beginning with Alfred Sturtevant’s fundamental publication of the first genetic map in 1913 [2]. In this work, Sturtevant showed that genes are arranged in a linear order along chromosomes and that the recombination frequency between two genes could be used as a measure of the distance between them. This discovery created the foundation for other key advances in Drosophila gene mapping, including the generation of detailed polytene chromosome cytogenetic maps [3,4], the development of deletion kits covering the genome …

Cross Species Use Of Human Microarray Genotyping Technology For Bornean Orangutan (Pongo Pygmaeus) Snp Discovery, Ruth Ella Linsky, R. Steven Wagner, Reniastoetie Djojoasmoro, Joseph G. Lorenz, Biruté M. F. Galdikas

Student Published Works

Previous genetic studies of orangutans (Pongo spp.) have relied mainly upon mitochondrial DNA or microsatellite short tandem repeats (STR) for genomic genotyping analysis. Scientists have yet to take advantage of the genetic closeness of the great apes to humans for genomic analysis by using advanced techniques available for human genotyping. To genotype orangutans at Tanjung Puting National Park, we developed a novel combination of a methyl-based magnetic enrichment capture of genomic fecal DNA with genotyping on a human targeted single nucleotide polymorphism (SNP) microarray, and compared this to additional microsatellite (STR) micro-capillary genotyping. We successfully isolated 125 known human genomic …

Cbp60-Db: An Alphafold-Predicted Plant Kingdom-Wide Database Of The Calmodulin-Binding Protein 60 (Cbp60) Protein Family With A Novel Structural Clustering Algorithm, Keaun Amani, Vanessa Shivnauth, Christian Castroverde

Biology Faculty Publications

Molecular genetic analyses in the model species Arabidopsis thaliana have demonstrated the major roles of different CAM-BINDING PROTEIN 60 (CBP60) proteins in growth, stress signaling, and immune responses. Prominently, CBP60g and SARD1 are paralogous CBP60 transcription factors that regulate numerous components of the immune system, such as cell surface and intracellular immune receptors, MAP kinases, WRKY transcription factors, and biosynthetic enzymes for immunity-activating metabolites salicylic acid (SA) and N-hydroxypipecolic acid (NHP). However, their function, regulation and diversification in most species remain unclear. Here we have created CBP60-DB, a structural and bioinformatic database that comprehensively characterized 1052 CBP60 gene homologs …

Characterization Of Cofilin And Its Potential Role In The Epha4 Pathway, Brian Donald Condron

Master's Theses and Doctoral Dissertations

EphA4 is a receptor tyrosine kinase that is responsible for cellular adhesion and locomotion using repulsion signaling in early development of Xenopus laevis. EphA4 regulates cellular locomotion by controlling proteins within its signal transduction pathway, which may include the protein cofilin. Cofilin actively severs and removes actin monomers, thus altering the actin cytoskeleton, leading to the cessation of cellular crawl. During the gastrulation phase of embryonic development, individual cells are relocating to create the three primary germ layers of the organism. Failure of this process to occur results in attrition of the embryos, frequently by way of embryonic exogastrulation. …

Investigating Replacement Of A Yeast Gene With A Human Gene As A Rare Disease Model System, Emma Pastoor, Amy Wilstermann, Rachael Baker

Summer Research

• BCS1L is a mitochondrial protein that assists in building complex III of the electron transport chain which allows for cellular respiration to occur
• Different mutations in BCS1L can result in three rare genetic diseases: Bjornstad Syndrome, BCS1L Mitopathy, or GRACILE Syndrome

Altered Gene Expression In Response To Chronic Cardiac Sarcomere Modifications, Oula Salih, Emily Lavey, Margaret Westfall

Summer Research

No abstract provided.

Development And Preliminary Testing Of A Walkassist Device With Dynamic Support, Simon Detmer, Gita Regmi, Kaitlyn Boellner, Ann Reinthal, Hanz Richter

Summer Research

In the past decade, usage of walking aids in the senior population has increased by 50 percent and is expected to double by 20501 . Walkers are used as a temporary aid to encourage mobility after surgery or fracture, but they often become permanent aids2 . In the United States, about 12 percent of the elderly population use walkers1. Walkers are prescribed to reduce the load on lower limbs and/or to improve balance and stability. However, longer usage of walkers leads to low physical function and low self-confidence. Walker users typically have forward leaning posture due to load transfer from …

Comparative Evaluation Of Assemblers For Metagenomic Data Analysis, Matheus Pavini Franco Ferreira

Honors Undergraduate Theses

Metagenomics is a cultivation-independent approach for obtaining the genomic composition of microbial communities. Microbial communities are ubiquitous in nature. Microbes which are associated with the human body play important roles in human health and disease. These roles span from protecting us against infections from other bacteria, to being the causes of these diseases. A deeper understanding of these communities and how they function inside our bodies allows for advancements in treatments and preventions for these diseases. Recent developments in metagenomics have been driven by the emergence of Next-Generation Sequencing technologies and Third-Generation Sequencing technologies that have enabled cost-effective DNA sequencing …

Whole Exome Sequencing Identifies A Novel Mutation In Aspm And Ultra-Rare Mutation In Cdk5rap2 Causing Primary Microcephaly In Consanguineous Pakistani Families, Ehtisham Ul Haq Makhdoom, Haseeb Anwar, Shahid Mahmood Baig, Ghulam Hussain

