@article{nielsen_hsu_zapata iii_ciavarra_zyl_2025, title={Bayesian analysis of the rate of spontaneous malignant mesothelioma among <i>BAP1</i> mutant mice in the absence of asbestos exposure}, volume={15}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-84069-w}, abstractNote={Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Nielsen, Dahlia M. and Hsu, Mei and Zapata III, Michael and Ciavarra, Giovanni and Zyl, Leonel}, year={2025}, month={Jan} }
 @article{sweet_iglesias-carres_ellsworth_carter_nielsen_aylor_tessem_neilson_2025, title={Phenotype variability in diet-induced obesity and response to (−)-epigallocatechin gallate supplementation in a Diversity Outbred mouse cohort: A model for exploring gene x diet interactions for dietary bioactives}, volume={133}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/j.nutres.2024.11.008}, DOI={10.1016/j.nutres.2024.11.008}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Sweet, Michael G. and Iglesias-Carres, Lisard and Ellsworth, Peter N. and Carter, Jared D. and Nielsen, Dahlia M. and Aylor, David L. and Tessem, Jeffery S. and Neilson, Andrew P.}, year={2025}, month={Jan}, pages={78–93} }
 @article{knight_doherty_nielsen_2022, title={Assessing the Nucleotide-Level Impact of Spaceflight Stress using RNA-Sequencing Data}, url={https://doi.org/10.1101/2022.12.01.518235}, DOI={10.1101/2022.12.01.518235}, abstractNote={AbstractUnderstanding the effects of space radiation and microgravity on DNA integrity is critical to assess the impact of long-term spaceflight. However, studying spaceflight’s effect on terrestrial life is difficult. NASA created GeneLab, a public Omics database for spaceflight-related data, to help combat these limitations. While GeneLab has very few DNA-based data sets, transcriptome information is abundant. This study used RNA-Seq data from GeneLab to examine DNA sequence variants linked to spaceflight stress exposure. More mutations were observed in spaceflight samples than in the ground control samples. This increase in variants was not reduced in samples grown under artificial gravity in space, suggesting that microgravity did not significantly affect the amount of DNA damage in this experiment. There was also an increase in transversion mutations, consistent with known forms of radiation-induced damage. This work demonstrates that RNA-Seq data is a useful resource for evaluating DNA damage from spaceflight and provides a baseline for the types of mutations that could be detected.}, author={Knight, Montana S. and Doherty, Colleen J. and Nielsen, Dahlia M.}, year={2022}, month={Dec} }
 @article{ferguson_foster_sherry_magness_nielsen_gookin_2019, title={Interferon-λ3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection}, volume={8}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2019.02.007}, DOI={10.1016/j.jcmgh.2019.02.007}, abstractNote={The epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection.The significance of C parvum-induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies.Immunoneutralization of IFN-λ2/3 in C parvum-infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum-induced loss of barrier function by decreasing paracellular permeability to sodium.These studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.}, number={1}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Ferguson, Sylvia H. and Foster, Derek M. and Sherry, Barbara and Magness, Scott T. and Nielsen, Dahlia M. and Gookin, Jody L.}, year={2019}, pages={1–20} }
 @article{urkasemsin_nielsen_singleton_arepalli_hernandez_agler_olby_2017, title={Genetics of Hereditary Ataxia in Scottish Terriers}, volume={31}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.14738}, DOI={10.1111/jvim.14738}, abstractNote={BackgroundScottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction.ObjectiveTo identify chromosomal regions associated with hereditary ataxia in Scottish Terriers.AnimalsOne hundred and fifty‐three Scottish Terriers were recruited through the Scottish Terrier Club of America.Materials and MethodsProspective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome‐wide mapping was performed using both linkage‐ and association‐based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively.ResultsLinkage and genome‐wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information.Conclusion and Clinical ImportanceThis finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Urkasemsin, G. and Nielsen, D.M. and Singleton, A. and Arepalli, S. and Hernandez, D. and Agler, C. and Olby, N.J.}, year={2017}, month={May}, pages={1132–1139} }
 @article{guo_fudali_gimeno_digennaro_chang_williamson_bird_nielsen_2017, title={Networks Underpinning Symbiosis Revealed Through Cross-Species eQTL Mapping}, volume={206}, ISSN={["1943-2631"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85027059202&partnerID=MN8TOARS}, DOI={10.1534/genetics.117.202531}, abstractNote={AbstractInteractions between species are pervasive among plants, animals, and microbes, and identifying the molecular signals involved is an active area of research..Organisms engage in extensive cross-species molecular dialog, yet the underlying molecular actors are known for only a few interactions. Many techniques have been designed to uncover genes involved in signaling between organisms. Typically, these focus on only one of the partners. We developed an expression quantitative trait locus (eQTL) mapping-based approach to identify cause-and-effect relationships between genes from two partners engaged in an interspecific interaction. We demonstrated the approach by assaying expression of 98 isogenic plants (Medicago truncatula), each inoculated with a genetically distinct line of the diploid parasitic nematode Meloidogyne hapla. With this design, systematic differences in gene expression across host plants could be mapped to genetic polymorphisms of their infecting parasites. The effects of parasite genotypes on plant gene expression were often substantial, with up to 90-fold (P = 3.2 × 10−52) changes in expression levels caused by individual parasite loci. Mapped loci included a number of pleiotropic sites, including one 87-kb parasite locus that modulated expression of >60 host genes. The 213 host genes identified were substantially enriched for transcription factors. We distilled higher-order connections between polymorphisms and genes from both species via network inference. To replicate our results and test whether effects were conserved across a broader host range, we performed a confirmatory experiment using M. hapla-infected tomato. This revealed that homologous genes were similarly affected. Finally, to validate the broader utility of cross-species eQTL mapping, we applied the strategy to data from a Salmonella infection study, successfully identifying polymorphisms in the human genome affecting bacterial expression.}, number={4}, journal={Genetics}, author={Guo, Y. and Fudali, S. and Gimeno, J. and DiGennaro, P. and Chang, S. and Williamson, V.M. and Bird, D.M. and Nielsen, D.M.}, year={2017}, pages={2175–2184} }
 @article{jackson_nielsen_singh_2015, title={Increased exposure to acute thermal stress is associated with a non-linear increase in recombination frequency and an independent linear decrease in fitness in Drosophila}, volume={15}, ISSN={["1471-2148"]}, DOI={10.1186/s12862-015-0452-8}, abstractNote={AbstractBackgroundMeiotic recombination rate has long been known to be phenotypically plastic. How plastic recombination evolves and is maintained remains controversial; though a leading model for the evolution of plastic recombination rests on the tenet that organismal fitness and recombination frequency are negatively correlated. Motivated by the mounting evidence that meiotic recombination frequencies increase in response to stress, here we test for a negative correlation between fitness and recombination frequency. Specifically, the fitness-associated recombination model (FAR) predicts that if stress increases meiotic recombination frequency, then increasing exposure to stressful conditions will yield an increasing magnitude of the recombinational response, while concomitantly decreasing fitness.ResultsWe use heat shock as a stressor to test this prediction inDrosophila melanogaster. We find that increased exposure to heat shock conditions is associated with a non-linear increase in meiotic recombination frequency. We also find an independent effect of heat shock on organismal fitness, with fitness decreasing with increased duration of thermal stress.ConclusionsOur results thus support the foundation of the FAR model for the evolution of plastic recombination. Our data also suggest that modulating recombination frequency is one mechanism by which organisms can rapidly respond to environmental cues and confer increased adaptive potential to their offspring.}, journal={BMC EVOLUTIONARY BIOLOGY}, author={Jackson, Savannah and Nielsen, Dahlia M. and Singh, Nadia D.}, year={2015}, month={Aug} }
