The Open Reading Frame Volume 3, Number 1

September, 2016 Volume 3, Number 1

The 2016 Fall semester began with our highly successful Retreat, held this year at the beautiful Park Alumni Center at North Carolina State University’s Centennial Campus. Many thanks go to Melissa Robbins and Robert Anholt for organizing the retreat, and to Grace Parker and Brandon Baker for acting as Masters of Ceremonies for the social activities. And special thanks to all the faculty, postdoctoral research associates and graduate students from 18 different laboratories in eight Departments and four Colleges who presented their work. This was an excellent introduction to the diversity of research in the Program in Genetics and an opportunity to get to know each other better.

Please join me in welcoming our new graduate students, Aldo Carmona Baez, Khushi Goda, Anna Rogers, Lindsay Simmons and Allison Schloop.

Please also join me in congratulating our latest genetics Ph.D. graduates, Drs. Sarah Cash and William (Bill) Barrington. Sarah’s thesis dissertation on “The Distributions and Dynamics of Medea Selfish Genetic Elements in Red Flour Beetle Populations” was performed in the laboratory of Marcé Lorenzen. Bill’s thesis dissertation on “Individual Variation in Diet Response: Health Effects of Dietary Interventions on Mice with Diverse Genetic Background” was performed in the laboratory of David Threadgill.

Attendees of the Program in Genetics Retreat, Park Alumni Center, August 12, 2016

Congratulations also to Jordan Elainey Bouldin, Alexis Nicole Blum, Haley Rachel McCracken, Andrew Alfred Seaman, Mary-Ann Kaitlyn Stanley, Leslie Dale Stevens, Brook Maya Strickland, Lucas Allen Van Gorder, Beau Randolph White, May 2016 graduating seniors with a B. S. majoring in Genetics.

Finally, congratulations to Drs. Megan Fritz and Beth Dumont. Megan, who did her postdoctoral research with Fred Gould, is now an Assistant Professor in the Department of Entomology, University of Maryland, Baltimore County. Beth, who joined the Program as an Initiative for Biological

Complexity Postdoctoral Fellow and then transitioned to her individual K99/R00 grant under the joint mentorship of Nadia Singh, Matthew Breen and Trudy Mackay, is now an Assistant Professor at The Jackson Laboratory.

We have a busy academic year lined up, with an excellent seminar series featuring alumni speakers, a Distinguished Lecturer Series of student-invited speakers, as well as internal and external speakers.

Trudy Mackay, Program Director

2016 Fall Seminars

All seminars are at 1:30 pm in the Stephens Room, 3503 Thomas Hall unless otherwise noted

August 29: Jason Moore, Departments of Genetics and Biostatistics and Epidemiology, University of Pennsylvania

September 12: Rebecca Yang, Department of Neurobiology, Duke University

September 19: Laurianne Chantal Van Landeghem, Department of Molecular Biomedical Sciences, NC State University

September 26: Sarah Elgin, Department of Biology, Washington University St. Louis Genetics Program Teaching Seminar

October 3: David Remington, Department of Biology, University of North Carolina, Greensboro Genetics Program Alumnus Seminar

October 10: John Schimenti, Departments of Biomedical Sciences and Molecular Biology and Genetics, Cornell University

October 17: Joseph Ecker, Genomic Analysis and Plant Molecular and Cellular Biology Laboratories, The Salk Institute for Biological Studies

October 24: Joan Steitz, Department of Molecular Biophysics and Biochemistry, Yale University Genetics Program Distinguished Lecture Series, Graduate Student Invited Speaker

October 31: Victor Frankenstein, Department of Regenerative Medicine, University of Transylvania

November 7: Dahlia Nielsen, Department of Biological Sciences, NC State University

Dr. Sarah Cash (center) and graduating seniors with a B.S

majoring in Genetics: Jordan Bouldin, Alexis Blum,

Haley McCracken, Andrew Seaman, Mary-Ann

Stanley, Leslie Stevens, Brook Strickland, Lucas Van

Gorder and Beau White.

Dr. Bill Barrington (center, left) and Dr. David

Threadgill (center, right) and friends celebrate Bill’s

thesis defense.

November 14: Harris Lewin, Department of Evolution and Ecology, University of California, Davis

November 21: Adriana San Miguel, Department of Chemical and Biomolecular Engineering, NC State University

November 28: Hans Hofmann, Department of Integrative Biology, University of Texas, Austin Genetics Program Distinguished Lecture Series, Graduate Student Invited Speaker

December 5: Stephen Rich, Department of Public Health Sciences, University of Virginia

Upcoming Events

December 9, 2016: Genetics Program Holiday Party, Stephens Room, 3503 Thomas Hall, 11 am – 3 pm. Featuring potluck luncheon, the Genetics themed Performance Contest, Laboratory Ornament Contest, and Holiday Pet Photo Slideshow. More details to come!

February 16-18, 2017: Genetics graduate student recruitment weekend

February 17, 2017: Genetics Graduate Student Annual Symposium

Honors and Awards

Jose Alonso has been named, for the third year in a row, as one of Thomson Reuters 2016 World’s Most Influential Scientific Minds in Plant and Animal Science

Robert Anholt and Trudy Mackay received Honorary Professorships from Beijing Forestry University, Beijing China.

Robert Anholt received the 2016 Alexander Quarles Holladay Medal for Excellence, North Carolina State University. This is the highest award at NC State University.

The Holladay Medal for Excellence recognizes members of the faculty whose careers have demonstrated outstanding achievement and sustained

impact in research, teaching or extension and engagement.

Peter Balint-Kurti received the 2016 Ruth Allen Award. This award honors individuals who have made an outstanding, innovative research contribution that has changed, or has the potential to change, the direction of research in any field of plant pathology. Peter

received the award for his sustained contributions to the field of maize disease resistance and defense response, which have provided a framework for the understanding and further investigation of this phenomenon in plants. His work in bringing the maize disease community together has resulted in a more robust scientific community able to better tackle disease problems in one of our most important crops.

Fred Gould, Trudy Mackay and Ron Sederoff were elected members of the newly established NC State University Research Leadership Academy. They also received 2016 Alumni Outstanding Research Awards.

Trudy Mackay received the 2016 Wolf Prize for Agriculture for her studies on the genetic architecture of complex traits, the discovery of principles of quantitative genetics and applications in agriculture. She was also

selected as a faculty member of Phi Kappa Phi, and received the 5th International Conference on Quantitative Genetics Award for Outstanding Contributions in Research and Teaching in Quantitative Genetics.

Fabio Morgante was inducted to The Honor Society Phi Kappa Phi.

