@article{oloka_da silva pereira_amankwaah_mollinari_pecota_yada_olukolu_zeng_yencho_2021, title={Discovery of a major QTL for root-knot nematode (Meloidogyne incognita) resistance in cultivated sweetpotato (Ipomoea batatas)}, volume={134}, ISSN={0040-5752 1432-2242}, url={http://dx.doi.org/10.1007/s00122-021-03797-z}, DOI={10.1007/s00122-021-03797-z}, abstractNote={Utilizing a high-density integrated genetic linkage map of hexaploid sweetpotato, we discovered a major dominant QTL for root-knot nematode (RKN) resistance and modeled its effects. This discovery is useful for development of a modern sweetpotato breeding program that utilizes marker-assisted selection and genomic selection approaches for faster genetic gain of RKN resistance. The root-knot nematode [Meloidogyne incognita (Kofoid & White) Chitwood] (RKN) causes significant storage root quality reduction and yields losses in cultivated sweetpotato [Ipomoea batatas (L.) Lam.]. In this study, resistance to RKN was examined in a mapping population consisting of 244 progenies derived from a cross (TB) between 'Tanzania,' a predominant African landrace cultivar with resistance to RKN, and 'Beauregard,' an RKN susceptible major cultivar in the USA. We performed quantitative trait loci (QTL) analysis using a random-effect QTL mapping model on the TB genetic map. An RKN bioassay incorporating potted cuttings of each genotype was conducted in the greenhouse and replicated five times over a period of 10 weeks. For each replication, each genotype was inoculated with ca. 20,000 RKN eggs, and root-knot galls were counted ~62 days after inoculation. Resistance to RKN in the progeny was highly skewed toward the resistant parent, exhibiting medium to high levels of resistance. We identified one major QTL on linkage group 7, dominant in nature, which explained 58.3% of the phenotypic variation in RKN counts. This work represents a significant step forward in our understanding of the genetic architecture of RKN resistance and sets the stage for future utilization of genomics-assisted breeding in sweetpotato breeding programs.}, number={7}, journal={Theoretical and Applied Genetics}, publisher={Springer Science and Business Media LLC}, author={Oloka, Bonny Michael and da Silva Pereira, Guilherme and Amankwaah, Victor A. and Mollinari, Marcelo and Pecota, Kenneth V. and Yada, Benard and Olukolu, Bode A. and Zeng, Zhao-Bang and Yencho, G. Craig}, year={2021}, month={Apr}, pages={1945–1955} } @article{da silva pereira_mollinari_qu_thill_zeng_haynes_yencho_2021, title={Quantitative Trait Locus Mapping for Common Scab Resistance in a Tetraploid Potato Full-Sib Population}, volume={105}, ISSN={0191-2917 1943-7692}, url={http://dx.doi.org/10.1094/PDIS-10-20-2270-RE}, DOI={10.1094/PDIS-10-20-2270-RE}, abstractNote={Despite the negative impact of common scab (Streptomyces spp.) on the potato industry, little is known about the genetic architecture of resistance to this bacterial disease in the crop. We evaluated a mapping population (∼150 full sibs) derived from a cross between two tetraploid potatoes ('Atlantic' × B1829-5) in three environments (MN11, PA11, ME12) under natural common scab pressure. Three measures to common scab reaction, namely percentage of scabby tubers and disease area and lesion indices, were found to be highly correlated (>0.76). Because of the large environmental effect, heritability values were zero for all three traits in MN11, but moderate to high in PA11 and ME12 (∼0.44 to 0.79). We identified a single quantitative trait locus (QTL) for lesion index in PA11, ME12, and joint analyses on linkage group 3, explaining ∼22 to 30% of the total variation. The identification of QTL haplotypes and candidate genes contributing to disease resistance can support genomics-assisted breeding approaches in the crop.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.}, number={10}, journal={Plant Disease}, publisher={Scientific Societies}, author={da Silva Pereira, Guilherme and Mollinari, Marcelo and Qu, Xinshun and Thill, Christian and Zeng, Zhao-Bang and Haynes, Kathleen and Yencho, G. Craig}, year={2021}, month={Oct}, pages={3048–3054} } @article{da silva pereira_mollinari_schumann_clough_zeng_yencho_2021, title={The recombination landscape and multiple QTL mapping in a Solanum tuberosum cv. ‘Atlantic’-derived F1 population}, volume={126}, ISSN={0018-067X 1365-2540}, url={http://dx.doi.org/10.1038/s41437-021-00416-x}, DOI={10.1038/s41437-021-00416-x}, abstractNote={There are many challenges involved with the genetic analyses of autopolyploid species, such as the tetraploid potato, Solanum tuberosum (2n = 4x = 48). The development of new analytical methods has made it valuable to re-analyze an F1 population (n = 156) derived from a cross involving 'Atlantic', a widely grown chipping variety in the USA. A fully integrated genetic map with 4285 single nucleotide polymorphisms, spanning 1630 cM, was constructed with MAPpoly software. We observed that bivalent configurations were the most abundant ones (51.0~72.4% depending on parent and linkage group), though multivalent configurations were also observed (2.2~39.2%). Seven traits were evaluated over four years (2006-8 and 2014) and quantitative trait loci (QTL) mapping was carried out using QTLpoly software. Based on a multiple-QTL model approach, we detected 21 QTL for 15 out of 27 trait-year combination phenotypes. A hotspot on linkage group 5 was identified with co-located QTL for maturity, plant yield, specific gravity, and internal heat necrosis resistance evaluated over different years. Additional QTL for specific gravity and dry matter were detected with maturity-corrected phenotypes. Among the genes around QTL peaks, we found those on chromosome 5 that have been previously implicated in maturity (StCDF1) and tuber formation (POTH1). These analyses have the potential to provide insights into the biology and breeding of tetraploid potato and other autopolyploid species.}, number={5}, journal={Heredity}, publisher={Springer Science and Business Media LLC}, author={da Silva Pereira, Guilherme and Mollinari, Marcelo and Schumann, Mitchell J. and Clough, Mark E. and Zeng, Zhao-Bang and Yencho, G. Craig}, year={2021}, month={Mar}, pages={817–830} } @article{zhou_olukolu_gemenet_wu_gruneberg_cao_fei_zeng_george_khan_et al._2020, title={Assembly of whole-chromosome pseudomolecules for polyploid plant genomes using outbred mapping populations}, volume={52}, ISSN={1061-4036 1546-1718}, url={http://dx.doi.org/10.1038/s41588-020-00717-7}, DOI={10.1038/s41588-020-00717-7}, abstractNote={Despite advances in sequencing technologies, assembly of complex plant genomes remains elusive due to polyploidy and high repeat content. Here we report PolyGembler for grouping and ordering contigs into pseudomolecules by genetic linkage analysis. Our approach also provides an accurate method with which to detect and fix assembly errors. Using simulated data, we demonstrate that our approach is of high accuracy and outperforms three existing state-of-the-art genetic mapping tools. Particularly, our approach is more robust to the presence of missing genotype data and genotyping errors. We used our method to construct pseudomolecules for allotetraploid lawn grass utilizing PacBio long reads in combination with restriction site-associated DNA sequencing, and for diploid Ipomoea trifida and autotetraploid potato utilizing contigs assembled from Illumina reads in combination with genotype data generated by single-nucleotide polymorphism arrays and genotyping by sequencing, respectively. We resolved 13 assembly errors for a published I. trifida genome assembly and anchored eight unplaced scaffolds in the published potato genome.}, number={11}, journal={Nature Genetics}, publisher={Springer Science and Business Media LLC}, author={Zhou, Chenxi and Olukolu, Bode and Gemenet, Dorcus C. and Wu, Shan and Gruneberg, Wolfgang and Cao, Minh Duc and Fei, Zhangjun and Zeng, Zhao-Bang and George, Andrew W. and Khan, Awais and et al.