 @article{wang_he_strauch_olukolu_nielsen_li_balint-kurti_2015, title={Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response}, volume={169}, number={3}, journal={Plant Physiol}, author={Wang, G. F. and He, Y. and Strauch, R. and Olukolu, B. A. and Nielsen, D. and Li, X. and Balint-Kurti, P. J.}, year={2015}, pages={2230–2243} }
 @article{olukolu_wang_vontimitta_venkata_marla_ji_gachomo_chu_negeri_benson_et al._2014, title={A Genome-Wide Association Study of the Maize Hypersensitive Defense Response Identifies Genes That Cluster in Related Pathways}, volume={10}, ISSN={1553-7404}, url={http://dx.doi.org/10.1371/journal.pgen.1004562}, DOI={10.1371/journal.pgen.1004562}, abstractNote={Much remains unknown of molecular events controlling the plant hypersensitive defense response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Genetic control of the HR is hard to quantify due to its microscopic and rapid nature. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mapped in a population of 3,381 recombinant inbred lines from the maize nested association mapping population. Joint linkage analysis was conducted to identify 32 additive but no epistatic quantitative trait loci (QTL) using a linkage map based on more than 7000 single nucleotide polymorphisms (SNPs). Genome-wide association (GWA) analysis of 26.5 million SNPs was conducted after adjusting for background QTL. GWA identified associated SNPs that colocalized with 44 candidate genes. Thirty-six of these genes colocalized within 23 of the 32 QTL identified by joint linkage analysis. The candidate genes included genes predicted to be in involved programmed cell death, defense response, ubiquitination, redox homeostasis, autophagy, calcium signalling, lignin biosynthesis and cell wall modification. Twelve of the candidate genes showed significant differential expression between isogenic lines differing for the presence of Rp1-D21. Low but significant correlations between HR-related traits and several previously-measured disease resistance traits suggested that the genetic control of these traits was substantially, though not entirely, independent. This study provides the first system-wide analysis of natural variation that modulates the HR response in plants.}, number={8}, journal={PLoS Genetics}, publisher={Public Library of Science (PLoS)}, author={Olukolu, Bode A. and Wang, Guan-Feng and Vontimitta, Vijay and Venkata, Bala P. and Marla, Sandeep and Ji, Jiabing and Gachomo, Emma and Chu, Kevin and Negeri, Adisu and Benson, Jacqueline and et al.}, editor={McDowell, John M.Editor}, year={2014}, month={Aug}, pages={e1004562} }
 @article{dolezal_shu_obrian_nielsen_woloshuk_boston_payne_2014, title={Aspergillus flavus infection induces transcriptional and physical changes in developing maize kernels}, volume={5}, ISSN={1664-302X}, url={http://dx.doi.org/10.3389/fmicb.2014.00384}, DOI={10.3389/fmicb.2014.00384}, abstractNote={Maize kernels are susceptible to infection by the opportunistic pathogen Aspergillus flavus. Infection results in reduction of grain quality and contamination of kernels with the highly carcinogenic mycotoxin, aflatoxin. To understanding host response to infection by the fungus, transcription of approximately 9000 maize genes were monitored during the host-pathogen interaction with a custom designed Affymetrix GeneChip® DNA array. More than 4000 maize genes were found differentially expressed at a FDR of 0.05. This included the up regulation of defense related genes and signaling pathways. Transcriptional changes also were observed in primary metabolism genes. Starch biosynthetic genes were down regulated during infection, while genes encoding maize hydrolytic enzymes, presumably involved in the degradation of host reserves, were up regulated. These data indicate that infection of the maize kernel by A. flavus induced metabolic changes in the kernel, including the production of a defense response, as well as a disruption in kernel development.}, journal={Frontiers in Microbiology}, publisher={Frontiers Media SA}, author={Dolezal, Andrea L. and Shu, Xiaomei and OBrian, Gregory R. and Nielsen, Dahlia M. and Woloshuk, Charles P. and Boston, Rebecca S. and Payne, Gary A.}, year={2014}, month={Jul} }
 @article{agler_nielsen_urkasemsin_singleton_tonomura_sigurdsson_tang_linder_arepalli_hernandez_et al._2014, title={Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24}, volume={10}, number={2}, journal={PLoS Genet}, author={Agler, C. and Nielsen, D. M. and Urkasemsin, G. and Singleton, A. and Tonomura, N. and Sigurdsson, S. and Tang, R. and Linder, K. and Arepalli, S. and Hernandez, D. and et al.}, year={2014}, pages={e1003991} }
 @article{guo_bird_nielsen_2014, title={Improved structural annotation of protein-coding genes in the Meloidogyne hapla genome using RNA-Seq}, volume={3}, ISSN={2162-4054}, url={http://dx.doi.org/10.4161/worm.29158}, DOI={10.4161/worm.29158}, abstractNote={As high-throughput cDNA sequencing (RNA-Seq) is increasingly applied to hypothesis-driven biological studies, the prediction of protein coding genes based on these data are usurping strictly in silico approaches. Compared with computationally derived gene predictions, structural annotation is more accurate when based on biological evidence, particularly RNA-Seq data. Here, we refine the current genome annotation for the Meloidogyne hapla genome utilizing RNA-Seq data. Published structural annotation defines 14 420 protein-coding genes in the M. hapla genome. Of these, 25% (3751) were found to exhibit some incongruence with RNA-Seq data. Manual annotation enabled these discrepancies to be resolved. Our analysis revealed 544 new gene models that were missing from the prior annotation. Additionally, 1457 transcribed regions were newly identified on the ends of as-yet-unjoined contigs. We also searched for trans-spliced leaders, and based on RNA-Seq data, identified genes that appear to be trans-spliced. Four 22-bp trans-spliced leaders were identified using our pipeline, including the known trans-spliced leader, which is the M. hapla ortholog of SL1. In silico predictions of trans-splicing were validated by comparison with earlier results derived from an independent cDNA library constructed to capture trans-spliced transcripts. The new annotation, which we term HapPep5, is publically available at www.hapla.org.}, number={1}, journal={Worm}, publisher={Informa UK Limited}, author={Guo, Yuelong and Bird, David McK and Nielsen, Dahlia M}, year={2014}, month={Jan}, pages={e29158} }
 @article{franck_nielsen_osborne_2013, title={A method for detecting hidden additivity in two-factor unreplicated experiments}, volume={67}, ISSN={0167-9473}, url={http://dx.doi.org/10.1016/j.csda.2013.05.002}, DOI={10.1016/j.csda.2013.05.002}, abstractNote={Assessment of interaction in unreplicated two-factor experiments is a challenging problem that has received considerable attention in the literature. A model is proposed in which the levels of one factor belong in two or more groups. Within each group the effects of the two factors are additive but the groups may interact with the ungrouped factor. This structure is called “hidden additivity” if group membership is latent. To identify plausible groupings a search is performed over the space of all possible configurations, or placement of units into two or more groups. A multiplicity-adjusted all-configurations maximum interaction F (ACMIF) test to detect hidden additivity is developed. The method is illustrated using two data sets taken from the literature and a third taken from a recent study of copy number variation due to lymphoma. A simulation study demonstrates the power of the test for hidden additivity and compares it with other well-known tests from the literature.}, journal={Computational Statistics & Data Analysis}, publisher={Elsevier BV}, author={Franck, Christopher T. and Nielsen, Dahlia M. and Osborne, Jason A.}, year={2013}, month={Nov}, pages={95–104} }