Department of Biological & Biomedical Sciences

Background & objectives: Primary Microcephaly (MCPH) is a rare neurogenetic disease, manifesting congenitally reduced head circumference and non-progressive intellectual disability (ID). To date, twenty-eight genes with biallelic mutations have been reported for this disorder. The study aimed for molecular genetic characterization of Pakistani families segregating MCPH.
Methods: We studied two unrelated consanguineous families (family A and B) presenting >2 patients with diagnostic symptoms of MCPH, born to asymptomatic parents. We employed whole-exome sequencing (WES) of probands to find putative causal mutations. The candidate variants were further confirmed and analyzed for co-segregation by Sanger sequencing of all available members of each …

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV₁, FVC, and FEV₁/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …

Identification Of A Novel Protein Interaction That Elucidates The Mechanism Of Idiopathic Recurrent Miscarriages In Women With Nlrp2 Mutations, Nayeon Son

Graduate Theses/Dissertations

The protein NOD-Like receptor pyrin domain containing 2 (NLRP2) is one member of a larger family of protein receptors that plays an important role in our innate immune system. In humans, the NLR family consists of 22 proteins. However, only about a half of NLRs’ functions are known, but many are pro-inflammatory, causing inflammation. NLRP2 has been identified to be a maternal effect gene regulating early embryo development in idiopathic recurrent miscarriages. In previous studies, mutations in the NLRP2 gene resulted in genetic maternal imprinting disorders due to NLRP2 regulating DNA methylation. However, the exact mechanisms involved in recurrent miscarriages …

Molecular Genetic Investigation Of Twins, Families, And Populations, Jeffrey John Beck

Dissertations and Theses

Twins have long been of interest for illuminating genetic and environmental influences on human traits and diseases. These explorations have been accelerated by the substantial amount of information collected from twins and their families participating in twin registers around the world. In this dissertation, I review what is known and what remains unknown about the biology and genetics of twins and the underlying twinning process. To elucidate additional genetic factors of the twinning process, I employed pedigree-based analysis to identify genetic regions shared among distantly related mothers of dizygotic twins. The shared regions may potentially contain rare genetic variants with …

Single Cell Lineage Tracing Reveals Mechanisms Of Tumor Initiation And Chemoresistance In Small Cell Lung Cancer, Hannah Wollenzien

Dissertations and Theses

Small Cell Lung Cancer (SCLC) is a devastating disease characterized by a very low two-year survival rate and almost universal acquisition of chemoresistance. Nearly all patients have tumors driven by functional inactivation of the tumor suppressors Rb and p53, but despite the uniform origins of this tumor, not all patients are genetically or phenotypically identical. SCLC can be subtyped into four unique molecular subtypes, determined by the expression of ASCL1, NEUROD1, POU2F3, or YAP1. These subtypes are plastic, and subtype switching after chemotherapy has been documented. Without the understanding of how tumor heterogeneity arises, we cannot solve the challenge of …

Computational Methods To Analyze Next-Generation Sequencing Data In Genomics And Metagenomics, Saidi Wang

Electronic Theses and Dissertations, 2020-2023

This thesis focuses on two important computational problems in genomics and metagenomics with the public available next-generation sequencing data. One is about gene regulation, for which we explore how distal regulatory elements may interact with the proximal regulatory elements. The other is about metagenomics, in which we study how to reconstruct bacterial strain genomes from shotgun reads. Studying gene regulation, especially distal gene regulation, is important because regulatory elements, including those in distal regulatory regions, orchestrate when, where and how much a gene is activated under every experimental condition. Their dysfunction results in various types of diseases. Moreover, the current …

Use Of Heterothallic Mat Deletion Strains Of Fusarium Graminearum As Test Mates In Crosses To Evaluate The Genetics Of Pathogenicity And Fitness, Gabdiel Emmanuel Yulfo-Soto

Theses and Dissertations--Plant Pathology

Fusarium Head Blight (FHB), caused by Fusarium graminearum sensu stricto and other members of the F. graminearum species complex (FGSC), is a plant disease that occurs on cereal crops worldwide. FHB causes yield losses not only by reducing grain weight, but also by contaminating the kernels with dangerous trichothecene mycotoxins, especially deoxynivalenol (DON). There is a high degree of genotypic and phenotypic variation among pathogen species and strains, but current FHB risk assessment models and treatments do not account for pathogen diversity. Therefore, it is difficult to predict what will happen if a new, potentially more aggressive variant is introduced, …

Effects Of Sunrise/Sunset Lighting On Corticosterone Levels In Coturnix Quail (Coturnix Coturnix), Hannah M. Feuerborn, Sara K. Orlowski

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Both genetics and environment play important roles in the growth, performance, and overall welfare of poultry species. Current commercial production practices typically do not mimic the natural environmental conditions of ancestral poultry species, specifically lighting. The current study aimed to evaluate the impact of genetics and the effect of sunrise/sunset lighting on the stress response of 4 genetic lines of Coturnix quail. The 4 lines utilized in this study included high stress (H), low stress (L), stress control (R), and Arkansas randombred (A) quail lines. Day old chicks from these lines were placed in one of two environmentally controlled rooms. …

Alternatively Spliced Csf3r In Human Health And Disease, Borwyn A. Wang

Theses and Dissertations

Elevated alternative colony stimulating factor 3 receptor (CSF3R) isoforms are observed in myelodysplastic syndromes (MDS) and other myeloid neoplasms, but their role in driving disease progression has not been fully explained. In this study we report on the role of an MDS-associated splicing factor SRSF2 and its effects on the production of Class III and Class IV CSF3R isoforms and granulopoiesis. Class IV add-back in Csf3r-null mice showed impaired neutrophil differentiation with increased number of CFU-G, which largely consisted of metamyelocytes, while Class III showed greater dysgranulopoiesis accompanied by dysmorphic neutrophils. Alternative CSF3R isoforms were elevated in …