Grants

David Aylor, Heather Patisaul and colleagues at Duke University and UNC-Chapel Hill received a $2,345,670 NIH grant to study “Systems

Toxicogenomics of Endocrine Disrupting Chemicals in Brain”

Javier Brumos received a travel grant award from the American Society of Plant Biologists to attend their annual meeting in Austin, Texas

Shante Bryant received a Provost Research Award of $10,000 from the Genetics Program for her proposal “Effect of Genetic Background and Intestinal Barrier Function in a Murine Model of Inflammatory Bowel Disease”

Genetics Major Kelly Buddin received a $5,000 Summer Research Fellowship and her mentors Freya Mowat and Michael Cowley received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Role of Hypoxia-Inducible Factors in Retinal Degenerative Disease”

David Bullock received a Provost Research Award of

$10,000 from the Genetics Program for his proposal

“Quantitative analysis of ethylene response in

Arabidopsis thaliana using infrared imaging”

Bob Franks and John Willis’ group at Duke University received a $750,000 NSF grant for their project entitled “Hybrid Seed Inviability and the Evolution of Endosperm Development in Mimulus”

Katie Hudson received a Provost Research Award of $10,000 from the Genetics Program for her proposal “Role of Sp1 in Cadmium-Induced DNA Methylation Changes”

Joel Johnstun received a housing award to attend the Association for Chemoreception Sciences (AChemS) meeting in Bonito Springs, Florida

Genetics Major Christina LaMaire received a $5,000 Summer Research Fellowship and her mentors David Aylor and Kate Meurs received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Allele Specific Gene Expression in Hybrid Mammals”

Genetics Major Emma Marx received a $5,000 Summer Research Fellowship and her mentors Freya Mowat and Matthew Breen received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine

Institute, for their project “Clinical and Genetic Characterization of an X-Linked Form of Hereditary Blindness in a North Carolina Population of Red Wolves”

Max Scott received a $500,000 grant from the AFRI Biotechnology Risk Assessment Program for the project "Development and Evaluation of Safeguards for Conditional Suppressive Gene Drives for Spotted Wing Drosophila and the New World screwworm"

Bhupinder Sehra received the American Society for Plant Biology (ASBP) Travel Grant Award to present her work at the ASPB Conference in Austin Texas

Nadia Singh received a $990,346 CAREER grant from the NSF for her work on “The Evolution of Fine-Scale Recombination Landscapes”

Genetics Major Nishi Shah received a $5,000 Summer Research Fellowship and her mentors Reade Roberts and Lisa McGraw received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Characterization of Microbiota Associated with the Reproductive Organs of the Prairie Vole”

Genetics Major Leslie Shannon received a $5,000 Summer Research Fellowship and her mentors Mary Anna Carbone, Robert Anholt and Kate Meurs received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Molecular Genetics of Glaucoma in a Canine Model”

Genetics Major Josh Slaydon received a $5,000 Summer Research Fellowship and his mentors Trudy Mackay and Mary Anna Carbone received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Cardiac Expression Patterns Associated with Feline Cardiopathy Mutations”

Genetics Major Mariah Teague received a $5,000 Summer Research Fellowship and her mentors Julie Hovarth, Seth Faith and Rob Dunn received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Skin Infection in Dogs After Routine Surgery”

Genetics Major Dana Truempy received a $5,000 Summer Research Fellowship and her mentors Johanna Elfenbein and Trudy Mackay received $4,500 research expenses from the Translational Genetics and Genomics section of the Comparative Medicine Institute, for their project “Genetics of Intestinal resistance to Salmonella Infection”

Genetics Major Anna Tsui received a prestigious Summer Undergraduate Research Fellowship from the American Society of Plant Biologists to study ethylene-auxin interactions in cotyledon epinasty under the mentorship of Anna Stepanova

Desireé Unselt received an individual NIH F31 Fellowship in the amount of $101,130 for her project “Genetic Architecture of Drosophila Lifespan”

Desireé Unselt received a Provost Research Award of $10,000 from the Genetics Program for her proposal “The Genetic Architecture of Drosophila Lifespan”

Desireé Unselt received a travel award from the Genetics Society of America to attend The Allied Genetics Conference in Orlando, Florida

Out and About

Jose Alonso gave a plenary lecture on “Translational regulation of plant hormone responses” at the 22nd International Conference on Plant Growth Substances in Toronto Ontario, Canada

Robert Anholt was an invited keynote speaker at the National Symposium: Bridging Genomics and Phenomics, Beijing, China, and visiting scholar at Beijing Forestry University, Beijing, China

Robert Anholt gave a Workshop on Oral Scientific Presentation at Beijing Forestry University, Beijing, China

Brandon Baker attended The Allied Genetics Conference of the Genetics Society of America in Orlando, Florida and presented a poster

Javier Brumos gave a talk on “How do plants make auxin?” at the Duke Plant Biology Forum, Duke University, Durham, North Carolina (with co-authors Anna Stepanova and Jose Alonso)

Javier Brumos gave a talk on “Auxin biosynthesis regulation” at the American Society of Plant Biologists (ASPB) meeting in Austin, Texas (with co-authors Anna Stepanova and Jose Alonso)

Javier Brumos gave a seminar on “New insights into auxin biosynthesis” in the Plant Molecular and Cell Biology Group Seminar Series, University of North Carolina, Chapel Hill, North Carolina (with co-authors Anna Stepanova and Jose Alonso)

Brent Chen attended The Allied Genetics Conference in Orlando, Florida and presented a poster

Logan Everett gave talks on “Deep sequencing of whole transcriptomes across the Drosophila Genetic Reference Panel’’ at the Regulatory Genomics Special Interest Group of the Intelligent Systems for Molecular Biology (ISMB) conference in Orlando, Florida; and Population, Evolutionary, and Quantitative Genetics meeting held in conjunction with The Allied Genetics Conference in Orlando, Florida

Logan Everett co-organized a workshop on “Systems Genetics in Complex Populations” and presented an overview of the Drosophila Genetic Reference Panel as a tool for dissecting complex traits at The Allied Genetics Conference in Orlando, Florida

Bob Franks was a Session Chair at the “Fruit & Seed Development” session at the 24th International Congress of the International Association of Sexual Plant Reproduction Research (IASPRR) in Tucson, AZ

Wen Huang attended the 5th International Conference on Quantitative genetics and presented a poster with co-authors Richard Lyman, Rachael Lyman, Mary Anna Carbone, Susan Harbison, Mike Magwire and Trudy Mackay.

Joel Johnstun attended the Association for Chemoreception Sciences conference in Bonito Springs, Florida

Joel Johnstun attended The Allied Genetics Conference of the Genetics Society of America in Orlando, Florida and presented a poster

Trudy Mackay attended the 5th International Conference on Quantitative Genetics and delivered an oral presentation on “Charting the genotype-phenotype map: Lessons from Drosophila”

Trudy Mackay was an invited keynote speaker at the National Symposium: Bridging Genomics and Phenomics, Beijing, China, and visiting scholar at Beijing Forestry University, Beijing, China

Trudy Mackay gave seminars at the Volcani Center, Agricultural Research Organization, Bet Dagan, Israel, and the Robert H. Smith Faculty of Agriculture; Food and Environment, Hebrew University of Jerusalem, Rehovot, Israel

Karen Merchante gave a presentation on “Hormone-mediated gene-specific translation regulation at the XIII Reunión de Biología Molecular de Plantas, Oviedo, Spain (with co-authors J Brumos, J Yun, A Stepanova and J Alonso)

Fabio Morgante presented a poster on “Effect of genetic architecture and sample size on the accuracy of genomic prediction of complex traits (with co-authors Wen Huang, Christian Maltecca and Trudy Mackay) at the 5th International Conference on Quantitative Genetics in Madison, Wisconsin

Fabio Morgante gave an oral presentation on “Effect of genetic architecture and sample size on the accuracy of genomic prediction of complex traits (with co-authors Wen Huang, Christian Maltecca and Trudy Mackay) at The Allied Genetics Conference in Orlando, Florida

Grace Parker attended The Allied Genetics Conference in Orlando, Florida and presented a poster

Max Scott was an invited speaker for the Roadmaps to Gene Drives conference in Raleigh North Carolina, where he gave a presentation on “Assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest control"