}, year={2020}, month={Oct}, pages={1256–1264} } @article{gemenet_lindqvist-kreuze_de boeck_da silva pereira_mollinari_zeng_craig yencho_campos_2020, title={Sequencing depth and genotype quality: accuracy and breeding operation considerations for genomic selection applications in autopolyploid crops}, volume={133}, ISSN={0040-5752 1432-2242}, url={http://dx.doi.org/10.1007/s00122-020-03673-2}, DOI={10.1007/s00122-020-03673-2}, abstractNote={Key messagePolypoid crop breeders can balance resources between density and sequencing depth, dosage information and fewer highly informative SNPs recommended, non-additive models and QTL advantages on prediction dependent on trait architecture.}, number={12}, journal={Theoretical and Applied Genetics}, publisher={Springer Science and Business Media LLC}, author={Gemenet, Dorcus C. and Lindqvist-Kreuze, Hannele and De Boeck, Bert and da Silva Pereira, Guilherme and Mollinari, Marcelo and Zeng, Zhao-Bang and Craig Yencho, G. and Campos, Hugo}, year={2020}, month={Sep}, pages={3345–3363} } @article{lara_santos_jank_chiari_vilela_amadeu_santos_pereira_zeng_garcia_2019, title={Genomic Selection with Allele Dosage in Panicum maximum Jacq.}, volume={9}, ISSN={["2160-1836"]}, DOI={10.1534/g3.118.200986}, abstractNote={Abstract}, number={8}, journal={G3-GENES GENOMES GENETICS}, author={Lara, Leticia A. de C. and Santos, Mateus F. and Jank, Liana and Chiari, Lucimara and Vilela, Mariane de M. and Amadeu, Rodrigo R. and Santos, Jhonathan P. R. and Pereira, Guilherme da S. and Zeng, Zhao-Bang and Garcia, Antonio Augusto F.}, year={2019}, month={Aug}, pages={2463–2475} } @article{lee_yang_chi_turkson_du_kemkemer_zeng_long_zhuang_2017, title={Genetic Architecture of Natural Variation Underlying Adult Foraging Behavior That Is Essential for Survival of Drosophila melanogaster}, volume={9}, ISSN={["1759-6653"]}, DOI={10.1093/gbe/evx089}, abstractNote={Abstract Foraging behavior is critical for the fitness of individuals. However, the genetic basis of variation in foraging behavior and the evolutionary forces underlying such natural variation have rarely been investigated. We developed a systematic approach to assay the variation in survival rate in a foraging environment for adult flies derived from a wild Drosophila melanogaster population. Despite being such an essential trait, there is substantial variation of foraging behavior among D. melanogaster strains. Importantly, we provided the first evaluation of the potential caveats of using inbred Drosophila strains to perform genome-wide association studies on life-history traits, and concluded that inbreeding depression is unlikely a major contributor for the observed large variation in adult foraging behavior. We found that adult foraging behavior has a strong genetic component and, unlike larval foraging behavior, depends on multiple loci. Identified candidate genes are enriched in those with high expression in adult heads and, demonstrated by expression knock down assay, are involved in maintaining normal functions of the nervous system. Our study not only identified candidate genes for foraging behavior that is relevant to individual fitness, but also shed light on the initial stage underlying the evolution of the behavior.}, number={5}, journal={GENOME BIOLOGY AND EVOLUTION}, author={Lee, Yuh Chwen G. and Yang, Qian and Chi, Wanhao and Turkson, Susie A. and Du, Wei A. and Kemkemer, Claus and Zeng, Zhao-Bang and Long, Manyuan and Zhuang, Xiaoxi}, year={2017}, month={May}, pages={1357–1369} } @article{schumann_zeng_clough_yencho_2017, title={Linkage map construction and QTL analysis for internal heat necrosis in autotetraploid potato}, volume={130}, ISSN={0040-5752 1432-2242}, url={http://dx.doi.org/10.1007/s00122-017-2941-1}, DOI={10.1007/s00122-017-2941-1}, abstractNote={A tetraploid potato population was mapped for internal heat necrosis (IHN) using the Infinium ® 8303 potato SNP array, and QTL for IHN were identified on chromosomes 1, 5, 9 and 12 that explained 28.21% of the variation for incidence and 25.3% of the variation for severity. This research represents a significant step forward in our understanding of IHN, and sets the stage for future research focused on testing the utility of these markers in additional breeding populations. Internal heat necrosis (IHN) is a significant non-pathogenic disorder of potato tubers and previous studies have identified AFLP markers linked to IHN susceptibility in the tetraploid, B2721 potato mapping population. B2721 consists of an IHN susceptible×resistant cross: Atlantic×B1829-5. We developed a next-generation SNP-based linkage map of this cross using the Infinium ® 8303 SNP array and conducted additional QTL analyses of IHN susceptibility in the B2721 population. Using SNP dosage sensitive markers, linkage maps for both parents were simultaneously analyzed. The linkage map contained 3427 SNPs and totaled 1397.68 cM. QTL were detected for IHN on chromosomes 1, 5, 9, and 12 using LOD permutation thresholds and colocation of high LOD scores across multiple years. Genetic effects were modeled for each putative QTL. Markers associated with a QTL were regressed in models of effects for IHN incidence and severity for all years. In the full model, the SNP markers were shown to have significant effects for IHN (p < 0.0001), and explained 28.21% of the variation for incidence and 25.3% of the variation for severity. We were able to utilize SNP dosage information to identify and model the effects of putative QTL, and identify SNP loci associated with IHN resistance that need to be confirmed. This research represents a significant step forward in our understanding of IHN, and sets the stage for future research focused on testing the utility of these markers in additional breeding populations.}, number={10}, journal={Theoretical and Applied Genetics}, publisher={Springer Nature}, author={Schumann, Mitchell J. and Zeng, Zhao-Bang and Clough, Mark E. and Yencho, G. Craig}, year={2017}, month={Jun}, pages={2045–2056} } @article{xiong_mckeand_isik_wegrzyn_neale_zeng_da costa e silva_whetten_2016, title={Quantitative trait loci influencing forking defects in an outbred pedigree of loblolly pine}, volume={17}, ISSN={1471-2156}, url={http://dx.doi.org/10.1186/s12863-016-0446-6}, DOI={10.1186/s12863-016-0446-6}, abstractNote={The use of wood as an industrial raw material has led to development of plantation forestry, in which trees are planted, managed, and harvested as crops. The productivity of such plantations often exceeds that of less-intensively-managed forests, and land managers have the option of choosing specific planting stock to produce specific types of wood for industrial use. Stem forking, or division of the stem into two or more stems of roughly equal size, is a character trait important in determining the quality of the stem for production of solid wood products. This trait typically has very low individual-tree heritability, but can be more accurately assessed in clonally-replicated plantings where each genotype is represented by several individual trees. We report results from a quantitative trait mapping experiment in a clonally-replicated full-sibling family of loblolly pine (Pinus taeda L.). Quantitative trait loci influencing forking defects were identified in an outbred full-sibling family of loblolly pine, using single-nucleotide polymorphism markers. Genetic markers in this family segregated either in 1:2:1 (F2 intercross-like segregation) or 1:1 ratio (backcross-like segregation). An integrated linkage map combining markers with different segregation ratios was assembled for this full-sib family, and a total of 409 SNP markers were mapped on 12 linkage groups, covering 1622 cM. Two and three trait loci were identified for forking and ramicorn branch traits, respectively, using the interval mapping method. Three trait loci were detected for both traits using multiple-trait analysis. The detection of three loci for forking and ramicorn branching in a multiple-trait analysis could mean that there are genes with pleiotropic effects on both traits, or that separate genes affecting different traits are clustered together. The detection of genetic loci associated with variation in stem quality traits in this study supports the hypothesis that marker-assisted selection can be used to decrease the rate of stem defects in breeding populations of loblolly pine.