 @article{richards_motsinger-reif_chen_fedoriw_fan_nielsen_small_thomas_smith_dave_et al._2013, title={Gene Profiling of Canine B-Cell Lymphoma Reveals Germinal Center and Postgerminal Center Subtypes with Different Survival Times, Modeling Human DLBCL}, volume={73}, ISSN={0008-5472 1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.CAN-12-3546}, DOI={10.1158/0008-5472.can-12-3546}, abstractNote={Abstract
               Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-κB pathway genes, mirroring human activated B-cell (ABC)–type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials. Cancer Res; 73(16); 5029–39. ©2013 AACR.}, number={16}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Richards, K. L. and Motsinger-Reif, A. A. and Chen, H.-W. and Fedoriw, Y. and Fan, C. and Nielsen, D. M. and Small, G. W. and Thomas, R. and Smith, C. and Dave, S. S. and et al.}, year={2013}, month={Jun}, pages={5029–5039} }
 @article{su_nielsen_zhu_richards_suter_breen_motsinger-reif_osborne_2013, title={Gene selection and cancer type classification of diffuse large-B-cell lymphoma using a bivariate mixture model for two-species data}, volume={7}, journal={Hum Genomics}, author={Su, Y. and Nielsen, D. and Zhu, L. and Richards, K. and Suter, S. and Breen, M. and Motsinger-Reif, A. and Osborne, J.}, year={2013}, pages={2} }
 @article{supple_hines_dasmahapatra_lewis_nielsen_lavoie_ray_salazar_owen mcmillan_counterman_2013, title={Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies}, volume={23}, ISSN={["1549-5469"]}, DOI={10.1101/gr.150615.112}, abstractNote={Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations.}, number={8}, journal={GENOME RESEARCH}, author={Supple, Megan A. and Hines, Heather M. and Dasmahapatra, Kanchon K. and Lewis, James J. and Nielsen, Dahlia M. and Lavoie, Christine and Ray, David A. and Salazar, Camilo and Owen McMillan, W. and Counterman, Brian A.}, year={2013}, month={Aug}, pages={1248–1257} }
 @article{dolezal_obrian_nielsen_woloshuk_boston_payne_2013, title={Localization, morphology and transcriptional profile of Aspergillus flavus during seed colonization}, volume={14}, ISSN={["1364-3703"]}, DOI={10.1111/mpp.12056}, abstractNote={SummaryAspergillus flavus is an opportunistic fungal pathogen that infects maize kernels pre‐harvest, creating major human health concerns and causing substantial agricultural losses. Improved control strategies are needed, yet progress is hampered by the limited understanding of the mechanisms of infection. A series of studies were designed to investigate the localization, morphology and transcriptional profile of A. flavus during internal seed colonization. Results from these studies indicate that A. flavus is capable of infecting all tissues of the immature kernel by 96 h after infection. Mycelia were observed in and around the point of inoculation in the endosperm and were found growing down to the germ. At the endosperm–germ interface, hyphae appeared to differentiate and form a biofilm‐like structure that surrounded the germ. The exact nature of this structure remains unclear, but is discussed. A custom‐designed A. flavus Affymetrix GeneChip® microarray was used to monitor genome‐wide transcription during pathogenicity. A total of 5061 genes were designated as being differentially expressed. Genes encoding secreted enzymes, transcription factors and secondary metabolite gene clusters were up‐regulated and considered to be potential effector molecules responsible for disease in the kernel. Information gained from this study will aid in the development of strategies aimed at preventing or slowing down A. flavus colonization of the maize kernel.}, number={9}, journal={MOLECULAR PLANT PATHOLOGY}, author={Dolezal, Andrea L. and Obrian, Gregory R. and Nielsen, Dahlia M. and Woloshuk, Charles P. and Boston, Rebecca S. and Payne, Gary A.}, year={2013}, month={Dec}, pages={898–909} }
 @article{angstadt_motsinger-reif_thomas_kisseberth_couto_duval_nielsen_modiano_breen_2011, title={Characterization of Canine Osteosarcoma by Array Comparative Genomic Hybridization and RT-qPCR: Signatures of Genomic Imbalance in Canine Osteosarcoma Parallel the Human Counterpart}, volume={50}, ISSN={["1098-2264"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80052683142&partnerID=MN8TOARS}, DOI={10.1002/gcc.20908}, abstractNote={AbstractOsteosarcoma (OS) is the most commonly diagnosed malignant bone tumor in humans and dogs, characterized in both species by extremely complex karyotypes exhibiting high frequencies of genomic imbalance. Evaluation of genomic signatures in human OS using array comparative genomic hybridization (aCGH) has assisted in uncovering genetic mechanisms that result in disease phenotype. Previous low‐resolution (10–20 Mb) aCGH analysis of canine OS identified a wide range of recurrent DNA copy number aberrations, indicating extensive genomic instability. In this study, we profiled 123 canine OS tumors by 1 Mb‐resolution aCGH to generate a dataset for direct comparison with current data for human OS, concluding that several high frequency aberrations in canine and human OS are orthologous. To ensure complete coverage of gene annotation, we identified the human refseq genes that map to these orthologous aberrant dog regions and found several candidate genes warranting evaluation for OS involvement. Specifically, subsequenct FISH and qRT‐PCR analysis of RUNX2, TUSC3, and PTEN indicated that expression levels correlated with genomic copy number status, showcasing RUNX2 as an OS associated gene and TUSC3 as a possible tumor suppressor candidate. Together these data demonstrate the ability of genomic comparative oncology to identify genetic abberations which may be important for OS progression. Large scale screening of genomic imbalance in canine OS further validates the use of the dog as a suitable model for human cancers, supporting the idea that dysregulation discovered in canine cancers will provide an avenue for complementary study in human counterparts. © 2011 Wiley‐Liss, Inc.}, number={11}, journal={GENES CHROMOSOMES & CANCER}, author={Angstadt, Andrea Y. and Motsinger-Reif, Alison and Thomas, Rachael and Kisseberth, William C. and Couto, C. Guillermo and Duval, Dawn L. and Nielsen, Dahlia M. and Modiano, Jaime F. and Breen, Matthew}, year={2011}, month={Nov}, pages={859–874} }
 @article{reese_payne_nielsen_woloshuk_2011, title={Gene Expression profile and response to maize kernels by Aspergillus flavus}, volume={101}, ISSN={["1943-7684"]}, DOI={10.1094/PHYTO-09-10-0261}, abstractNote={ Aspergillus flavus causes an ear rot of maize, often resulting in the production of aflatoxin, a potent liver toxin and carcinogen that impacts the health of humans and animals. Many aspects of kernel infection and aflatoxin biosynthesis have been studied but the precise effects of the kernel environment on A. flavus are poorly understood. The goal of this research was to study the fungal response to the kernel environment during colonization. Gene transcription in A. flavus was analyzed by microarrays after growth on kernels of the four developmental stages: blister (R2), milk (R3), dough (R4), and dent (R5). Five days after inoculation, total RNA was isolated from kernels and hybridized to Affymetrix Gene Chip arrays containing probes representing 12,834 A. flavus genes. Statistical comparisons of the expression profile data revealed significant differences that included unique sets of upregulated genes in each kernel stage and six patterns of expression over the four stages. Among the genes expressed in colonized dent kernels were a phytase gene and six putative genes involved in zinc acquisition. Disruption of the phytase gene phy1 resulted in reduced growth on medium containing phytate as the sole source of phosphate. Furthermore, growth of the mutant (Δphy1) was 20% of the wild-type strain when wound inoculated into maize ears. In contrast, no difference was detected in the amount of aflatoxin produced relative to fungal growth, indicating that phy1 does not affect aflatoxin production. The study revealed the genome-wide effects of immature maize kernels on A. flavus and suggest that phytase has a role in pathogenesis. }, number={7}, journal={Phytopathology}, author={Reese, B.N. and Payne, G.A. and Nielsen, D.M. and Woloshuk, C.P.}, year={2011}, pages={797–804} }