Anna Stepanova (and co-authors J Brumos, J Yun, D Bullock and J Alonso) presented a poster on “Genetic approaches to studying IPyA-independent routes of auxin biosynthesis” at the International Plant Growth Growth Substances Association Meeting, Toronto Ontario, Canada

Desireé Unselt attended The Allied Genetics Conference in Orlando, Florida and presented a poster

Sam Widmayer attended The Allied Genetics Conference in Orlando, Florida and presented a poster

Sam Widmayer attended the NIMBioS Tutorial in Evolutionary Quantitative Genetics in Knoxville, Tennessee

Aki Yamamoto attended The Allied Genetics Conference in Orlando, Florida and gave a platform presentation

Jeff Yoder was an invited keynote speaker at the International Conference of Fish & Shellfish Immunology in Portland, Maine

Jeff Yoder was an invited speaker and presented a poster at the North American Comparative Immunology Workshop in Charlottetown, Prince Edward Island, Canada

Zhao Bang Zeng attended the 5th International Conference on Quantitative Genetics and delivered an oral presentation in the Epistasis and G x E interaction session

Of Note…

The Alonso-Stepanova lab gave five two-hour Plants4Kids hands-on outreach demos at the NC Museum of Natural Sciences, Science Saturday as well as two full-day demos on Darwin Day and Triangle SciTech Expo

The Alonso-Stepanova and Franks groups held a collaborative NCSU- University of Adelaide workshop with Dr. Matt Tucker (UA, Australia)

Robert Anholt is a member of the Association for Chemoreception Sciences Annual Meeting Strategic Planning Committee

Bob Franks was recently appointed as an Associate Editor for Frontiers in Plant Sciences, Plant Evolution and Development Section.

Sneha Mokashi attended the Neurobiology of Drosophila course at Cold Spring Harbor

Bhupinder Sehra attended the EMBO Practical Course in vivo Plant Imaging at EMBL in Heidelberg, Germany

Phenotypic Effects of Mutations Depend on Genetic Background

By Megan Williamson

On February 15, 2016, the Genetics Program was proud to host Dr. Ian Dworkin, Associate Professor in the Department of Biology at McMaster University in Hamilton, Ontario, Canada, as the featured Alumnus Speaker of the semester. Dr. Dworkin performed his postdoctoral research in the laboratory of Dr. Gregory Gibson, now at the Georgia Institute of Technology. His current research focuses on understanding the evolution of complex phenotypes primarily using the model system Drosophila melanogaster. His talk was entitled “Genetic Background and its Impacts on the Analysis of Mutations, Genes, and Evolutionary Trajectories.”

In nature, the phenomenon that mutations in different genetic backgrounds have different phenotypic effects is widespread. However, the mechanism underlying this phenomenon is still a mystery. Developing and applying integrative approaches to address this question is the main focus of Dr. Dworkin’s lab. Specifically, he uses both genetic analyses and analyses of genome wide gene expression to assess the effects of the same mutations in different genetic backgrounds. His model system is wing shape in D. melanogaster, because many different component phenotypes affect shape and shape is easy to quantify in the two-dimensional wing. Mutations of the scalloped gene, which along with vestigial is required for proper wing development, have smaller, deformed wings with less tissue. Dr. Dworkin presented results showing that the effects of the scalloped alleles on wing shape vary dramatically when introgressed into different wild type genetic backgrounds. Therefore, epistatic modifiers of scalloped segregate in natural populations.

Dr. Dworkin then described further experiments to identify these modifier loci, including quantitative trait locus mapping and genome wide gene expression differences using RNA sequencing. These studies led him to conclude that higher order epistatic interactions are responsible for modifying the scalloped phenotypes. Dr. Dworkin’s research highlights the importance of background dependence of mutational effects in D. melanogaster and approaches that can be used to dissect the genetic basis of these interactions. It is likely this phenomenon is important in other species.

Human Physiological Adaptation By

Jennifer Baltzegar

On March 14, 2016 the Genetics Graduate Students hosted Dr. Rasmus Nielsen as a Distinguished Speaker in the weekly genetics seminar series. Dr. Nielsen is a Professor in the Department of Integrative Biology at the University of California, Berkeley. The

excellent talk he delivered was titled, “The Genomics of Human Physiological Adaptation.”

Dr. Nielsen began his talk by describing various types of human adaptations to different environments. His goal is to determine if there is a genetic basis for human adaptation to different environments, and if there is, he wants to pinpoint what the difference is. Another overarching goal that has motivated much of his work is finding evidence of natural selection in DNA sequences. Several of his recent projects have attempted to do just that.

Tibetan people are a distinct ethnic group of people who live at high elevation in the Tibet Autonomous Region of China. One of the major physiological challenges associated with living at high elevation is hypoxia. When humans experience hypoxia the number of red blood cells increase and over a long period of time this can lead to detrimental side effects such as heart disease and preeclampsia. Tibetans living at altitudes above 4000 meters do not experience the negative long term side effects of hypoxia. In contrast, Han people – a distinct ethnic group from mainland China – do experience these

side effects even though they are genetically similar (FST = 0.026) (Yi et al. 2010), however, the haplotypes between the Tibetans and the Hans are more different than would be predicted mathematically and this has been attributed to the introgression of Denisovan DNA into the genomes of the Tibetans. Nielsen called this specific example of introgression “adaptive introgression” because presumably, the portions of the Denisovan genome that have been retained in the Tibetan genome contribute to their physiological adaptation to living at high elevations. Altitude adaptation has also been found in Ethiopian populations, but those populations do not show signs of Denisovan introgression. Rather, in the Ethiopian populations the adaptations are attributed to other genetic mutations.

Dr. Nielsen also spoke about some of his work on the evolution and physiological adaptations to diet in Greenlandic Inuit populations. Historically, Inuit people have subsisted on high fat low fiber diets, largely based on marine mammals. This type of diet is conventionally thought of as unhealthy, but when the Inuit people eat this diet they experienced very little overweight and cardiovascular disease or other ailments typically thought to be associated with a high fat low fiber diet. Furthermore, when non-Inuit people follow the Inuit diet they do not receive the benefits that the Inuit people do. In recent decades many Inuit groups have transitioned from eating a traditional diet to a more modern Western Diet and have begun to develop a very high rate of Type II Diabetes. This phenomenon has been associated with specific genetic differences in the Inuit genomes compared to other populations of people.

Dr. Nielsen’s very engaging talk gave further insight into differences of our own species as well as, once again, emphasizing the importance that genetic background plays in the presentation of phenotypes.

Reference Cited:

Yi, X, Y Liang, E Huerta-Sanchez, X Jin, Z X P Cuo, J E Pool, X Xu, et al. 2010. “Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude.” Science 329 : 75–78.

Shaking Up the System By

Katherine Knudsen Myers

On Monday, April 4th, Dr. Brian Oliver, Section Chief of the Section of Developmental Genomics at the National Institute of Diabetes and Digestive and Kidney Diseases, visited us as a Genetics Graduate Student invited

speaker. Dr. Oliver is well known in the Drosophila genetics field for his work in sex determination. His lab currently focuses on understanding the role of gene networks in disease susceptibility with the goal of improving predictive models of gene and pathway function. His talk, “Perturbing Gene Networks and Expression in Drosophila,” showed that Dr. Oliver is fond of using analogies to convey complex scientific information.

