@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{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}, journal={BMC Genetics}, author={Salzmann, C. A. and Olivry, T. J. M. and Nielsen, D. M. and Paps, J. S. and Harris, T. L. and Olby, N. J.}, year={2011} }
 @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 Mullerian mimicry in Heliconius erato}, volume={6}, number={4}, journal={PLoS Genetics}, author={Counterman, B. A. and Araujo-Perez, F. and Hines, H. M. and Baxter, S. W. and Morrison, C. M. and Lindstrom, D. P. and Papa, R. and Ferguson, L. and Joron, M. and Ffrench-Constant, R. H. and et al.}, year={2010} }
 @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={Abstract}, 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} }
 @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}, 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.
          }, 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{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={Abstract}, 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} }
 @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_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}, number={Suppl.1}, journal={Genetic Epidemiology}, author={Nielsen, D. and Zaykin, D.}, year={1999}, pages={S265–270} }
 @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} }
 @book{hall_mcelwee_h. w._f. m._nielsen_1987, title={Virginia's forest and wildlife resources: Present and future}, publisher={Blacksburg: School of Forestry and Wildlife Resources, Virginia Polytechnic Institute & State University}, author={Hall, O. F. and McElwee, R. L. Wisdom and H. W., Lamb and F. M., Nielsen and Nielsen, L. A.}, year={1987} }