}, number={1}, journal={BMC Genetics}, publisher={Springer Science and Business Media LLC}, author={Xiong, Jin S. and McKeand, Steven E. and Isik, Fikret and Wegrzyn, Jill and Neale, David B. and Zeng, Zhao-Bang and da Costa e Silva, Luciano and Whetten, Ross W.}, year={2016}, month={Oct} } @article{laurie_wang_carlini-garcia_zeng_2014, title={Mapping epistatic quantitative trait loci}, volume={15}, ISSN={["1471-2156"]}, DOI={10.1186/s12863-014-0112-9}, abstractNote={How to map quantitative trait loci (QTL) with epistasis efficiently and reliably has been a persistent problem for QTL mapping analysis. There are a number of difficulties for studying epistatic QTL. Linkage can impose a significant challenge for finding epistatic QTL reliably. If multiple QTL are in linkage and have interactions, searching for QTL can become a very delicate issue. A commonly used strategy that performs a two-dimensional genome scan to search for a pair of QTL with epistasis can suffer from low statistical power and also may lead to false identification due to complex linkage disequilibrium and interaction patterns. To tackle the problem of complex interaction of multiple QTL with linkage, we developed a three-stage search strategy. In the first stage, main effect QTL are searched and mapped. In the second stage, epistatic QTL that interact significantly with other identified QTL are searched. In the third stage, new epistatic QTL are searched in pairs. This strategy is based on the consideration that most genetic variance is due to the main effects of QTL. Thus by first mapping those main-effect QTL, the statistical power for the second and third stages of analysis for mapping epistatic QTL can be maximized. The search for main effect QTL is robust and does not bias the search for epistatic QTL due to a genetic property associated with the orthogonal genetic model that the additive and additive by additive variances are independent despite of linkage. The model search criterion is empirically and dynamically evaluated by using a score-statistic based resampling procedure. We demonstrate through simulations that the method has good power and low false positive in the identification of QTL and epistasis. This method provides an effective and powerful solution to map multiple QTL with complex epistatic pattern. The method has been implemented in the user-friendly computer software Windows QTL Cartographer. This will greatly facilitate the application of the method for QTL mapping data analysis.}, journal={BMC GENETICS}, author={Laurie, Cecelia and Wang, Shengchu and Carlini-Garcia, Luciana Aparecida and Zeng, Zhao-Bang}, year={2014}, month={Nov} } @article{huang_zhang_zeng_bushel_2013, title={Improved Sparse Multi-Class SVM and Its Application for Gene Selection in Cancer Classification}, volume={12}, ISSN={1176-9351 1176-9351}, url={http://dx.doi.org/10.4137/cin.s10212}, DOI={10.4137/cin.s10212}, abstractNote={Background Microarray techniques provide promising tools for cancer diagnosis using gene expression profiles. However, molecular diagnosis based on high-throughput platforms presents great challenges due to the overwhelming number of variables versus the small sample size and the complex nature of multi-type tumors. Support vector machines (SVMs) have shown superior performance in cancer classification due to their ability to handle high dimensional low sample size data. The multi-class SVM algorithm of Crammer and Singer provides a natural framework for multi-class learning. Despite its effective performance, the procedure utilizes all variables without selection. In this paper, we propose to improve the procedure by imposing shrinkage penalties in learning to enforce solution sparsity. }, journal={Cancer Informatics}, publisher={SAGE Publications}, author={Huang, Lingkang and Zhang, Hao Helen and Zeng, Zhao-Bang and Bushel, Pierre R.}, year={2013}, month={Jan}, pages={CIN.S10212} } @article{kaddurah-daouk_yuan_boyle_matson_wang_zeng_zhu_dougherty_yao_chen_et al._2012, title={Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile}, volume={2}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep00667}, DOI={10.1038/srep00667}, abstractNote={Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Kaddurah-Daouk, Rima and Yuan, Peixiong and Boyle, Stephen H. and Matson, Wayne and Wang, Zhi and Zeng, Zhao Bang and Zhu, Hongjie and Dougherty, George G. and Yao, Jeffrey K. and Chen, Guang and et al.}, year={2012}, month={Sep} } @inbook{silva_wang_zeng_2012, title={Composite Interval Mapping and Multiple Interval Mapping: Procedures and Guidelines for Using Windows QTL Cartographer}, ISBN={9781617797842 9781617797859}, ISSN={1064-3745 1940-6029}, url={http://dx.doi.org/10.1007/978-1-61779-785-9_6}, DOI={10.1007/978-1-61779-785-9_6}, abstractNote={Tremendous progress has been made in recent years on developing statistical methods for mapping quantitative trait loci (QTL) from crosses of inbred lines. In this chapter, we provide an introduction of composite interval mapping and multiple interval mapping methods for mapping QTL from inbred line crosses and also detailed instructions to perform the analyses in Windows QTL Cartographer. For each method, we discuss the meaning of each option in the analysis procedures and how to understand and interpret the mapping results through a work-out example.}, booktitle={Methods in Molecular Biology}, publisher={Humana Press}, author={Silva, Luciano Da Costa E. and Wang, Shengchu and Zeng, Zhao-Bang}, year={2012}, pages={75–119} } @article{abo_hebbring_ji_zhu_zeng_batzler_jenkins_biernacka_snyder_drews_et al._2012, title={Merging pharmacometabolomics with pharmacogenomics using ‘1000 Genomes’ single-nucleotide polymorphism imputation}, volume={22}, ISSN={1744-6872}, url={http://dx.doi.org/10.1097/FPC.0b013e32835001c9}, DOI={10.1097/fpc.0b013e32835001c9}, abstractNote={Objective We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by single-nucleotide polymorphism (SNP) imputation of metabolomic-derived pathway data on a ‘scaffolding’ of genome-wide association (GWAS) SNP data to broaden and accelerate ‘pharmacometabolomics-informed pharmacogenomic’ studies by eliminating the need for initial genotyping and by making broader SNP association testing possible. Methods We previously genotyped 131 tag SNPs for six genes encoding enzymes in the glycine synthesis and degradation pathway using DNA from 529 depressed patients treated with citalopram/escitalopram to pursue a glycine metabolomics ‘signal’ associated with selective serotonine reuptake inhibitor response. We identified a significant SNP in the glycine dehydrogenase gene. Subsequently, GWAS SNP data were generated for the same patients. In this study, we compared SNP imputation within 200 kb of these same six genes with the results of the previous tag SNP strategy as a rapid strategy for merging pharmacometabolomic and pharmacogenomic data. Results Imputed genotype data provided greater coverage and higher resolution than did tag SNP genotyping, with a higher average genotype concordance between genotyped and imputed SNP data for ‘1000 Genomes’ (96.4%) than HapMap 2 (93.2%) imputation. Many low P-value SNPs with novel locations within genes were observed for imputed compared with tag SNPs, thus altering the focus for subsequent functional genomic studies. Conclusion These results indicate that the use of GWAS data to impute SNPs for genes in pathways identified by other ‘omics’ approaches makes it possible to rapidly and cost efficiently identify SNP markers to ‘broaden’ and accelerate pharmacogenomic studies.