In the beginning of his talk, Dr. Oliver described the past century of the rapidly expanding field of genetics, including discussion of the large number of genomes sequenced and the understanding of the functions of countless genes. However, even with the development of such a vast amount of knowledge, there is still uncertainty in how the relationship between genotype and phenotype results in individuals with specific characteristics. Dr. Oliver explained how molecular genetics can be described like a clock, with the genome as the instructions and the parts for building an intricate, functional system. Each clock part, like each gene, can be defined as necessary and/or sufficient for the different functions of the system. These parts are deterministic and can be tested experimentally. However, for population genetics, a genome can be viewed less like a clock and more like a cloud or weather forecasting model. Like different types of clouds, a genome can be categorized, described, and simulated. These simulations allow for predictions of large and small effects that may not be easily addressed experimentally.

Dr. Oliver’s research focuses on the potential use of gene networks in model organisms as predictive models for disease susceptibility in humans. In order

to characterize and understand the function of these networks, they need to be perturbed. Dr. Oliver discussed how secondary changes in gene expression are not random, and the most relevant changes are only seen once a network has been disrupted. These changes can then be compared to the normal functioning system. Using another analogy, Dr. Oliver described how air travel was disrupted for six days in airports as far away as Heathrow after the Icelandic volcano, Eyjafjallajökull, erupted. This perturbation identified parts of the air travel system that stopped working, highlighting how those parts functioned in the normal system as a whole. Gene networks, like the air travel system, may have easily identifiable large effects with smaller effects remaining hidden.

To close out his talk, Dr. Oliver reminded the audience that we have only begun to scratch the large effect surface, and that “perturbations result in conceptually simply, but devilishly complicated reactions from the genome.” If these reactions can be characterized and understood, we may creep closer to understanding the relationship between genotype and phenotype.

Molecular Investigation of Complex Disorders

By Erin Peterson

On Monday, April 25th, the Genetics Graduate students hosted Dr. Aravinda Chakravarti, Professor of Medicine, Pediatrics, Molecular Biology & Genetics, and Biostatistics from John Hopkins School of Medicine. Dr. Chakravarti spoke about the importance of developing models for genetics in his talk titled,

“The Molecular Basis for Complex Disease.” Utilizing the clinical connections and much collaboration, Dr. Chakravarti works on human diseases to develop genetic networks. He also utilizes model organisms, including mice and zebrafish, to aid in the understanding of the genetic mechanisms underpinning these diseases.

He began his talk by stressing the importance of using both statistical and molecular models in

understanding diseases and the historical use of mapping to determine their molecular basis. Fisher’s Model was used as an example for how we are able to characterize and quantify phenotypes extremely well but are still unable to elucidate the molecular basis of disorders with high fidelity. This led to a discussion of how we can understand the genetics of a trait through its impact on gene regulatory networks. He went on to speak about how we are able to quantify the outputs of genes, leading to better understanding of how they interact and how this allows us to then study major processes to which multiple genes and regulatory mechanisms contribute. Dr. Chakravarti broke down how gene regulatory networks function at different levels and how thinking of diseases in this manner can be used to elucidate their molecular causes.

To explain this process, Dr. Chakravarti focused on Hirschsprung Disease, a disorder that has many syndromic associations, including Down Syndrome. Hirschsprung is characterized by missing nerve cells in the muscles of the large intestine. This disease is known to disrupt cellular interaction between the neuroblasts and the mesenchyme, and also affects proliferation, differentiation, migration, and innervation of cells. Since humans are relatively outbred, we can perform sequencing to determine causative or associated genes with relative ease. He then described functional validation analyses of the associated genes using the zebrafish model. These studies confirmed the candidate gene RET. The RET regulatory region was sequenced in affected and control people, leading to the identification of polymorphisms that accounted for a 30-fold difference in risk. Finally, Dr. Chakravarti explained the importance of evaluating the many different molecular mechanisms through which genetic variants can exert their effects, including changes in histone marks, enhancer activity, or gene expression. These studies elucidate gene networks implicated in the molecular underpinning of complex disease.

The Allied Genetics Conference (aka The Totally Awesome Genetics

Conference) Orlando, Florida

A large contingent of Genetics program members attended the TAGC in Orlando this summer. Here

are some of the highlights of the conference from their perspectives.

Brandon Baker reports that attending TAGC was a life-changing experience. The conference contained a great amount of truly fascinating presentations each and every day. One presentation that truly fascinated him was about sleep, specifically when, why and how sleep occurs. Using Drosophila melanogaster as a model system, Dr. Amita Sehgal from the University of Pennsylvania described the daily timing of sleep, function of sleep and regulation of sleep onset. Sleep interests Brandon because his work uses psychostimulant drugs that cause a reduction in sleep in many organisms including Drosophila melanogaster. Daily timing of sleep is regulated by many different neurons in the brain known as clock cells that relay information to the rest of the brain via pigment dispersing factor. Sleep functions in a number of different ways including enhancing plasticity in the developing visual cortex. Young flies sleep more and fall asleep faster than older flies. On top of that, brain dopamine is lower in young flies. Since Brandon works with psychostimulants that act on the dopamine in the brain, this work led him to question whether drug consumption may differ as flies age. The Sehgal group also observed a reduction in both courtship and copulation when fliesa re sleep-deprived. This has also been observed in flies that are under the influence of many different drugs. The Sehgal group has identified many genes that regulate sleep onset, including a gene that encodes an acetylcholine receptor and a gene that encodes a voltage gated potassium channel. Sleep is an essential part of our lives taking up close to 30% of our time yet it is a topic still has so much information yet to be discovered. This was just one of many tremendous presentations given at TAGC. The experience was truly amazing and presented an opportunity for the genetics community to come together and share great research.

Brent Chen was interested in the presentation of Dr. Teresa Lee, a post-doctoral fellow in the David Katz lab at Emory University, on her research detailing a potential explanation to the transgenerational epigenetic inheritance of longevity phenomena in C. elegans described by Greer et al in 2011. As a core component in the histone H3 lysine 4 trimethylation (H3K4me3) complex, WDR-5 regulates lifespan

and wdr-5 null mutants are long-lived. After 2 generations of mating the wdr-5 mutants to wild type worms, Greer produced long-lived worms genetically identical to wild type and that surprisingly still could pass the extended lifespan phenotype to the next generation. This extended life phenotype in the wild type background lasted for four generations before finally returning to normal lifespan, suggesting there was epigenetic memory of the wdr-5 mutant ancestry in the wild type worms. At Emory, Lee observed a loss of H3K4me3 in wdr-5 mutants, as well as a dramatic increase in H3K9me2 using ChIP-PCR. This allowed her to ask whether H3K9me2 confers longevity and allow for its inheritance. Lee found wdr-5 loss required 18 generations before the extension of lifespan was maximized. In fact, the first generation with the wdr-5 mutation actually had a shorter average lifespan compared to wild type. Longevity was found to gradually increase in subsequent generations and correlated with the gradual accumulation of H3K9me2 levels. She suggests that having low levels of H3K9me2 and no H3K4me3 hurts the P0 generation. As each generation increases the H3K9me2 load, longevity increases over time. To test the hypothesis that accumulation of H3K9me2 is required for increased longevity in the wdr-5 mutante, she mutated met-2, a methyltransferase necessary for the methylation of H3K9, in wdr-5 mutants. Lee found that loss of met-2 abolishes the increase longevity phenotype in wdr-5 mutants and also prevents the inheritance of longevity when crossed with wild type. Her data suggest that the inheritance of the repressive chromatin H3K9me2 enables inheritance of longevity. Additionally, the failure to reset chromatin between generations affects complex traits such as lifespan.