 @article{salzmann_olivry_nielsen_paps_harris_olby_2011, title={Genome-wide linkage study of atopic dermatitis in West Highland White Terriers}, volume={12}, ISSN={1471-2156}, url={http://dx.doi.org/10.1186/1471-2156-12-37}, DOI={10.1186/1471-2156-12-37}, abstractNote={AbstractBackgroundCanine atopic dermatitis (AD) is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT). In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder.ResultsBlood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2). Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7.ConclusionsThe study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.}, number={1}, journal={BMC Genetics}, publisher={Springer Science and Business Media LLC}, author={Salzmann, Cary A and Olivry, Thierry JM and Nielsen, Dahlia M and Paps, Judith S and Harris, Tonya L and Olby, Natasha J}, year={2011}, pages={37} }
 @article{counterman_araujo-perez_hines_baxter_morrison_lindstrom_papa_ferguson_joron_ffrench-constant_et al._2010, title={Genomic Hotspots for Adaptation: The Population Genetics of Müllerian Mimicry in Heliconius erato}, volume={6}, ISSN={1553-7404}, url={http://dx.doi.org/10.1371/journal.pgen.1000796}, DOI={10.1371/journal.pgen.1000796}, abstractNote={Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as “supergenes.” Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations.}, number={2}, journal={PLoS Genetics}, publisher={Public Library of Science (PLoS)}, author={Counterman, Brian A. and Araujo-Perez, Felix and Hines, Heather M. and Baxter, Simon W. and Morrison, Clay M. and Lindstrom, Daniel P. and Papa, Riccardo and Ferguson, Laura and Joron, Mathieu and ffrench-Constant, Richard H. and et al.}, editor={Nachman, Michael W.Editor}, year={2010}, month={Feb}, pages={e1000796} }
 @article{reininga_nielsen_purugganan_2009, title={Functional and geographical differentiation of candidate balanced polymorphisms in Arabidopsis thaliana}, volume={18}, ISSN={["1365-294X"]}, DOI={10.1111/j.1365-294X.2009.04206.x}, abstractNote={AbstractMolecular population genetic analysis of three chromosomal regions in Arabidopsis thaliana suggested that balancing selection might operate to maintain variation at three novel candidate adaptive trait genes, including SOLUBLE STARCH SYNTHASE I (SSI), PLASTID TRANSCRIPTIONALLY ACTIVE 7(PTAC7), and BELL‐LIKE HOMEODOMAIN 10 (BLH10). If balanced polymorphisms are indeed maintained at these loci, then we would expect to observe functional variation underlying the previously detected signatures of selection. We observe multiple replacement polymorphisms within and in the 32 amino acids just upstream of the protein–protein interacting BELL domain at the BLH10 locus. While no clear protein sequence differences are found between allele types in SSI and PTAC7, these two genes show evidence for allele‐specific variation in expression levels. Geographical patterns of allelic differentiation seem consistent with population stratification in this species and a significant longitudinal cline was observed at all three candidate loci. These data support a hypothesis of balancing selection at all three candidate loci and provide a basis for more detailed functional work by identifying possible functional differences that might be selectively maintained.}, number={13}, journal={MOLECULAR ECOLOGY}, author={Reininga, Jennifer M. and Nielsen, Dahlia and Purugganan, Michael D.}, year={2009}, month={Jul}, pages={2844–2855} }
 @article{bushel_nielsen_tong_2009, title={Proceedings of the First International Conference on Toxicogenomics Integrated with Environmental Sciences (TIES-2007)}, volume={3}, ISSN={1753-6561}, url={http://dx.doi.org/10.1186/1753-6561-3-s2-s1}, DOI={10.1186/1753-6561-3-s2-s1}, abstractNote={The First International Conference on Toxicogenomics Integrated with Environmental Sciences (TIES-2007) was held at the North Carolina State University McKimmon Center in Raleigh, North Carolina on October 25th and 26th, 2007. Based on the presentations at the conference and the commitment or interest of the presenters to contribute a manuscript of their research, we compiled this collection of articles as proceedings of the conference and an in-depth topical review of the utility of bioinformatics in the fields of toxicogenomics and environmental genomics.}, number={S2}, journal={BMC Proceedings}, publisher={Springer Science and Business Media LLC}, author={Bushel, Pierre R and Nielsen, Dahlia and Tong, Weida}, year={2009}, month={Mar} }
 @article{nielsen_suchindran_smith_2008, title={Does strong linkage disequilibrium guarantee redundant association results?}, volume={32}, ISSN={0741-0395 1098-2272}, url={http://dx.doi.org/10.1002/gepi.20328}, DOI={10.1002/gepi.20328}, abstractNote={AbstractA substantial amount of effort has been expended recently towards the identification and evaluation of tag single nucleotide polymorphisms; markers that, due to linkage disequilibrium (LD) patterns in the genome, are able to act as “proxies” for other polymorphic sites. As such, these tag markers are assumed to capture, on their own, a large proportion of the genetic variation contributed by a much greater number of polymorphic sites. One important consequence of this is the potential ability to reduce the cost of genotyping in an association study without a corresponding loss of power. This application carries an implicit assumption that strong LD between markers implies high correlation between the accompanying association test results, so that once a tag marker is evaluated for association, its outcome will be representative of all the other markers for which it serves as proxy. We examined this assumption directly. We find that in the null hypothesis situation, where there is no association between the markers and the phenotype, the relationship between LD and the correlation between association test outcomes is clear, though it is not always ideal. In the alternative case, when genetic association does exist in the region, the relationship becomes much more complex. Here, reasonably high LD between markers does not necessarily imply that the association test result of one marker is a direct substitute for that of the other. In these cases, eliminating one of these markers from the set to be genotyped in an association study will lead to a reduction in overall power. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.}, number={6}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Nielsen, Dahlia M. and Suchindran, Sunil and Smith, Christopher P.}, year={2008}, month={Sep}, pages={546–552} }
 @inproceedings{olby_harris_mehta_breen_thomas_myers_nielsen_2008, title={Linkage Analysis in American Staffordshire Terriers with Hereditary Cerebellar Cortical Degeneration}, volume={22}, number={3}, booktitle={Journal of Veterinary Internal Medicine}, author={Olby, N.J. and Harris, T. and Mehta, P.M. and Breen, M. and Thomas, R. and Myers, R. and Nielsen, D.}, year={2008}, pages={723–724} }
 @article{smith_robertson_yates_nielsen_brown_dean_payne_2008, title={The effect of temperature on Natural Antisense Transcript (NAT) expression in Aspergillus flavus}, volume={54}, ISSN={0172-8083 1432-0983}, url={http://dx.doi.org/10.1007/s00294-008-0215-9}, DOI={10.1007/s00294-008-0215-9}, abstractNote={Naturally occurring Antisense Transcripts (NATs) compose an emerging group of regulatory RNAs. These regulatory elements appear in all organisms examined, but little is known about global expression of NATs in fungi. Analysis of currently available EST sequences suggests that 352 cis NATs are present in Aspergillus flavus. An Affymetrix GeneChip microarray containing probes for these cis NATs, as well as all predicted genes in A. flavus, allowed a whole genome expression analysis of these elements in response to two ecologically important temperatures for the fungus. RNA expression analysis showed that 32 NATs and 2,709 genes were differentially expressed between 37 degrees C, the optimum temperature for growth, and 28 degrees C, the conducive temperature for the biosynthesis of aflatoxin (AF) and many other secondary metabolites. These NATs correspond to sense genes with diverse functions including transcription initiation, carbohydrate processing and binding, temperature sensitive morphogenesis, and secondary metabolism. This is the first report of a whole genome transcriptional analysis of NAT expression in a fungus.}, number={5}, journal={Current Genetics}, publisher={Springer Science and Business Media LLC}, author={Smith, Carrie A. and Robertson, Dominique and Yates, Bethan and Nielsen, Dahlia M. and Brown, Doug and Dean, Ralph A. and Payne, Gary A.}, year={2008}, month={Sep}, pages={241–269} }