}, number={4}, journal={Pharmacogenetics and Genomics}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Abo, Ryan and Hebbring, Scott and Ji, Yuan and Zhu, Hongjie and Zeng, Zhao-Bang and Batzler, Anthony and Jenkins, Gregory D. and Biernacka, Joanna and Snyder, Karen and Drews, Maureen and et al.}, year={2012}, month={Apr}, pages={247–253} } @article{trupp_zhu_wikoff_baillie_zeng_karp_fiehn_krauss_kaddurah-daouk_2012, title={Metabolomics Reveals Amino Acids Contribute to Variation in Response to Simvastatin Treatment}, volume={7}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0038386}, DOI={10.1371/journal.pone.0038386}, abstractNote={Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolomics platform to evaluate global effects of simvastatin on intermediary metabolism. Analyses were conducted in 148 participants in the Cholesterol and Pharmacogenetics study who were profiled pre and six weeks post treatment with 40 mg/day simvastatin: 100 randomly selected from the full range of the LDL-C response distribution and 24 each from the top and bottom 10% of this distribution (“good” and “poor” responders, respectively). The metabolic signature of drug exposure in the full range of responders included essential amino acids, lauric acid (p<0.0055, q<0.055), and alpha-tocopherol (p<0.0003, q<0.017). Using the HumanCyc database and pathway enrichment analysis, we observed that the metabolites of drug exposure were enriched for the pathway class amino acid degradation (p<0.0032). Metabolites whose change correlated with LDL-C lowering response to simvastatin in the full range responders included cystine, urea cycle intermediates, and the dibasic amino acids ornithine, citrulline and lysine. These dibasic amino acids share plasma membrane transporters with arginine, the rate-limiting substrate for nitric oxide synthase (NOS), a critical mediator of cardiovascular health. Baseline metabolic profiles of the good and poor responders were analyzed by orthogonal partial least square discriminant analysis so as to determine the metabolites that best separated the two response groups and could be predictive of LDL-C response. Among these were xanthine, 2-hydroxyvaleric acid, succinic acid, stearic acid, and fructose. Together, the findings from this study indicate that clusters of metabolites involved in multiple pathways not directly connected with cholesterol metabolism may play a role in modulating the response to simvastatin treatment. Trial Registration ClinicalTrials.gov NCT00451828}, number={7}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Trupp, Miles and Zhu, Hongjie and Wikoff, William R. and Baillie, Rebecca A. and Zeng, Zhao-Bang and Karp, Peter D. and Fiehn, Oliver and Krauss, Ronald M. and Kaddurah-Daouk, Rima}, editor={Oresic, MatejEditor}, year={2012}, month={Jul}, pages={e38386} } @article{silva_wang_zeng_2012, title={Multiple trait multiple interval mapping of quantitative trait loci from inbred line crosses}, volume={13}, journal={BMC Genetics}, author={Silva, L. D. E. and Wang, S. C. and Zeng, Z. B.}, year={2012} } @article{kaddurah-daouk_baillie_zhu_zeng_wiest_nguyen_wojnoonski_watkins_trupp_krauss_2011, title={Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment}, volume={6}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0025482}, abstractNote={Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy.}, number={10}, journal={PLOS ONE}, author={Kaddurah-Daouk, Rima and Baillie, Rebecca A. and Zhu, Hongjie and Zeng, Zhao-Bang and Wiest, Michelle M. and Nguyen, Uyen Thao and Wojnoonski, Katie and Watkins, Steven M. and Trupp, Miles and Krauss, Ronald M.}, year={2011}, month={Oct} } @article{duarte_zeng_2011, title={High-Confidence Discovery of Genetic Network Regulators in Expression Quantitative Trait Loci Data}, volume={187}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.110.124685}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Duarte, Christine W. and Zeng, Zhao-Bang}, year={2011}, month={Mar}, pages={955–964} } @article{chakraborty_zeng_2011, title={QTL Mapping for Days to Flowering under Drought Condition in Rice (Oryza sativa L.) Genome}, volume={39}, ISSN={1842-4309 0255-965X}, url={http://dx.doi.org/10.15835/nbha3915610}, DOI={10.15835/nbha3915610}, abstractNote={QTL for days to flowering in rice under drought condition were mapped using a DH population derived from a cross between a deep-rooted upland adapted japonica genotype CT9993-5-10-1-M and a lowland adapted shallow-rooted moderately drought tolerant indica genotype IR62266-42-6-2. QTL mapping was performed following three different mapping models viz. simple (SIM), composite (CIM) and multiple mapping model (MIM) using WinQTL Cartographer version 2.5.006. SIM located 12 QTL for days to flowering spread over nine chromosomes whereas CIM and MIM each located 5 QTL with a threshold LOD score of 2.5. A comparison of the QTL detected by three different models identified five QTL that were common across at least two models for days to flowering. In MIM analysis, the detected QTL (qHD-1-b) between flanking markers (RG109 – ME1014) located on chromosome 1 recorded positive effect (1.4090) but the remaining four QTL had negative effect. The QTL (qHD-3-a) detected between flanking markers (RG104 – RG409) by both MIM and SIM in the present study was also reported earlier as linked with the marker RG104. The five common QTL detected by at least two models could be considered as stable QTL for days to flowering under drought and might be of practical use in marker assisted selection.}, number={1}, journal={Notulae Botanicae Horti Agrobotanici Cluj-Napoca}, publisher={AcademicPres (EAP) Publishing House}, author={Chakraborty, Supriyo and Zeng, Zhao Bang}, year={2011}, month={May}, pages={58} } @article{silva_zeng_2010, title={Current Progress on Statistical Methods for Mapping Quantitative Trait Loci from Inbred Line Crosses}, volume={20}, ISSN={["1520-5711"]}, DOI={10.1080/10543400903572845}, abstractNote={Tremendous progress has been made in recent years on developing statistical methods for mapping quantitative trait loci (QTL) from crosses of inbred lines. Most of the recent research is focused on strategies for mapping multiple-QTL and associated model selection procedures and criterion. We review the progress of research in this area on one trait and multiple traits by maximum likelihood and Bayesian methods.}, number={2}, journal={JOURNAL OF BIOPHARMACEUTICAL STATISTICS}, author={Silva, Luciano Da Costa E. and Zeng, Zhao-Bang}, year={2010}, pages={454–481} } @article{ji_hebbring_zhu_jenkins_biernacka_snyder_drews_fiehn_zeng_schaid_et al._2010, title={Glycine and a Glycine Dehydrogenase (GLDC) SNP as Citalopram/Escitalopram Response Biomarkers in Depression: Pharmacometabolomics-Informed Pharmacogenomics}, volume={89}, ISSN={0009-9236 1532-6535}, url={http://dx.doi.org/10.1038/clpt.2010.250}, DOI={10.1038/clpt.2010.250}, abstractNote={Major depressive disorder (MDD) is a common psychiatric disease. Selective serotonin reuptake inhibitors (SSRIs) are an important class of drugs used in the treatment of MDD. However, many patients do not respond adequately to SSRI therapy. We used a pharmacometabolomics-informed pharmacogenomic research strategy to identify citalopram/escitalopram treatment outcome biomarkers. Metabolomic assay of plasma samples from 20 escitalopram remitters and 20 nonremitters showed that glycine was negatively associated with treatment outcome (P = 0.0054). This observation was pursued by genotyping tag single-nucleotide polymorphisms (SNPs) for genes encoding glycine synthesis and degradation enzymes, using 529 DNA samples from SSRI-treated MDD patients. The rs10975641 SNP in the glycine dehydrogenase (GLDC) gene was associated with treatment outcome phenotypes. Genotyping for rs10975641 was carried out in 1,245 MDD patients in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and its presence was significant (P = 0.02) in DNA taken from these patients. These results highlight a possible role for glycine in SSRI response and illustrate the use of pharmacometabolomics to “inform” pharmacogenomics. Clinical Pharmacology & Therapeutics (2011) 89 1, 97–104. doi: 10.1038/clpt.2010.250}, number={1}, journal={Clinical Pharmacology & Therapeutics}, publisher={Springer Nature}, author={Ji, Y and Hebbring, S and Zhu, H and Jenkins, G D and Biernacka, J and Snyder, K and Drews, M and Fiehn, O and Zeng, Z and Schaid, D and et al.