Logan Everett was intrigued by a presentation by David Rand (Brown University on “GxG and GxE: Not So Different After All?”. Two potential sources of missing heritability are epistasis (genotype by genotype or “GxG” interactions) and genotype by environment (GxE) interactions, both of which produce non-additive effects. David Rand presented an intriguing argument that perhaps these two aspects of genetic architecture are not as distinct as they might seem. The Rand lab is using a subset of the Drosophila Genetic Reference Panel (DGRP)

sequenced, inbred lines to study the interactions of nuclear and mitochondrial genotypes and environmental factors that influence mitochondrial metabolism, such as diet and oxygen levels. These experiments have demonstrated that some GxG interactions can also be thought of as interactions between a single locus and the “cellular environment”. In other words, some alleles perturb conditions within the cell, such as levels of metabolites or reactive oxygen species, and the indirect effects of these changes interact with other genotypes. Similar changes to the cellular environment can also be recapitulated by changes in diet or exposure to hypoxic conditions, thus revealing an important overlap in the GxG and GxE partitions of genetic architecture. An important hypothesis stemming from this work is the suggestion that loci which perturb the cellular environment should be detectable as hubs in epistasis networks.

Joel Johnstun thought that one of the most memorable talks he attended was by Lawrence Reiter, who used the DGRP to identify SNPs associated with autism-like phenotypes. In brief, they did three separate GWA studies using phenotypes that are central to autism spectrum disorder (in flies this amounted to assaying mating behavior, social space, and grooming), and found that variants in the sulfateless (sfl) gene came up significant in all three. The sfl gene encodes an enzyme which is essential for the synthesis of heparan sulfate glycosaminoglycans, and may be important for cell-cell interactions during neural development. He also gained a bit of insight from another talk, this time by Isaac Cervantes-Sandoval, about the gene scribble and its effect on active forgetting in Drosophila. In the context of his project he brought up the line of reasoning that if two genes are involved in the same pathway, then there should be no additive effect on the phenotype between the two RNAi knockdowns. This is reminiscent of using complementation groups to determine the number of genes in a given pathway. The reason this impressed Joel is because he thought that this same reasoning may also be applied to his project: if the separate knockout of two paralogs is found to have an effect on a given phenotype, but the knockout of them both does not have an additive effect on that phenotype, then that may indicate that the paralogs are not only functionally redundant on

the behavioral level, but also on a mechanistic level. Another highlight came from the poster session, in which I noticed that two posters from different labs had phenotyped flies kept on a high sugar and low sugar diet, and found – apparently contrary to the literature – that the flies kept on a high sugar diet lived longer. Both presenters (one of whom had used 30 DGRP lines to do a mini GWAS) indicated that they were going to redo their assays because they could not readily interpret their results.

Fabio Morgante reports that TAGC was a great success. He found the Population, Evolutionary and Quantitative Genetics (PEQG) meeting most stimulating. This meeting brought together research on model and non-model organisms spanning from lab or field experiments to novel statistical models to tackle old questions. What appeared to be a common theme of this particular meeting was how a system genetics approach has become the gold standard to answer basic questions in biology with model organisms. What was most surprising, though, was how this approach is becoming popular also among breeding species. DJ de Koning (SLU, Sweden) showed how combining QTL mapping, GWAS and RNA sequencing can be used to improve bone strength in laying hens, an important commercial trait. This is a great example of how some basic research approaches can be used successfully in applied research.

Grace Parker liked the presentation of Philipp Messer from Cornell entitled “Dynamics and feasibility of CRISPR/Cas9-mediated gene drives in natural populations.” His lab’s goal was to decide, aside from ethical considerations, if a CRISPR/Cas9 system will prevail in a natural population long-term. Their main concern is that resistance alleles may evolve in the natural population and prevent the gRNA from binding to the target sequence. These alleles may occur from random mutation, non-homologous end joining (NHEJ), or standing genetic variation. Their model defined the probability that resistance alleles will pervade as a function of the mutation rate and the NHEJ rate. While mutation rate has an effect, it is essential the NHEJ rate be low for the resistance alleles not to pervade. Proposed possibilities to lower the probability of resistance alleles pervading are using a driver with a low fitness cost or using an essential gene that is unlikely to

develop resistance alleles. In conclusion, the CRISPR/Cas9-mediated gene drive has a high probability of reaching high frequencies in a natural population, but it will be outcompeted long-term by resistance alleles.

Desireé Unselt found the presentation of Ian Kutch from the University of Central Florida on “Does the Y-chromosome facilitate sexual dimorphic evolution or constrain autosomal evolution?” very interesting. To better understand the sex-specific variation in gene expression involved in the adaptive evolution of sexually dimorphic traits, Ian Kutch and his lab examined Y-linked regulatory variation (YRV), which has previously been associated in the influence of several autosomal and X-linked genes in multiple species. For YRV to facilitate sexually dimorphic evolution, YRV must exist within natural populations and influence fitness. A phenotype of interest is immunity. Immune gene regulation differs in Drosophila melanogaster males and females as well as appears to be influenced by the Y-chromosome, hinting at contribution to dimorphic immune evolution. Ian and his lab used D. melanogaster derived from Orlando, FL to explore how selection could shape YRV. To determine if YRV exists within a population, they introgressed 30 wild-derived Y-chromosomes into the same genetic background (Y-lines). Following introgression, the flies were assayed for variation in immune gene expression. Then, the same Y-chromosome lines were tested for differential responses to a bacterial pathogen to determine if YRV has any fitness consequences. Finally, 4 Y-chromosomes were crossed into 4 different genetic backgrounds to determine if intra-population YRV involved additive genetic variation. Ian found that the Y-line males differed in their immune gene regulation and their ability to defend against a pathogen. Gene expression and bacterial defense were positively genetically correlated. Their results suggest that intra-population YRV exists and that the variation is associated with survival to a pathogen. The effect of YRV was approximately 42.6% of the genetic variation in their experimental lines. However, the majority of this variation was due to non-additive genetic variation, indicating that selection may not act on immune-related YRV and may constrain adaptive evolution of insect immune function.

Aki Yamamoto found the Joint Plenary sessions impressive. He especially liked the presentation of Molly Przeworski (Columbia University), who demonstrated recombination hot spot evolution using mice and bird species and left him wondering why recombination mechanisms are so variable among lineages. He was also fascinated by the talk of Amita Sehgal (University of Pennsylvania) on Drosophila sleep. He ended up concluding that we still don’t know why we sleep and why sleep depletion kills organisms.

Publications

The following publications of members of the Program in Genetics have appeared in print. Names in bold font are current members of the Program in Genetics

Anstead CA, Batterham P, Korhonen PK, Young ND, Hall RS, Bowles VM, Richards S, Scott MJ, Gasser RB. 2016. A blow to the fly - Lucilia cuprina draft genome and transcriptome to support advances in biology and biotechnology. Biotechnol Adv 34: 605-620.

Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: A screening approach using ToxCast™ high-throughput data. Environ Health Perspect 124: 1141-1154.

Bartholomé J, Van Heerwaarden J, Isik F, Boury C, Vidal M, Plomion C, Bouffier L. 2016. Performance of genomic prediction within and across generations in maritime pine. BMC Genomics 17: 604.