 @article{schaff_nielsen_smith_scholl_bird_2007, title={Comprehensive Transcriptome Profiling in Tomato Reveals a Role for Glycosyltransferase in Mi-Mediated Nematode Resistance}, volume={144}, ISSN={0032-0889 1532-2548}, url={http://dx.doi.org/10.1104/pp.106.090241}, DOI={10.1104/pp.106.090241}, abstractNote={Abstract
               Root-knot nematode (RKN; Meloidogyne spp.) is a major crop pathogen worldwide. Effective resistance exists for a few plant species, including that conditioned by Mi in tomato (Solanum lycopersicum). We interrogated the root transcriptome of the resistant (Mi+) and susceptible (Mi–) cultivars ‘Motelle’ and ‘Moneymaker,’ respectively, during a time-course infection by the Mi-susceptible RKN species Meloidogyne incognita and the Mi-resistant species Meloidogyne hapla. In the absence of RKN infection, only a single significantly regulated gene, encoding a glycosyltransferase, was detected. However, RKN infection influenced the expression of broad suites of genes; more than half of the probes on the array identified differential gene regulation between infected and uninfected root tissue at some stage of RKN infection. We discovered 217 genes regulated during the time of RKN infection corresponding to establishment of feeding sites, and 58 genes that exhibited differential regulation in resistant roots compared to uninfected roots, including the glycosyltransferase. Using virus-induced gene silencing to silence the expression of this gene restored susceptibility to M. incognita in ‘Motelle,’ indicating that this gene is necessary for resistance to RKN. Collectively, our data provide a picture of global gene expression changes in roots during compatible and incompatible associations with RKN, and point to candidates for further investigation.}, number={2}, journal={Plant Physiology}, publisher={American Society of Plant Biologists (ASPB)}, author={Schaff, Jennifer E. and Nielsen, Dahlia M. and Smith, Chris P. and Scholl, Elizabeth H. and Bird, David McK.}, year={2007}, month={Apr}, pages={1079–1092} }
 @article{cary_obrian_nielsen_nierman_harris-coward_yu_bhatnagar_cleveland_payne_calvo_2007, title={Elucidation of veA-dependent genes associated with aflatoxin and sclerotial production in Aspergillus flavus by functional genomics}, volume={76}, ISSN={0175-7598 1432-0614}, url={http://dx.doi.org/10.1007/s00253-007-1081-y}, DOI={10.1007/s00253-007-1081-y}, abstractNote={The aflatoxin-producing fungi, Aspergillus flavus and A. parasiticus, form structures called sclerotia that allow for survival under adverse conditions. Deletion of the veA gene in A. flavus and A. parasiticus blocks production of aflatoxin as well as sclerotial formation. We used microarray technology to identify genes differentially expressed in wild-type veA and veA mutant strains that could be involved in aflatoxin production and sclerotial development in A. flavus. The DNA microarray analysis revealed 684 genes whose expression changed significantly over time; 136 of these were differentially expressed between the two strains including 27 genes that demonstrated a significant difference in expression both between strains and over time. A group of 115 genes showed greater expression in the wild-type than in the veA mutant strain. We identified a subgroup of veA-dependent genes that exhibited time-dependent expression profiles similar to those of known aflatoxin biosynthetic genes or that were candidates for involvement in sclerotial production in the wild type.}, number={5}, journal={Applied Microbiology and Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Cary, J. W. and OBrian, G. R. and Nielsen, D. M. and Nierman, W. and Harris-Coward, P. and Yu, J. and Bhatnagar, D. and Cleveland, T. E. and Payne, G. A. and Calvo, A. M.}, year={2007}, month={Jul}, pages={1107–1118} }
 @article{yu_pressoir_briggs_vroh bi_yamasaki_doebley_mcmullen_gaut_nielsen_holland_et al._2006, title={A unified mixed-model method for association mapping that accounts for multiple levels of relatedness}, volume={38}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/ng1702}, DOI={10.1038/ng1702}, abstractNote={As population structure can result in spurious associations, it has constrained the use of association studies in human and plant genetics. Association mapping, however, holds great promise if true signals of functional association can be separated from the vast number of false signals generated by population structure. We have developed a unified mixed-model approach to account for multiple levels of relatedness simultaneously as detected by random genetic markers. We applied this new approach to two samples: a family-based sample of 14 human families, for quantitative gene expression dissection, and a sample of 277 diverse maize inbred lines with complex familial relationships and population structure, for quantitative trait dissection. Our method demonstrates improved control of both type I and type II error rates over other methods. As this new method crosses the boundary between family-based and structured association samples, it provides a powerful complement to currently available methods for association mapping.}, number={2}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Yu, Jianming and Pressoir, Gael and Briggs, William H and Vroh Bi, Irie and Yamasaki, Masanori and Doebley, John F and McMullen, Michael D and Gaut, Brandon S and Nielsen, Dahlia M and Holland, James B and et al.}, year={2006}, pages={203–208} }
 @article{stafford-smith_podgoreanu_swaminathan_phillips-bute_mathew_hauser_winn_milano_nielsen_smith_et al._2005, title={Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery}, volume={45}, ISSN={0272-6386}, url={http://dx.doi.org/10.1053/j.ajkd.2004.11.021}, DOI={10.1053/j.ajkd.2004.11.021}, abstractNote={BACKGROUND
Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery.


METHODS
One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury.


RESULTS
A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005).


CONCLUSION
In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.}, number={3}, journal={American Journal of Kidney Diseases}, publisher={Elsevier BV}, author={Stafford-Smith, Mark and Podgoreanu, Mihai and Swaminathan, Madhav and Phillips-Bute, Barbara and Mathew, Joseph P. and Hauser, Elizabeth H. and Winn, Michelle P. and Milano, Carmelo and Nielsen, Dahlia M. and Smith, Mike and et al.}, year={2005}, month={Mar}, pages={519–530} }
 @article{grocott_white_morris_podgoreanu_mathew_nielsen_schwinn_newman_2005, title={Genetic Polymorphisms and the Risk of Stroke After Cardiac Surgery}, volume={36}, ISSN={0039-2499 1524-4628}, url={http://dx.doi.org/10.1161/01.str.0000177482.23478.dc}, DOI={10.1161/01.str.0000177482.23478.dc}, abstractNote={
            
              Background and Purpose—
            
            Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery.
          
          
            
              Methods—
            
            Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies.
          
          
            
              Results—
            
            A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3′UTR 1846C/T) and interleukin-6 (IL-6; −174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1;
            P
            =0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (
            P
            =0.0020).
          
          
            
              Conclusions—
            
            We demonstrate that common genetic variants of CRP (3′UTR 1846C/T) and IL-6 (−174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post–cardiac surgery stroke.