}, year={2010}, month={Nov}, pages={97–104} } @article{kaddurah-daouk_baillie_zhu_zeng_wiest_nguyen_watkins_krauss_2010, title={Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study}, volume={6}, ISSN={1573-3882 1573-3890}, url={http://dx.doi.org/10.1007/s11306-010-0207-x}, DOI={10.1007/s11306-010-0207-x}, abstractNote={Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0207-x) contains supplementary material, which is available to authorized users.}, number={2}, journal={Metabolomics}, publisher={Springer Nature}, author={Kaddurah-Daouk, Rima and Baillie, Rebecca A. and Zhu, Hongjie and Zeng, Zhao-Bang and Wiest, Michelle M. and Nguyen, Uyen Thao and Watkins, Steven M. and Krauss, Ronald M.}, year={2010}, month={Apr}, pages={191–201} } @book{e silva_chang_zeng_2010, title={Power, sample size and confidence interval for quantitative trait loci mapping on multiple traits}, author={E Silva, L.D.C. and Chang, S.-M. and Zeng, Z.-B.}, year={2010} } @article{hu_liu_zeng_ding_yin_gong_zhang_2010, title={QTL Identification Using Combined Linkage and Linkage Disequilibrium Mapping for Milk Production Traits on BTA6 in Chinese Holstein Population}, volume={23}, ISSN={["1976-5517"]}, DOI={10.5713/ajas.2010.10011}, abstractNote={Milk production traits are important economic traits for dairy cattle. The aim of the present study was to refine the position of previously detected quantitative trait loci (QTL) on bovine chromosome 6 affecting milk production traits in Chinese Holstein dairy cattle. A daughter design with 918 daughters from 8 elite sire families and 14 markers spanning the previously identified QTL region were used in the analysis. We employed a combined linkage and linkage disequilibrium analysis (LDLA) approach with two options for calculating the IBD probabilities, one was based on haplotypes of all 14 markers (named Method 1) and the other based on haplotypes with sliding windows of 5 markers (named Method 2). For milk fat yield, the two methods revealed a highly significant QTL located within a 6.5 cM interval (Method 1) and a 4.0 cM interval (Method 2), respectively. For milk protein yield, a highly significant QTL was detected within a 3.0 cM interval (Method 1) or a 2.5 cM interval (Method 2). These results confirmed the findings of our previous study and other studies, and greatly narrowed down the QTL positions.}, number={10}, journal={ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES}, author={Hu, F. and Liu, J. F. and Zeng, Z. B. and Ding, X. D. and Yin, C. C. and Gong, Y. Z. and Zhang, Q.}, year={2010}, month={Oct}, pages={1261–1267} } @article{wang_jacob_ghosh_wang_zeng_2009, title={A Joint Association Test for Multiple SNPs in Genetic Case-Control Studies}, volume={33}, ISSN={["0741-0395"]}, DOI={10.1002/gepi.20368}, abstractNote={Abstract}, number={2}, journal={GENETIC EPIDEMIOLOGY}, author={Wang, Tao and Jacob, Howard and Ghosh, Soumitra and Wang, Xujing and Zeng, Zhao-Bang}, year={2009}, month={Feb}, pages={151–163} } @article{wang_zeng_2009, title={Contribution of genetic effects to genetic variance components with epistasis and linkage disequilibrium}, volume={10}, ISSN={["1471-2156"]}, DOI={10.1186/1471-2156-10-52}, abstractNote={Cockerham genetic models are commonly used in quantitative trait loci (QTL) analysis with a special feature of partitioning genotypic variances into various genetic variance components, while the F(infinity) genetic models are widely used in genetic association studies. Over years, there have been some confusion about the relationship between these two type of models. A link between the additive, dominance and epistatic effects in an F(infinity) model and the additive, dominance and epistatic variance components in a Cockerham model has not been well established, especially when there are multiple QTL in presence of epistasis and linkage disequilibrium (LD).In this paper, we further explore the differences and links between the F(infinity) and Cockerham models. First, we show that the Cockerham type models are allelic based models with a special modification to correct a confounding problem. Several important moment functions, which are useful for partition of variance components in Cockerham models, are also derived. Next, we discuss properties of the Finfinity models in partition of genotypic variances. Its difference from that of the Cockerham models is addressed. Finally, for a two-locus biallelic QTL model with epistasis and LD between the loci, we present detailed formulas for calculation of the genetic variance components in terms of the additive, dominant and epistatic effects in an F(infinity) model. A new way of linking the Cockerham and F(infinity) model parameters through their coding variables of genotypes is also proposed, which is especially useful when reduced F(infinity) models are applied.The Cockerham type models are allele-based models with a focus on partition of genotypic variances into various genetic variance components, which are contributed by allelic effects and their interactions. By contrast, the F(infinity) regression models are genotype-based models focusing on modeling and testing of within-locus genotypic effects and locus-by-locus genotypic interactions. When there is no need to distinguish the paternal and maternal allelic effects, these two types of models are transferable. Transformation between an F(infinity) model's parameters and its corresponding Cockerham model's parameters can be established through a relationship between their coding variables of genotypes. Genetic variance components in terms of the additive, dominance and epistatic genetic effects in an F(infinity) model can then be calculated by translating formulas derived for the Cockerham models.}, journal={BMC GENETICS}, author={Wang, Tao and Zeng, Zhao-Bang}, year={2009}, month={Sep} } @article{kim_feng_zeng_2009, title={Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains}, volume={33}, ISSN={0741-0395 1098-2272}, url={http://dx.doi.org/10.1002/gepi.20349}, DOI={10.1002/gepi.20349}, abstractNote={Measuring and Partitioning the High-Order Linkage Disequilibrium by Multiple Order Markov Chains Yunjung Kim,1,2y Sheng Feng,1,2y and Zhao-Bang Zeng Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina Department of Statistics, North Carolina State University, Raleigh, North Carolina Department of Genetics, North Carolina State University, Raleigh, North Carolina}, number={2}, journal={Genetic Epidemiology}, publisher={Wiley}, author={Kim, Yunjung and Feng, Sheng and Zeng, Zhao-Bang}, year={2009}, month={Feb}, pages={181–181} } @article{kim_feng_zeng_2009, title={Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains (vol 32, pg 301, 2008)}, volume={33}, number={2}, journal={Genetic Epidemiology}, author={Kim, Y. J. and Feng, S. and Zeng, Z. B.}, year={2009}, pages={181–181} } @article{zou_zeng_2009, title={Multiple interval mapping for gene expression QTL analysis}, volume={137}, ISSN={["1573-6857"]}, DOI={10.1007/s10709-009-9365-z}, abstractNote={To find the correlations between genome-wide gene expression variations and sequence polymorphisms in inbred cross populations, we developed a statistical method to claim expression quantitative trait loci (eQTL) in a genome. The method is based on multiple interval mapping (MIM), a model selection procedure, and uses false discovery rate (FDR) to measure the statistical significance of the large number of eQTL. We compared our method with a similar procedure proposed by Storey et al. and found that our method can be more powerful. We identified the features in the two methods that resulted in different statistical powers for eQTL detection, and confirmed them by simulation. We organized our computational procedure in an R package which can estimate FDR for positive findings from similar model selection procedures. The R package, MIM-eQTL, can be found at http://www.statgen.ncsu.edu/~wzou/MIM.eQTL.html .