Benoit JB, Adelman ZN, Reinhardt K, Dolan A, Poelchau M, Jennings EC, Szuter EM, Hagan RW, Gujar H, Shukla JN, Zhu F, Mohan M, Nelson DR, Rosendale AJ, Derst C, Resnik V, Wernig S, Menegazzi P, Wegener C, Peschel N, Hendershot JM, Blenau W, Predel R, Johnston PR, Ioannidis P, Waterhouse RM, Nauen R, Schorn C, Ott MC, Maiwald F, Johnston JS, Gondhalekar AD, Scharf ME, Peterson BF, Raje KR, Hottel BA, Armisén D, Crumière AJ, Refki PN, Santos ME, Sghaier E, Viala S, Khila A, Ahn SJ, Childers C, Lee CY, Lin H, Hughes DS, Duncan EJ, Murali SC, Qu J, Dugan S,

Lee SL, Chao H, Dinh H, Han Y, Doddapaneni H, Worley KC, Muzny DM, Wheeler D, Panfilio KA, Vargas Jentzsch IM, Vargo EL, Booth W, Friedrich M, Weirauch MT, Anderson MA, Jones JW, Mittapalli O, Zhao C, Zhou JJ, Evans JD, Attardo GM, Robertson HM, Zdobnov EM, Ribeiro JM, Gibbs RA, Werren JH, Palli SR, Schal C, Richards S. 2016. Unique features of a global human ectoparasite identified through sequencing of the bed bug genome. Nat Commun 7: 10165.

Borgeat K, Stern J, Meurs KM, Fuentes VL, Connolly DJ. 2015. The influence of clinical and genetic factors on left ventricular wall thickness in Ragdoll cats. J Vet Cardiol 17 Suppl 1: S258-S267.

Braasch I, Gehrke AR, Smith JJ, Kawasaki K, Manousaki T, Pasquier J, Amores A, Desvignes T, Batzel P, Catchen J, Berlin AM, Campbell MS, Barrell D, Martin KJ, Mulley JF, Ravi V, Lee AP, Nakamura T, Chalopin D, Fan S, Wcisel D, Cañestro C, Sydes J, Beaudry FEG, Sun Y, Hertel J, Beam MJ, Di Palma F, Fasold M, Ishiyama M, Johnson J, Kehr S, Lara M, Letaw JH, Litman GW, Litman RT, Mikami M, Ota T, Saha NR, Williams L, Stadler PF, Wang H, Taylor JS, Fontenot Q, Ferrara A, Searle SMJ, Aken B, Yandell M, Schneider I, Yoder JA, Volff J-N, Meyer A, Amemiya CT, Venkatesh B, Holland PWH, Guiguen Y, Bobe J, Shubin NH, Alföldi J, Lindblad-Toh K, Postlethwait JH. 2016. The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons. Nat Genet 48: 427-437.

Castel A, Olby NJ. 2016. Acute change in neurological level following canine intervertebral disc herniation. J Small Anim Pract 57: 220.

Čepl J, Holá D, Stejskal J, Korecký J, Kočová M, Lhotáková Z, Tomášková I, Palovská M, Rothová O,

Whetten RW, Kaňák J, Albrechtová J, Lstibůrek M. 2016. Genetic variability and heritability of chlorophyll a fluorescence parameters in Scots pine (Pinus sylvestris L.). Tree Physiol 36: 883-895.

Cerda-Gonzalez S, Olby NJ, Griffith EH. 2016. Longitudinal study of the relationship among craniocervical Mmorphology, clinical progression, and syringomyelia in a cohort of Cavalier King Charles Spaniels. J Vet Intern Med 30: 1090-1098.

Choi DB, Grieco JP, Apperson CS, Schal C, Ponnusamy L, Wesson DM, Achee NL. 2016. Effect of spatial repellent exposure on dengue vector attraction to oviposition sites. PLoS Negl Trop Dis 10: e0004850.

Dalal J, Lewis DR, Tietz O, Brown EM, Brown CS, Palme K, Muday GK, Sederoff HW. 2016. ROSY1, a novel regulator of gravitropic response is a stigmasterol binding protein. J Plant Physiol 196-197: 28-40.

Dembeck LM, Böröczky K, Huang W, Schal C, Anholt RRH, Mackay TFC. 2015. Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster. Elife 4: e09861.

Edwards SM, Sørensen IF, Sarup P, Mackay TFC, Sørensen P. 2016. Genomic prediction for quantitative traits is improved by mapping variants to gene ontology categories in Drosophila melanogaster. Genetics 203: 1871-1883.

Friedenberg SG, Buhrman G, Chdid L, Olby NJ, Olivry T, Guillaumin J, O'Toole T, Goggs R, Kennedy LJ, Rose RB, Meurs KM. 2016. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs. Immunogenetics 68: 205-217.

Friedenberg SG, Chdid L, Keene B, Sherry B, Motsinger-Reif A, Meurs KM. 2016. Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy. Am J Vet Res 77: 693-699.

Friedenberg SG, Meurs KM. 2016. Genotype imputation in the domestic dog. Mamm Genome 27: 485-494.

Fritz ML, Paa S, Baltzegar J, Gould F. 2016. Application of a dense genetic map for assessment of genomic responses to selection and inbreeding in Heliothis virescens. Insect Molecular Biology 25: 385-400.

Gerken AR, Mackay TFC, Morgan TJ. 2016. Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection. J Therm Biol 59: 77-85.

Gong X, Flores-Vergara MA, Hong JH, Chu H, Lim J, Franks RG, Liu Z, Xu J. 2016. SEUSS integrates gibberellin signaling with transcriptional inputs from the SHR-SCR-SCL3 module to regulate middle cortex formation in the Arabidopsis root. Plant Physiol 170: 1675-1683.

Gorney AM, Blau SR, Dohse CS, Griffith EH, Williams KD, Lim JH, Knazovicky D, Lascelles BD, Olby NJ. 2016. Mechanical and thermal sensory testing in normal chondrodystrophoid dogs and dogs with spinal cord injury caused by thoracolumbar intervertebral disc herniations. J Vet Intern Med 30: 627-635.

Gutierrez NA, Serão NV, Patience JF. 2016. Effects of distillers' dried grains with solubles and soybean oil on dietary lipid, fiber, and amino acid digestibility in corn-based diets fed to growing pigs. J Anim Sci 94: 1508-1519.

He X, Zhou S, St. Armour GE, Mackay TFC, Anholt RRH. 2016. Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior. Genes Brain Behav 15: 280-290.

Horn BW, Gell RM, Singh R, Sorensen RB, Carbone I. 2016. Sexual reproduction in Aspergillus flavus Sclerotia: Acquisition of novel alleles from soil populations and uniparental mitochondrial inheritance. PLoS One 11: e0146169.

Hu YJ, Sun W, Tzeng JY, Perou CM. 2016. Proper use of allele-specific expression improves statistical power for cis-eQTL mapping with RNA-seq data. J Am Stat Assoc 110: 962-974.

Hu Q, Merchante C, Stepanova AN, Alonso JM, Heber S. 2016. Genome-wide search for translated upstream open reading frames in Arabidopsis thaliana. IEEE Trans NanoBioscience 15: 148-57.

Huang W, Lyman RF, Lyman RA, Carbone MA, Harbison ST, Magwire MM, Mackay TFC. 2016. Spontaneous mutations and the origin and maintenance of quantitative genetic variation. Elife 5: e14625.

Hunter CM, Huang W, Mackay TFC, Singh ND. 2016. The genetic architecture of natural variation in recombination rate in Drosophila melanogaster. PLoS Genet 12: e1005951.