          }, number={9}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Grocott, Hilary P. and White, William D. and Morris, Richard W. and Podgoreanu, Mihai V. and Mathew, Joseph P. and Nielsen, Dahlia M. and Schwinn, Debra A. and Newman, Mark F.}, year={2005}, month={Sep}, pages={1854–1858} }
 @article{weir_cardon_anderson_nelson_hill_2005, title={Measures of human population structure show heterogeneity among genomic regions}, volume={15}, ISSN={1088-9051}, url={http://dx.doi.org/10.1101/gr.4398405}, DOI={10.1101/gr.4398405}, abstractNote={Estimates of genetic population structure (FST) were constructed from all autosomes in two large SNP data sets. The Perlegen data set contains genotypes on ∼1 million SNPs segregating in all three samples of Americans of African, Asian, and European descent; and the Phase I HapMap data set contains genotypes on ∼0.6 million SNPs segregating in all four samples from specific Caucasian, Chinese, Japanese, and Yoruba populations. Substantial heterogeneity of FST values was found between segments within chromosomes, although there was similarity between the two data sets. There was also substantial heterogeneity among population-specific FST values, with the relative sizes of these values often changing along each chromosome. Population-structure estimates are often used as indicators of natural selection, but the analyses presented here show that individual-marker estimates are too variable to be useful. There is inherent variation in these statistics because of variation in genealogy even among neutral loci, and values at pairs of loci are correlated to an extent that reflects the linkage disequilibrium between them. Furthermore, it may be that the best indications of selection will come from population-specific FST values rather than the usually reported population-average values.}, number={11}, journal={Genome Research}, publisher={Cold Spring Harbor Laboratory}, author={Weir, B. S. and Cardon, L.R. and Anderson, A.D. and Nelson, D.M. and Hill, W.G.}, year={2005}, month={Nov}, pages={1468–1476} }
 @article{weir_cardon_anderson_nielsen_hill_2005, title={Measures of human population structure show heterogeneity among genomic regions}, volume={15}, number={11}, journal={Genome Res}, author={Weir, B. S. and Cardon, L. R. and Anderson, A. D. and Nielsen, D. M. and Hill, W. G.}, year={2005}, pages={1468–1476} }
 @article{nielsen_ehm_zaykin_weir_2004, title={Effect of Two- and Three-Locus Linkage Disequilibrium on the Power to Detect Marker/Phenotype Associations}, volume={168}, ISSN={0016-6731 1943-2631}, url={http://dx.doi.org/10.1534/genetics.103.022335}, DOI={10.1534/genetics.103.022335}, abstractNote={AbstractThere has been much recent interest in describing the patterns of linkage disequilibrium (LD) along a chromosome. Most empirical studies that have examined this issue have concentrated on LD between collections of pairs of markers and have not considered the joint effect of a group of markers beyond these pairwise connections. Here, we examine many different patterns of LD defined by both pairwise and joint multilocus LD terms. The LD patterns we considered were chosen in part by examining those seen in real data. We examine how changes in these patterns affect the power to detect association when performing single-marker and haplotype-based case-control tests, including a novel haplotype test based on contrasting LD between affected and unaffected individuals. Through our studies we find that differences in power between single-marker tests and haplotype-based tests in general do not appear to be large. Where moderate to high levels of multilocus LD exist, haplotype tests tend to be more powerful. Single-marker tests tend to prevail when pairwise LD is high. For moderate pairwise values and weak multilocus LD, either testing strategy may come out ahead, although it is also quite likely that neither has much power.}, number={2}, journal={Genetics}, publisher={Genetics Society of America}, author={Nielsen, Dahlia M. and Ehm, Margaret G. and Zaykin, Dmitri V. and Weir, Bruce S.}, year={2004}, month={Oct}, pages={1029–1040} }
 @inproceedings{nielsen_2004, place={Berlin, Heidelberg}, series={Lecture Notes in Computer Science}, title={Multi-locus Linkage Disequilibrium and Haplotype-Based Tests of Association}, ISBN={9783540212492 9783540247197}, ISSN={0302-9743 1611-3349}, url={http://dx.doi.org/10.1007/978-3-540-24719-7_19}, DOI={10.1007/978-3-540-24719-7_19}, abstractNote={The hope behind association mapping is to use linkage disequilibrium (LD) as an indicator of proximity of a marker to a susceptibility locus. This follows from the expectation that marker-phenotype association is proportional to linkage disequilibrium, which is inversely related to recombination. If there are more than two alleles at a locus affecting risk, the association statistic is instead a weighted sum of linkage disequilibria and genotypic susceptibilities. There is no longer a simple relationship, even in expectation, with recombination. These results extend to marker haplotypes. In addition to the pairwise association terms of the single marker tests, marker haplotype associations depend on the weighted sum of multi-locus disequilibria and genotypic susceptibilities. Several tests of haplotype association are presented here, along with a comparison of these tests within different LD contexts.}, booktitle={Computational Methods for SNPs and Haplotype Inference}, publisher={Springer}, author={Nielsen, Dahlia}, year={2004}, pages={139–139}, collection={Lecture Notes in Computer Science} }
 @article{leipzig_nielsen_heber_2004, title={The Splicing Graph – A Tool for Visualising Gene Structure and Alternative Splicing}, journal={Future Drug Discovery}, author={Leipzig, J. and Nielsen, D.M. and Heber, S.}, year={2004}, pages={62–65} }
 @article{czika_weir_edwards_thompson_nielsen_brocklebank_zinkus_martin_nobler_2001, title={Applying Data Mining Techniques to the Mapping of Complex Disease Genes}, volume={21}, ISSN={0741-0395}, url={http://dx.doi.org/10.1002/gepi.2001.21.s1.s435}, DOI={10.1002/gepi.2001.21.s1.s435}, abstractNote={The simulated sequence data for the Genetic Analysis Workshop 12 were analyzed using data mining techniques provided by SAS ENTERPRISE MINERTM Release 4.0 in addition to traditional statistical tests for linkage and association of genetic markers with disease status. We examined two ways of combining these approaches to make use of the covariate data along with the genotypic data. The result of incorporating data mining techniques with more classical methods is an improvement in the analysis, both by correctly classifying the affection status of more individuals and by locating more single nucleotide polymorphisms related to the disease, relative to analyses that use classical methods alone. © 2001 Wiley‐Liss, Inc.}, number={S1}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Czika, W.A. and Weir, B.S. and Edwards, S.R. and Thompson, R.W. and Nielsen, D.M. and Brocklebank, J.C. and Zinkus, C. and Martin, E.R. and Nobler, K.E.}, year={2001}, pages={S435–S440} }
 @article{nielsen_weir_2001, title={Association Studies under General Disease Models}, volume={60}, ISSN={0040-5809}, url={http://dx.doi.org/10.1006/tpbi.2001.1539}, DOI={10.1006/tpbi.2001.1539}, abstractNote={There is great expectation that the levels of association found between genetic markers and disease status will play a role in the location of disease genes. This expectation follows from regarding association as being proportional to linkage disequilibrium and therefore inversely related to recombination value. For disease genes with more than two alleles, the association measure is instead a weighted average of linkage disequilibria, with the weights depending on allele frequencies and genotype susceptibilities at the disease loci. There is no longer a simple relationship, even in expectation, with recombination. We adopt a general framework to examine association mapping methods which helps to clarify the nature of case-control and transmission/disequilibrium-type tests and reveals the relationship between measures of association and coefficients of linkage disequilibrium. In particular, we can show the consequences of additive and nonadditive effects at the trait locus on the behavior of these tests. These concepts have a natural extension to marker haplotypes. The association of two-locus marker haplotypes with disease phenotype depends on a weighted average of three-locus disequilibria (two markers with each disease locus). It is likely that these two-marker analyses will provide additional information in association mapping studies.}, number={3}, journal={Theoretical Population Biology}, publisher={Elsevier BV}, author={Nielsen, Dahlia M. and Weir, B.S.}, year={2001}, month={Nov}, pages={253–263} }