}, number={2}, journal={GENETICA}, author={Zou, Wei and Zeng, Zhao-Bang}, year={2009}, month={Nov}, pages={125–134} } @article{weir_hill_zhu_zeng_2009, title={The Third International Conference of Quantitative Genetics}, volume={136}, ISSN={["1573-6857"]}, DOI={10.1007/s10709-008-9315-1}, abstractNote={The third International Conference of Quantitative Genetics was held at Zheijiang University, Hangzhou, China from August 18 to 24, 2007. The papers of invited speakers at the conference comprise this issue of Genetica. The first ICQG was held in Ames, Iowa in 1976 and the second in Raleigh, North Carolina in 1987. Since the conference in Raleigh statistical techniques then in their infancy, such as QTL mapping and MCMC analysis, have become standard but still developing practices. New molecular techniques have enabled individual genes contributing to variation in quantitative traits to be identified. The new technologies of genomics and gene expression arrays provide new opportunities to understand the genetic basis of quantitative characters, but also new problems in statistical inference. The application of quantitative genetics has broadened from primarily animal and plant breeding into the genetics of human disease and the analyses of natural populations and their evolution. Indeed, it is now often termed the genetics of complex traits, in recognition of the fact that most diseases, for example, are not determined by just one or a handful of genes. The death of quantitative genetics has been forecast for 40 years or more; but it lives on, strongly. The wide range of topics and methods discussed in these papers show the diversity of applications of quantitative genetics and of the technologies employed. The conference was run as a single session in order to foster interactions and exchange of ideas and problems among those working on these different systems, species and technologies. In addition a number of selected short papers were presented in the oral sessions and others as posters. There were a total of 201 delegates at the conference, including 129 from outside the home country, who had opportunity to see and hear about research in quantitative genetics in China. Zhejiang University is one of the five most highly ranked research institutions in China, and arose from the merger of four specialist universities in the city. A new campus is being built and part of the University is already on that site. The City of Hangzhou is one of the seven ancient capital cities of China, and has many attractive features, including the famed West Lake. It is the capital city of Zheijiang province and has a population of nearly 4 million. Participants in Hangzhou considered intervals of 10 or 20 years far too long to enable adequate discussion and review of a changing subject, and that 5 years should be aimed for. Accordingly, the fourth conference will be held in Edinburgh in 2012. Those from outside the University are grateful to Jun Zhu and to the large team of staff and students at Zheijiang University led by Longjian Fan who undertook all the work and were exposed to the stresses and strains of managing a successful large conference. The conference and social events were excellent and provided many visitors their first exposure to Chinese culture. We are also grateful to Ron B. S. Weir Department of Biostatistics, University of Washington, Seattle, WA 98915, USA}, number={2}, journal={GENETICA}, author={Weir, Bruce S. and Hill, William G. and Zhu, Jun and Zeng, Zhao-Bang}, year={2009}, month={Jun}, pages={211–212} } @article{aylor_zeng_2008, title={From classical genetics to quantitative genetics to systems biology: Modeling epistasis}, volume={4}, number={3}, journal={PLoS Genetics}, author={Aylor, D. L. and Zeng, Z. B.}, year={2008} } @article{huang_heinloth_zeng_paules_bushel_2008, title={Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants}, volume={9}, journal={BMC Genomics}, author={Huang, L. and Heinloth, A. N. and Zeng, Z. B. and Paules, R. S. and Bushel, P. R.}, year={2008} } @article{kim_feng_zeng_2008, title={Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains}, volume={32}, ISSN={["1098-2272"]}, DOI={10.1002/gepi.20305}, abstractNote={Abstract}, number={4}, journal={GENETIC EPIDEMIOLOGY}, author={Kim, Yunjung and Feng, Sheng and Zeng, Zhao-Bang}, year={2008}, month={May}, pages={301–312} } @article{franco garcia_wang_melchinger_zeng_2008, title={Quantitative Trait Loci Mapping and The Genetic Basis of Heterosis in Maize and Rice}, volume={180}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.107.082867}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Franco Garcia, Antonio Augusto and Wang, Shengchu and Melchinger, Albrecht E. and Zeng, Zhao-Bang}, year={2008}, month={Nov}, pages={1707–1724} } @article{zou_zeng_2008, title={Statistical Methods for Mapping Multiple QTL}, volume={2008}, ISSN={1687-5370 1687-5389}, url={http://dx.doi.org/10.1155/2008/286561}, DOI={10.1155/2008/286561}, abstractNote={Since Lander and Botstein proposed the interval mapping method for QTL mapping data analysis in 1989, tremendous progress has been made in the last many years to advance new and powerful statistical methods for QTL analysis. Recent research progress has been focused on statistical methods and issues for mapping multiple QTL together. In this article, we review this progress. We focus the discussion on the statistical methods for mapping multiple QTL by maximum likelihood and Bayesian methods and also on determining appropriate thresholds for the analysis.}, journal={International Journal of Plant Genomics}, publisher={Hindawi Limited}, author={Zou, Wei and Zeng, Zhao-Bang}, year={2008}, pages={1–8} } @article{yang_gao_wang_zhang_zeng_wu_2007, title={A semiparametric approach for composite functional mapping of dynamic quantitative traits}, volume={177}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.107.077321}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Yang, Runqing and Gao, Huijiang and Wang, Xin and Zhang, Ji and Zeng, Zhao-Bang and Wu, Rongling}, year={2007}, month={Nov}, pages={1859–1870} } @article{lai_leips_zou_roberts_wollenberg_parnell_zeng_ordovas_mackay_2007, title={Speed-mapping quantitative trait loci using microarrays}, volume={4}, ISSN={["1548-7105"]}, DOI={10.1038/NMETH1084}, abstractNote={We developed a rapid, economical method for high-resolution quantitative trait locus (QTL) mapping using microarrays for selective genotyping of pooled DNA samples. We generated 21,207 F2 flies from two inbred Drosophila melanogaster strains with known QTLs affecting lifespan, and hybridized DNA pools of young and old flies to microarrays. We used changes of gene frequency of 2,326 single-feature polymorphisms (SFPs) to map previously identified and additional QTLs affecting lifespan.}, number={10}, journal={NATURE METHODS}, author={Lai, Chao-Qiang and Leips, Jeff and Zou, Wei and Roberts, Jessica F. and Wollenberg, Kurt R. and Parnell, Laurence D. and Zeng, Zhao-Bang and Ordovas, Jose M. and Mackay, Trudy F. C.}, year={2007}, month={Oct}, pages={839–841} } @article{zeng_2007, title={The Hill–Robertson effect is a consequence of interplay between linkage, selection and drift: a commentary on ‘The effect of linkage on limits to artificial selection’ by W. G. Hill and A. Robertson}, volume={89}, ISSN={0016-6723 1469-5073}, url={http://dx.doi.org/10.1017/s0016672308009506}, DOI={10.1017/s0016672308009506}, abstractNote={The Hill–Robertson effect is a consequence of interplay between linkage, selection and drift: a commentary on ‘The effect of linkage on limits to artificial selection’ by W. G. Hill and A. Robertson - Volume 89 Issue 5-6}, number={5-6}, journal={Genetics Research}, publisher={Cambridge University Press (CUP)}, author={Zeng, Zhao Bang}, year={2007}, month={Dec}, pages={309–310} } @article{melchinger_utz_piepho_zeng_schoen_2007, title={The role of epistasis in the manifestation of heterosis: A systems-oriented approach}, volume={177}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.107.077537}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Melchinger, A. E. and Utz, H. F. and Piepho, H. -P. and Zeng, Z. -B. and Schoen, C. C.