Hunter CM, Robinson MC, Aylor DL, Singh ND. 2016. Genetic background, maternal age, and interaction effects mediate rates of crossing over in Drosophila melanogaster females. G3 6: 1409-1416.

Isik F, Bartholomé J, Farjat A, Chancerel E, Raffin A, Sanchez L, Plomion C, Bouffier L. 2016. Genomic selection in maritime pine. Plant Sci 242: 108-119.

Jeng XJ, Daye ZJ, Lu W, Tzeng JY. 2016. Rare variants association analysis in large-scale sequencing studies at the single locus level. PLoS Comput Biol 12: e1004993.

Jensen K, Ko AE, Schal C, Silverman J. 2016. Insecticide resistance and nutrition interactively shape life-history parameters in German cockroaches. Sci Rep 6: 28731.

Jermusyk AA, Murphy NP, Reeves GT. 2016. Analyzing negative feedback using a synthetic gene network expressed in the Drosophila melanogaster embryo. BMC Syst Biol 10: 85.

Ji X, Griffing A, Thorne JL. 2016. A phylogenetic approach finds abundant interlocus gene conversion in yeast. Mol Biol Evol 33: 2469-2476.

Jiao S, Tiezzi F, Huang Y, Gray KA, Maltecca C. 2016. The use of multiple imputation for the accurate measurements of individual feed intake by electronic feeders. J Anim Sci 94: 824-832.

Judson R, Houck K, Martin M, Richard AM, Knudsen TB, Shah I, Little S, Wambaugh J, Woodrow Setzer R, Kothya P, Phuong J, Filer D, Smith D, Reif D, Rotroff D, Kleinstreuer N, Sipes N, Xia M, Huang R, Crofton K, Thomas RS. 2016. Analysis of the effects of cell stress and cytotoxicity on in vitro assay activity across a diverse chemical and assay space. Toxicol Sci 152: 323-339.

Kittleson MD, Meurs KM, Harris SP. 2015. The genetic basis of hypertrophic cardiomyopathy in cats and humans. J Vet Cardiol 17 Suppl 1: S53-S73.

Ko AE, Bieman DN, Schal C, Silverman J. 2016. Insecticide resistance and diminished secondary kill performance of bait formulations against German cockroaches (Dictyoptera: Blattellidae). Pest Manag Sci 72: 1778-1784.

Ko AE, Schal C, Silverman J. 2016. Diet quality affects bait performance in German cockroaches

(Dictyoptera: Blattellidae). Pest Manag Sci 72: 1826-1836.

Kong D, Maity A, Hsu FC, Tzeng JY. 2016. Testing and estimation in marker-set association study using semiparametric quantile regression kernel machine. Biometrics 72: 364-371.

Kuzu G, Kaye EG, Chery J, Siggers T, Yang L, Dobson JR, Boor S, Bliss J, Liu W, Jogl G, Rohs R, Singh ND, Bulyk ML, Tolstorukov MY, Larschan E. Expansion of GA dinucleotide repeats increases the density of CLAMP binding sites on the X-chromosome to promote Drosophila dosage compensation. PLoS Genet 12: e1006120.

Lange C, Mowat F, Sayed H, Mehad M, Duluc L, Piper S, Luhmann U, Nandi M, Kelly P, Smith A, Ali R, Leiper J, Bainbridge J. 2016. Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis. Exp Eye Res 147: 148-155.

LeBlanc AK, Breen M, Choyke P, Dewhirst M, Fan TM, Gustafson DL, Helman LJ, Kastan MB, Knapp DW, Levin WJ, London C, Mason N, Mazcko C, Olson PN, Page R, Teicher BA, Thamm DH, Trent JM, Vail DM, Khanna C. 2016. Perspectives from man's best friend: National Academy of Medicine's Workshop on Comparative Oncology. Sci Transl Med 8: 324ps5.

LeBlanc AK, Mazcko C, Brown DE, Koehler JW, Miller AD, Miller CR, Bentley RT, Packer RA, Breen M, Boudreau CE, Levine JM, Simpson RM, Halsey C, Kisseberth W, Rossmeisl JH Jr, Dickinson PJ, Fan TM, Corps K, Aldape K, Puduvalli V, Pluhar GE, Gilbert MR. 2016. Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients. Neuro Oncol 18: 1209-1218.

Lee HJ, Kishino H, Rodrigue N, Thorne JL. 2016. Grouping substitution types into different relaxed molecular clocks. Philos Trans R Soc Lond B Biol Sci. 371: 20150141.

Li F, Scott MJ. 2016. CRISPR/Cas9-mediated mutagenesis of the white and Sex lethal loci in the invasive pest, Drosophila suzukii. Biochem Biophys Res Commun 469: 911-916.

Linger RJ, Belikoff EJ, Yan Y, Li F, Wantuch HA, Fitzsimons HL, Scott MJ. 2016 Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor. BMC Biotechnol 16: 30.

Liu X, Zhang J, Abuahmad A, Franks RG, Xie DY, Xiang QY. 2016. Analysis of two TFL1 homologs of dogwood species (Cornus L.) indicates functional conservation in control of transition to flowering. Planta 243: 1129-1141.

Matos YK, Schal C. 2016. Laboratory and field evaluation of Zyrox fly granular bait against Asian and German cockroaches (Dictyoptera: Blattellidae). J Econ Entomol 109: 1807-1812.

Meurs KM, Weidman JA, Rosenthal SL, Lahmers KK, Friedenberg SG. 2016. Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns. J Am Vet Med Assoc 248: 1135-1138.

Moore FE, Garcia EG, Lobbardi R, Jain E, Tang Q, Moore JC, Cortes M, Molodtsov A, Kasheta M, Luo CC, Garcia AJ, Mylvaganam R, Yoder JA, Blackburn JS, Sadreyev RI, Ceol CJ, North TE, Langenau DM. 2016. Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish. J Exp Med 213: 979-992.

Okamoto KW, Gould F, Lloyd AL. 2016. Integrating transgenic vector manipulation with clinical interventions to manage vector-borne diseases. PLoS Comput Biol 12: e1004695.

Olby NJ, Muguet-Chanoit AC, Lim JH, Davidian M, Mariani CL, Freeman AC, Platt SR, Humphrey J, Kent M, Giovanella C, Longshore R, Early PJ, Muñana KR. 2016. A placebo-controlled, prospective, randomized clinical trial of polyethylene glycol and methylprednisolone sodium succinate in dogs with intervertebral disk herniation. J Vet Intern Med 30: 206-214.

Olukolu BA, Tracy WF, Wisser R, De Vries B, Balint-Kurti PJ. 2016. A genome-wide association study for partial resistance to maize common rust. Phytopathology 106: 745-751.

Oneal E, Willis JH, Franks RG. 2016. Disruption of endosperm development is a major cause of hybrid

seed inviability between Mimulus guttatus and Mimulus nudatus. New Phytol 210: 1107-1120.

Parker Gaddis KL, Cole JB, Clay JS, Maltecca C. 2016. Benchmarking dairy herd health status using routinely recorded herd summary data. J Dairy Sci 99: 1298-1314.

Paz-Soldan VA, Yukich J, Soonthorndhada A, Giron M, Apperson CS, Ponnusamy L, Schal C, Morrison AC, Keating J, Wesson DM. 2016. Design and testing of novel lethal ovitrap to reduce populations of Aedes mosquitoes: Community-based participatory research between industry, academia and communities in Peru and Thailand. PLoS One 11: e0160386.