 @article{nielsen_zaykin_2001, title={Association mapping: where we’ve been, where we’re going}, volume={1}, DOI={10.1586/14737159.1.3.334}, abstractNote={This paper provides a review of recent work in the area of marker-phenotype association studies, specifically as used for localizing – or mapping – genes affecting a trait of interest. We describe the basis of association mapping and discuss a number of the commonly used techniques. We have also included references to various papers that have evaluated the use of these methods.}, number={3}, journal={Expert Review of Molecular Diagnostics}, author={Nielsen, D.M. and Zaykin, D.}, year={2001}, pages={334–342} }
 @article{thornsberry_goodman_doebley_kresovich_nielsen_buckler_2001, title={Dwarf8 polymorphisms associate with variation in flowering time}, volume={28}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/90135}, DOI={10.1038/90135}, abstractNote={Historically, association tests have been used extensively in medical genetics, but have had virtually no application in plant genetics. One obstacle to their application is the structured populations often found in crop plants, which may lead to nonfunctional, spurious associations. In this study, statistical methods to account for population structure were extended for use with quantitative variation and applied to our evaluation of maize flowering time. Mutagenesis and quantitative trait locus (QTL) studies suggested that the maize gene Dwarf8 might affect the quantitative variation of maize flowering time and plant height. The wheat orthologs of this gene contributed to the increased yields seen in the 'Green Revolution' varieties. We used association approaches to evaluate Dwarf8 sequence polymorphisms from 92 maize inbred lines. Population structure was estimated using a Bayesian analysis of 141 simple sequence repeat (SSR) loci. Our results indicate that a suite of polymorphisms associate with differences in flowering time, which include a deletion that may alter a key domain in the coding region. The distribution of nonsynonymous polymorphisms suggests that Dwarf8 has been a target of selection.}, number={3}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Thornsberry, Jeffry M. and Goodman, Major M. and Doebley, John and Kresovich, Stephen and Nielsen, Dahlia and Buckler, Edward S.}, year={2001}, month={Jul}, pages={286–289} }
 @article{thomas_borecki_thomson_weiss_almasy_blangero_nielsen_terwilliger_zaykin_maccluer_2001, title={Evolution of the Simulated Data Problem}, volume={21}, ISSN={0741-0395}, url={http://dx.doi.org/10.1002/gepi.2001.21.s1.s325}, DOI={10.1002/gepi.2001.21.s1.s325}, abstractNote={The simulated data problem was designed via an interactive process by the Simulation Problem Organizing Committee and the selected data simulators. Based on discussions at the previous Genetic Analysis Workshop, many of the features of previous simulation problems, such as a complex disease, genome scan, and replication, were retained and in addition, a population genetics model was used to generate the simulated genes. We describe the process that was used to structure the problem and summarize the discussions about many of the scientific issues that were considered. © 2001 Wiley‐Liss, Inc.}, number={S1}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Thomas, Duncan C. and Borecki, Ingrid B. and Thomson, Glenys and Weiss, Ken and Almasy, Laura and Blangero, John and Nielsen, Dahlia and Terwilliger, Joseph and Zaykin, Dmitri and MacCluer, Jean}, year={2001}, pages={S325–S331} }
 @article{almasy_terwilliger_nielsen_dyer_zaykin_blangero_2001, title={GAW12: Simulated Genome Scan, Sequence, and Family Data for a Common Disease}, volume={21}, ISSN={0741-0395}, url={http://dx.doi.org/10.1002/gepi.2001.21.s1.s332}, DOI={10.1002/gepi.2001.21.s1.s332}, abstractNote={The Genetic Analysis Workshop (GAW) 12 simulated data involves a common disease defined by imposing a threshold on a quantitative liability distribution. Associated with the disease are five quantitative risk factors, a quantitative environmental exposure, and a dichotomous environmental variable. Age at disease onset and household membership were also simulated. Genotype data, including 2,855 microsatellites on 22 autosomes, were simulated for 1,497 individuals in 23 families. Phenotype data and sequence data for seven candidate genes were provided for 1,000 of these indiviudals who were “living” and available for study. Data were simulated for 50 replicate samples in each of two populations, a general population and a population isolate formed from a small group of founders. © 2001 Wiley‐Liss, Inc.}, number={S1}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Almasy, Laura and Terwilliger, Joseph D. and Nielsen, Dahlia and Dyer, Thomas D. and Zaykin, Dmitri and Blangero, John}, year={2001}, pages={S332–S338} }
 @article{nielsen_weir_1999, title={A classical setting for associations between markers and loci 
affecting quantitative traits}, volume={74}, ISSN={0016-6723 1469-5073}, url={http://dx.doi.org/10.1017/s0016672399004231}, DOI={10.1017/s0016672399004231}, abstractNote={We examine the relationships between a genetic marker and a locus affecting a quantitative trait 
by decomposing the genetic effects of the marker locus into additive and dominance effects under a 
classical genetic model. We discuss the structure of the associations between the marker and the 
trait locus, paying attention to non-random union of gametes, multiple alleles at the marker and 
trait loci, and non-additivity of allelic effects at the trait locus. We consider that this greater-than-usual level of generality leads to additional insights, in a way reminiscent of Cockerham's 
decomposition of genetic variance into five terms: three terms in addition to the usual additive and 
dominance terms. Using our framework, we examine several common tests of association between 
a marker and a trait.}, number={3}, journal={Genetical Research}, publisher={Cambridge University Press (CUP)}, author={Nielsen, Dahlia M. and Weir, B. S.}, year={1999}, month={Dec}, pages={271–277} }
 @article{cockett_shay_beever_nielsen_albretsen_georges_peterson_stephens_vernon_timofeevskaia_et al._1999, title={Localization of the locus causing Spider Lamb Syndrome to the distal end of ovine Chromosome 6}, volume={10}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/s003359900938}, DOI={10.1007/s003359900938}, abstractNote={Spider Lamb Syndrome (SLS) is a semi-lethal congenital disorder, causing severe skeletal abnormalities in sheep. The syndrome has now been disseminated into several sheep breeds in the United States, Canada, and Australia. The mode of inheritance for SLS is autosomal recessive, making the identification and culling of carrier animals difficult due to their normal phenotype. Two large pedigrees segregating for the SLS mutation were established, and a genome scan with genetic markers from previously published genome maps of cattle and sheep was used to map the locus causing SLS. Genetic linkage between SLS and several microsatellite markers, OarJMP8, McM214, OarJMP12, and BL1038, was detected, thereby mapping the SLS locus to the telomeric end of ovine Chromosome (Chr) 6. Alignment of ovine Chr 6 with its evolutionary ortholog, human Chr 4, revealed a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3).}, number={1}, journal={Mammalian Genome}, publisher={Springer Science and Business Media LLC}, author={Cockett, N.E. and Shay, T.L. and Beever, J.E. and Nielsen, D. and Albretsen, J. and Georges, M. and Peterson, K. and Stephens, A. and Vernon, W. and Timofeevskaia, O. and et al.}, year={1999}, month={Jan}, pages={35–38} }