}, year={2007}, month={Nov}, pages={1815–1825} } @article{zou_aylor_zeng_2007, title={eQTL Viewer: visualizing how sequence variation affects genome-wide transcription}, volume={8}, number={7}, journal={BMC Bioinformatics}, author={Zou, W. and Aylor, D. L. and Zeng, Z. B.}, year={2007} } @article{wang_weir_zeng_2006, title={A population-based latent variable approach for association mapping of quantitative trait loci}, volume={70}, ISSN={["0003-4800"]}, DOI={10.1111/j.1469-1809.2006.00264.x}, abstractNote={Summary}, journal={ANNALS OF HUMAN GENETICS}, author={Wang, T and Weir, B and Zeng, ZB}, year={2006}, month={Jul}, pages={506–523} } @article{wang_zeng_2006, title={Models and partition of variance for quantitative trait loci with epistasis and linkage disequilibrium}, volume={7}, journal={BMC Genetics}, author={Wang, T. and Zeng, Z. B.}, year={2006} } @article{li_wang_zeng_2006, title={Multiple-interval mapping for ordinal traits}, volume={173}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.105.054619}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Li, Jian and Wang, Shengchu and Zeng, Zhao-Bang}, year={2006}, month={Jul}, pages={1649–1663} } @article{chen_griffey_maroof_stromberg_biyashev_zhao_chappell_pridgen_dong_zeng_2006, title={Validation of two major quantitative trait loci for fusarium head blight resistance in Chinese wheat line W14}, volume={125}, ISSN={["1439-0523"]}, DOI={10.1111/j.1439-0523.2006.01182.x}, abstractNote={Abstract}, number={1}, journal={PLANT BREEDING}, author={Chen, J and Griffey, CA and Maroof, MAS and Stromberg, EL and Biyashev, RM and Zhao, W and Chappell, MR and Pridgen, TH and Dong, Y and Zeng, Z}, year={2006}, month={Feb}, pages={99–101} } @article{kirst_basten_myburg_zeng_sederoff_2005, title={Genetic architecture of transcript-level variation in differentiating xylem of a eucalyptus hybrid}, volume={169}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.039198}, abstractNote={Abstract}, number={4}, journal={GENETICS}, author={Kirst, M and Basten, CJ and Myburg, AA and Zeng, ZB and Sederoff, RR}, year={2005}, month={Apr}, pages={2295–2303} } @article{liu_zeng_2005, title={Mixture model equations for marker-assisted genetic evaluation}, volume={122}, ISSN={["1439-0388"]}, DOI={10.1111/j.1439-0388.2005.00525.x}, abstractNote={Summary}, number={4}, journal={JOURNAL OF ANIMAL BREEDING AND GENETICS}, author={Liu, Y and Zeng, ZB}, year={2005}, month={Aug}, pages={229–239} } @article{zeng_wang_zou_2005, title={Modeling quantitative trait loci and interpretation of models}, volume={169}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.104.035857}, abstractNote={Abstract}, number={3}, journal={GENETICS}, author={Zeng, ZB and Wang, T and Zou, W}, year={2005}, month={Mar}, pages={1711–1725} } @article{zeng_2005, title={QTL mapping and the genetic basis of adaptation: recent developments}, volume={123}, ISSN={["1573-6857"]}, DOI={10.1007/s10709-004-2705-0}, abstractNote={Quantitative trait loci (QTL) mapping has been used in a number of evolutionary studies to study the genetic basis of adaptation by mapping individual QTL that explain the differences between differentiated populations and also estimating their effects and interaction in the mapping population. This analysis can provide clues about the evolutionary history of populations and causes of the population differentiation. QTL mapping analysis methods and associated computer programs provide us tools for such an inference on the genetic basis and architecture of quantitative trait variation in a mapping population. Current methods have the capability to separate and localize multiple QTL and estimate their effects and interaction on a quantitative trait. More recent methods have been targeted to provide a comprehensive inference on the overall genetic architecture of multiple traits in a number of environments. This development is important for evolutionary studies on the genetic basis of multiple trait variation, genotype by environment interaction, host-parasite interaction, and also microarray gene expression QTL analysis.}, number={1-2}, journal={GENETICA}, author={Zeng, ZB}, year={2005}, month={Feb}, pages={25–37} } @article{tao_zeng_li_hartl_laurie_2003, title={Genetic dissection of hybrid Incompatibilities between Drosophila simulansand D. mauritiana. II. Mapping hybrid male sterility loci on the third chromosome}, volume={164}, number={4}, journal={Genetics}, author={Tao, Y. and Zeng, Z. B. and Li, J. and Hartl, D. L. and Laurie, C. C.}, year={2003}, pages={1399–1418} } @inbook{zeng_2003, place={New York}, title={Quantitative Trait Loci Mapping}, ISBN={9780333803868}, booktitle={Nature encyclopedia of the human genome}, publisher={Nature Publishing Group}, author={Zeng, Z.-B.}, editor={Cooper, DavidEditor}, year={2003} } @article{balding_carothers_marchini_cardon_vetta_griffiths_weir_hill_goldstein_strimmer_et al._2002, title={Discussion on the meeting on 'Statistical modelling and analysis of genetic data'}, volume={64}, ISSN={1369-7412 1467-9868}, url={http://dx.doi.org/10.1111/1467-9868.00359}, DOI={10.1111/1467-9868.00359}, abstractNote={David J. Balding .Imperial College School of Medicine, London/ I extendmy apologies to the authors that an unavoidable commitment arising unexpectedly in the 18 hours before the meeting robbed me of my final preparation, so that my comments at the meeting were poorly presented. I shall try to do a better job in this written version, and to leave enough space I shall omit my introductory comments about the role of statisticians in bioinformatics.}, number={4}, journal={Journal of the Royal Statistical Society: Series B (Statistical Methodology)}, publisher={Wiley}, author={Balding, D.J. and Carothers, A.D. and Marchini, J.L. and Cardon, L.R. and Vetta, A. and Griffiths, B. and Weir, B.S. and Hill, W.G. and Goldstein, D. and Strimmer, K. and et al.}, year={2002}, month={Oct}, pages={737–775} } @article{wu_ma_wu_zeng_2002, title={Linkage mapping of sex-specific differences}, volume={79}, ISSN={["0016-6723"]}, DOI={10.1017/s0016672301005389}, abstractNote={Most current linkage analyses assume identical fractions of meiotic recombination between homologous marker loci of the two sexes. This assumption is not realistic, because considerable sex-related differences have been observed in recombination fraction. In this paper, a general EM-based algorithm is presented to estimate sex-specific recombination fractions for a mixed set of molecular markers segregating differently in a full-sib family derived from two heterozygous parents. The asymptotic variances of the estimates of linkage specifically for each of the parents are evaluated using a numerical analysis based on information functions. This approach will have important implications for precise gene mapping based on sex-specific linkage maps.}, number={1}, journal={GENETICAL RESEARCH}, author={Wu, RL and Ma, CX and Wu, SS and Zeng, ZB}, year={2002}, month={Feb}, pages={85–96} } @article{kao_zeng_2002, title={Modeling epistasis of quantitative trait loci using Cockerham's model}, volume={160}, number={3}, journal={Genetics}, author={Kao, C. H. and Zeng, Z. B.