Plomion C, Bartholomé J, Lesur I, Boury C, Rodríguez-Quilón I, Lagraulet H, Ehrenmann F, Bouffier L, Gion JM, Grivet D, de Miguel M, de María N, Cervera MT, Bagnoli F, Isik F, Vendramin GG, González-Martínez SC. 2016. High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster). Mol Ecol Resour 16: 574-587.

Provart NJ, Alonso J, Assmann SM, Bergmann D, Brady SM, Brkljacic J, Browse J, Chapple C, Colot V, Cutler S, Dangl J, Ehrhardt D, Friesner JD, Frommer WB, Grotewold E, Meyerowitz E, Nemhauser J, Nordborg M, Pikaard C, Shanklin J, Somerville C, Stitt M, Torii KU, Waese J, Wagner D, McCourt P. 2016. 50 years of Arabidopsis research: highlights and future directions. New Phytol 209: 921-944

Putz AM, Tiezzi F, Maltecca C, Gray KA, Knauer MT. 2015. Variance component estimates for alternative litter size traits in swine. J Anim Sci 93: 5153-5163.

Raab RW, Moore JE, Vargo EL, Rose L, Raab J, Culbreth M, Burzumato G, Koyee A, McCarthy B, Raffaele J, Schal C, Vaidyanathan R. 2016. New introductions, spread of existing matrilines, and high rates of pyrethroid resistance result in chronic infestations of bed bugs (Cimex lectularius L.) in lower-income housing. PLoS One 11: e0117805.

Rangel J, Böröczky K, Schal C, Tarpy DR. 2016. Honey bee (Apis mellifera) queen reproductive potential affects queen mandibular gland pheromone composition and worker retinue response. PLoS One 11: e0156027.

Rebuli ME, Camacho L, Adonay ME, Reif DM, Aylor DL, Patisaul HB. 2015. Impact of low-dose oral exposure to bisphenol A (BPA) on juvenile and adult rat exploratory and anxiety behavior: A CLARITY-BPA Consortium study. Toxicol Sci 148: 341-354.

Reif DM, Truong L, Mandrell D, Marvel S, Zhang G, Tanguay RL. 2016. High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes. Arch Toxicol 90: 1459-1470.

Riedl CA, Oster S, Busto M, Mackay TFC, Sokolowski MB. 2016. Natural variability in Drosophila larval and pupal NaCl tolerance. J Insect Physiol 88: 15-23.

Riesch R, Tobler M, Lerp H, Jourdan J, Doumas T, Nosil P, Langerhans RB, Plath M. 2016. Extremophile Poeciliidae: multivariate insights into the complexity of speciation along replicated ecological gradients. BMC Evol Biol 16: 136.

Rodriguez-Nunez I, Wcisel DJ, Litman RT, Litman GW, Yoder JA. 2016. The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes. Immunogenetics 68: 295-312.

Rousse CA, Olby NJ, Williams K, Harris TL, Griffith EH, Mariani CL, Muñana KR, Early PJ. 2016. Recovery of stepping and coordination in dogs following acute thoracolumbar intervertebral disc herniations. Vet J 213: 59-63.

Rotroff DM, Oki NO, Liang X, Yee SW, Stocker SL, Corum DG, Meisner M, Fiehn O, Motsinger-Reif AA, Giacomini KM, Kaddurah-Daouk R. 2016. Pharmacometabolomic assessment of metformin in non-diabetic, African Americans. Front Pharmacol 7: 135.

Schwartz S, Truglio M, Scott MJ, Fitzsimons HL. 2016. Long-term memory in Drosophila is influenced by the histone deacetylase HDAC4 interacting with the SUMO-conjugating enzyme Ubc9. Genetics 203: 1249-1264.

Serão NV, Kemp RA, Mote BE, Willson P, Harding JC, Bishop SC, Plastow GS, Dekkers JC. 2016. Genetic and genomic basis of antibody response to

porcine reproductive and respiratory syndrome (PRRS) in gilts and sows. Genet Sel Evol 48: 51.

Shah I, Setzer RW, Jack J, Houck KA, Judson RS, Knudsen TB, Liu J, Martin MT, Reif DM, Richard AM, Thomas RS, Crofton KM, Dix DJ, Kavlock RJ. 2016. Using ToxCast™ data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure. Environ Health Perspect 124: 910-919.

Sharpe DM, Langerhans RB, Low-Décarie E, Chapman LJ. 2015. Little evidence for morphological change in a resilient endemic species following the introduction of a novel predator. J Evol Biol 28: 2054-2067.

Skelly DA, Magwene PM, Stone EA. 2016. Sporadic, global linkage disequilibrium between unlinked segregating sites. Genetics 202: 427-437.

Stone EA, Singh ND. 2016. Bias-variance tradeoffs in recombination rate estimation. Genetics 202: 857-859.

Villarino GH, Hu Q, Manrique S, Flores-Vergara M, Sehra B, Robles L, Brumos J, Stepanova AN, Colombo L, Sundberg E, Heber S, Franks RG. 2016. Transcriptomic signature of the SHATTERPROOF2 expression domain reveals the meristematic nature of Arabidopsis gynoecial medial domain. Plant Physiol 171: 42-61.

Vonesch SC, Lamparter D, Mackay TFC, Bergmann S, Hafen E. 2016. Genome-wide analysis reveals novel regulators of growth in Drosophila melanogaster. PLoS Genet 12: e1005616.

Wang GF, Balint-Kurti PJ. 2016. Maize homologs of CCoAOMT and HCT, two key enzymes in lignin biosynthesis, form complexes with the NLR Rp1 protein to modulate the defense response. Plant Physiol 171: 2166-2177.

Zhang G, Huang KC, Xu Z, Tzeng JY, Conneely KN, Guan W, Kang J, Li Y. 2016. Across-platform imputation of DNA methylation levels incorporating nonlocal information using penalized functional regression. Genet Epidemiol 40: 333-340.

Zhang G, Marvel S, Truong L, Tanguay RL, Reif DM. 2016. Aggregate entropy scoring for quantifying activity across endpoints with irregular correlation structure. Reprod Toxicol 62: 92-99.

Zhou K, Yee SW, Seiser EL, van Leeuwen N, Tavendale R, Bennett AJ, Groves CJ, Coleman RL, van der Heijden AA, Beulens JW, de Keyser CE, Zaharenko L, Rotroff DM, Out M, Jablonski KA,

Chen L, Javorský M, Židzik J, Levin AM, Williams LK, Dujic T, Semiz S, Kubo M, Chien HC, Maeda

S, Witte JS, Wu L, Tkáč I, Kooy A, van Schaik RH, Stehouwer CD, Logie L; MetGen Investigators; DPP Investigators; ACCORD Investigators, Sutherland C, Klovins J, Pirags V, Hofman A, Stricker BH, Motsinger-Reif AA, Wagner MJ, Innocenti F, Hart LM, Holman RR, McCarthy MI, Hedderson MM, Palmer CN, Florez JC, Giacomini KM, Pearson ER. 2016. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet 48: 1055-1059.

Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TFC, Anholt RRH. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124: 1062-1070.

Zhou YH, Wright FA. 2016. The projack: a resampling approach to correct for ranking bias in high-throughput studies. Biostatistics17: 54-64.

Zwarts L, Vanden Broeck L, Cappuyns E, Ayroles JF, Magwire MM, Vulsteke V, Clements J, Mackay TFC, Callaerts P. 2015. The genetic basis of natural variation in mushroom body size in Drosophila melanogaster. Nat Commun 6: 10115.

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