 @article{nielsen_zaykin_1999, title={Novel tests for marker-disease association using the collaborative study on the genetics of alcoholism data}, volume={17}, ISSN={0741-0395}, url={http://dx.doi.org/10.1002/gepi.1370170745}, DOI={10.1002/gepi.1370170745}, abstractNote={AbstractWe applied several novel tests for association and linkage in the presence of association to the Genetic Analysis Workshop 11 Problem 1 data set. Our analyses included a Hardy‐Weinberg test for association between a marker and a disease susceptibility locus, a Bayesian transmission/disequilibrium test, and a Bayesian case‐control test. Positive results for each of these methods require the presence of population association between the marker and a disease susceptibility locus.}, number={S1}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Nielsen, Dahlia and Zaykin, Dmitri}, year={1999}, pages={S265–S270} }
 @article{nielsen_ehm_weir_1998, title={Detecting Marker-Disease Association by Testing for Hardy-Weinberg Disequilibrium at a Marker Locus}, volume={63}, ISSN={0002-9297}, url={http://dx.doi.org/10.1086/302114}, DOI={10.1086/302114}, abstractNote={We review and extend a recent suggestion that fine-scale localization of a disease-susceptibility locus for a complex disease be done on the basis of deviations from Hardy-Weinberg equilibrium among affected individuals. This deviation is driven by linkage disequilibrium between disease and marker loci in the whole population and requires a heterogeneous genetic basis for the disease. A finding of marker-locus Hardy-Weinberg disequilibrium therefore implies disease heterogeneity and marker-disease linkage disequilibrium. Although a lack of departure of Hardy-Weinberg disequilibrium at marker loci implies that disease susceptibilityweighted linkage disequilibria are zero, given disease heterogeneity, it does not follow that the usual measures of linkage disequilibrium are zero. For disease-susceptibility loci with more than two alleles, therefore, care is needed in the drawing of inferences from marker Hardy-Weinberg disequilibria.}, number={5}, journal={The American Journal of Human Genetics}, publisher={Elsevier BV}, author={Nielsen, Dahlia M. and Ehm, M.G. and Weir, B.S.}, year={1998}, month={Nov}, pages={1531–1540} }
 @article{cockett_jackson_shay_farnir_berghmans_snowder_nielsen_georges_1996, title={Polar Overdominance at the Ovine callipyge Locus}, volume={273}, ISSN={0036-8075 1095-9203}, url={http://dx.doi.org/10.1126/science.273.5272.236}, DOI={10.1126/science.273.5272.236}, abstractNote={
            An inheritable muscular hypertrophy was recently described in sheep and shown to be determined by the
            callipyge
            gene mapped to ovine chromosome 18. Here, the callipyge phenotype was found to be characterized by a nonmendelian inheritance pattern, referred to as polar overdominance, where only heterozygous individuals having inherited the
            callipyge
            mutation from their sire express the phenotype. The possible role of parental imprinting in the determinism of polar overdominance is envisaged.
          }, number={5272}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Cockett, N. E. and Jackson, S. P. and Shay, T. L. and Farnir, F. and Berghmans, S. and Snowder, G. D. and Nielsen, D. M. and Georges, M.}, year={1996}, month={Jul}, pages={236–238} }
 @article{georges_nielsen_mackinnon_mishra_okimoto_pasquino_sargeant_sorensen_steele_zhao_et al._1995, title={Mapping Quantitative Trait Loci Controlling Milk Production in Dairy Cattle by Exploiting Progeny Testing}, volume={139}, DOI={10.1093/genetics/139.2.907}, abstractNote={Abstract
               We have exploited "progeny testing" to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score > or = 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding.}, number={2}, journal={Genetics}, author={Georges, M. and Nielsen, D. and Mackinnon, M. and Mishra, A. and Okimoto, R. and Pasquino, A.T. and Sargeant, L. and Sorensen, A. and Steele, M.R. and Zhao, X. and et al.}, year={1995}, month={Feb}, pages={907–920} }
 @article{cockett_jackson_shay_nielsen_moore_steele_barendse_green_georges_1994, title={Chromosomal localization of the callipyge gene in sheep (Ovis aries) using bovine DNA markers.}, volume={91}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.91.8.3019}, DOI={10.1073/pnas.91.8.3019}, abstractNote={A mutation causing muscular hypertrophy, with associated leanness and improved feed efficiency, has been recently identified in domestic sheep (Ovis aries). Preliminary results indicate that an autosomal dominant gene may be responsible for this economically advantageous trait. We have exploited the conservation in sequence and chromosomal location of DNA markers across Bovidae to map the corresponding callipyge locus to ovine chromosome 18 using a battery of bovine chromosome 21 markers. Chromosomal localization of the ovine callipyge locus is the first step toward positional cloning of the corresponding gene.}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Cockett, N. E. and Jackson, S. P. and Shay, T. L. and Nielsen, D. and Moore, S. S. and Steele, M. R. and Barendse, W. and Green, R. D. and Georges, M.}, year={1994}, month={Apr}, pages={3019–3023} }
 @article{georges_drinkwater_king_mishra_moore_nielsen_sargeant_sorensen_steele_zhao_et al._1993, title={Microsatellite mapping of a gene affecting horn development in Bos taurus}, volume={4}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/ng0693-206}, DOI={10.1038/ng0693-206}, abstractNote={The presence or absence of horns in Bos taurus is thought to be under the genetic control of the autosomal polled locus, characterized by two alleles: P dominant over p, and causing the polled or hornless phenotype. We have demonstrated genetic linkage between the polled locus and two microsatellite markers, GMPOLL-1 and GMPOLL-2, and have assigned the corresponding linkage group to bovine chromosome 1. This confirms the existence of the postulated polled locus and the hypothesized inheritance pattern. It will allow marker assisted selection for the polledness trait in breeding programs and is a first step towards positional cloning and molecular study of a gene that has been subjected to both natural and artificial selection.}, number={2}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Georges, Michel and Drinkwater, Roger and King, Tracey and Mishra, Anuradha and Moore, Stephen S. and Nielsen, Dahlia and Sargeant, Leslie S. and Sorensen, Anita and Steele, Michael R. and Zhao, Xuyun and et al.}, year={1993}, month={Jun}, pages={206–210} }
 @article{georges_dietz_mishra_nielsen_sargeant_sorensen_steele_zhao_leipold_womack_1993, title={Microsatellite mapping of the gene causing weaver disease in cattle will allow the study of an associated quantitative trait locus.}, volume={90}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.90.3.1058}, DOI={10.1073/pnas.90.3.1058}, abstractNote={A genetic disease in cattle, progressive degenerative myeloencephalopathy (weaver disease), is associated with increased milk production. This association could result from population stratification, from a pleiotropic effect of a single gene, or from linkage disequilibrium between the gene causing weaver disease and a quantitative trait locus (QTL) for milk production. To test these hypotheses, we performed an extensive linkage study in a bovine pedigree segregating for the weaver condition and identified a microsatellite locus (TGLA116) closely linked to the weaver gene (zmax, 8.15; theta, 0.03). TGLA116 and, by extension, the weaver locus were assigned to bovine synteny group 13. This microsatellite can be used to identify weaver carriers, to select against this genetic defect, and to study the effect of the corresponding chromosomal region on milk production in Brown Swiss and other breeds of cattle.}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Georges, M. and Dietz, A. B. and Mishra, A. and Nielsen, D. and Sargeant, L. S. and Sorensen, A. and Steele, M. R. and Zhao, X. and Leipold, H. and Womack, J. E.}, year={1993}, month={Feb}, pages={1058–1062} }