}, year={2002}, pages={1243–1261} } @article{wu_ma_painter_zeng_2002, title={Simultaneous maximum likelihood estimation of linkage and linkage phases in outcrossing species}, volume={61}, ISSN={["1096-0325"]}, DOI={10.1006/tpbi.2002.1577}, abstractNote={With the advent of new molecular marker technologies, it is now feasible to initiate genome projects for outcrossing plant species, which have not received much attention in genetic research, despite their great agricultural and environmental value. Because outcrossing species typically have heterogeneous genomes, data structure for molecular markers representing an entire genome is complex: some markers may have more alleles than others, some markers are codominant whereas others are dominant, and some markers are heterozygous in one parent but fixed in the other parent whereas the opposite can be true for other markers. A major difficulty in analyzing these different types of marker at the same time arises from uncertainty about parental linkage phases over markers. In this paper, we present a general maximum-likelihood-based algorithm for simultaneously estimating linkage and linkage phases for a mixed set of different marker types containing fully informative markers (segregating 1:1:1:1) and partially informative markers (or missing markers, segregating 1:2:1, 3:1, and 1:1) in a full-sib family derived from two outbred parent plants. The characterization of linkage phases is based on the posterior probability distribution of the assignment of alternative alleles at given markers to two homologous chromosomes of each parent, conditional on the observed phenotypes of the markers. Two- and multi-point analyses are performed to estimate the recombination fraction and determine the most likely linkage phase between different types of markers. A numerical example is presented to demonstrate the statistical properties of the model for characterizing the linkage phase between markers.}, number={3}, journal={THEORETICAL POPULATION BIOLOGY}, author={Wu, RL and Ma, CX and Painter, I and Zeng, ZB}, year={2002}, month={May}, pages={349–363} } @article{wu_gallo-meagher_littell_zeng_2001, title={A general polyploid model for analyzing gene segregation in outcrossing tetraploid species}, volume={159}, number={2}, journal={Genetics}, author={Wu, R. L. and Gallo-Meagher, M. and Littell, R. C. and Zeng, Z. B.}, year={2001}, pages={869–882} } @article{wu_wu_ma_zeng_yang_casella_2001, title={A multivalent pairing model of linkage analysis in autotetraploids}, volume={159}, number={3}, journal={Genetics}, author={Wu, S. S. and Wu, R. L. and Ma, C. X. and Zeng, Z. B. and Yang, M. C. and Casella, G.}, year={2001}, pages={1339–1350} } @article{weber_eisman_higgins_morey_patty_tausek_zeng_2001, title={An analysis of polygenes affecting wing shape on chromosome 2 in Drosophila melanogaster}, volume={159}, number={3}, journal={Genetics}, author={Weber, K. and Eisman, R. and Higgins, S. and Morey, L. and Patty, A. and Tausek, M. and Zeng, Z. B.}, year={2001}, pages={1045–1057} } @article{wu_zeng_2001, title={Joint linkage and linkage disequilibrium mapping in natural populations}, volume={157}, number={2}, journal={Genetics}, author={Wu, R. L. and Zeng, Z. B.}, year={2001}, pages={899–909} } @article{yin_huang_wang_zhu_zeng_wu_2001, title={Preliminary interspecific genetic maps of the Populus genome constructed from RAPD markers}, volume={44}, ISSN={["0831-2796"]}, DOI={10.1139/gen-44-4-602}, number={4}, journal={GENOME}, author={Yin, TM and Huang, MR and Wang, MX and Zhu, LH and Zeng, ZB and Wu, RL}, year={2001}, month={Aug}, pages={602–609} } @inbook{zeng_2001, title={QTL Mapping}, ISBN={9780122270802}, url={http://dx.doi.org/10.1006/rwgn.2001.1441}, DOI={10.1006/rwgn.2001.1441}, booktitle={Encyclopedia of Genetics}, publisher={Elsevier}, author={Zeng, Z.-B.}, year={2001}, pages={1587–1593} } @inbook{zeng_2001, place={London, UK}, title={Quantitative trait loci: statistical methods for mapping their positions}, ISBN={9781884964343}, booktitle={Encyclopedia of Genetics}, publisher={Fitzroy Dearborn Publishers}, author={Zeng, Z.-B.}, editor={Reeve, Eric C.R. and Black, IsobelEditors}, year={2001} } @article{liu_zeng_2000, title={A general mixture model approach for mapping quantitative trait loci from diverse cross designs involving multiple inbred lines}, volume={75}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672300004493}, abstractNote={Most current statistical methods developed for mapping quantitative trait loci (QTL) based on inbred line designs apply to crosses from two inbred lines. Analysis of QTL in these crosses is restricted by the parental genetic differences between lines. Crosses from multiple inbred lines or multiple families are common in plant and animal breeding programmes, and can be used to increase the efficiency of a QTL mapping study. A general statistical method using mixture model procedures and the EM algorithm is developed for mapping QTL from various cross designs of multiple inbred lines. The general procedure features three cross design matrices, W, that define the contribution of parental lines to a particular cross and a genetic design matrix, D, that specifies the genetic model used in multiple line crosses. By appropriately specifying W matrices, the statistical method can be applied to various cross designs, such as diallel, factorial, cyclic, parallel or arbitrary-pattern cross designs with two or multiple parental lines. Also, with appropriate specification for the D matrix, the method can be used to analyse different kinds of cross populations, such as F2 backcross, four-way cross and mixed crosses (e.g. combining backcross and F2). Simulation studies were conducted to explore the properties of the method, and confirmed its applicability to diverse experimental designs.}, number={3}, journal={GENETICAL RESEARCH}, author={Liu, YF and Zeng, ZB}, year={2000}, month={Jun}, pages={345–355} } @article{wu_han_hu_fang_li_li_zeng_2000, title={An integrated genetic map of Populus deltoides based on amplified fragment length polymorphisms}, volume={100}, ISSN={["0040-5752"]}, DOI={10.1007/s001220051431}, number={8}, journal={THEORETICAL AND APPLIED GENETICS}, author={Wu, RL and Han, YF and Hu, JJ and Fang, JJ and Li, L and Li, ML and Zeng, ZB}, year={2000}, month={Jun}, pages={1249–1256} } @article{zeng_liu_stam_kao_mercer_laurie_2000, title={Genetic architecture of a morphological shape difference between two Drosophila species}, volume={154}, number={1}, journal={Genetics}, author={Zeng, Z. B. and Liu, J. J. and Stam, L. F. and Kao, C. H. and Mercer, J. M. and Laurie, C. C.}, year={2000}, pages={299–310} } @article{vieira_pasyukova_zeng_hackett_lyman_mackay_2000, title={Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster}, volume={154}, number={1}, journal={Genetics}, author={Vieira, C. and Pasyukova, E. G. and Zeng, Z. B. and Hackett, J. B. and Lyman, R. F. and Mackay, T. F. C.}, year={2000}, pages={213–227} } @article{luo_tao_zeng_2000, title={Inferring linkage disequilibrium between a polymorphic marker locus and a trait locus in natural populations}, volume={156}, number={1}, journal={Genetics}, author={Luo, Z. W. and Tao, S. H. and Zeng, Z. B.}, year={2000}, pages={457–467} } @inbook{wu_li_zeng_2000, title={Molecular dissection of quantitative traits: new perspectives from populus}, volume={1}, booktitle={Molecular biology of woody plants}, publisher={Dordrecht; Boston: Kluwer Academic}, author={Wu, R. and Li, B. and Zeng, Z.-B.}, editor={Jain, S. M. and Minocha, S. C.Editors}, year={2000}, pages={475–490} } @article{rongling_zeng_mckeand_o'malley_2000, title={The case for molecular mapping in forest tree breeding}, volume={19}, number={2000}, journal={Plant Breeding Reviews}, author={Rongling, W. and Zeng, Z.-B. and McKeand and O'Malley, D. M.}, year={2000}, pages={41–68} } @article{weber_eisman_morey_patty_sparks_tausek_zeng_1999, title={An analysis of polygenes affecting wing shape on chromosome 3 in Drosophila melanogaster}, volume={153}, number={2}, journal={Genetics}, author={Weber, K. and Eisman, R. and Morey, L. and Patty, A. and Sparks, J. and Tausek, M. and Zeng, Z. B.}, year={1999}, pages={773–786} } @article{zeng_kao_basten_1999, title={Estimating the genetic architecture of quantitative traits}, volume={74}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672399004255}, abstractNote={Understanding and estimating the structure and parameters associated with the genetic architecture of quantitative traits is a major research focus in quantitative genetics. With the availability of a well-saturated genetic map of molecular markers, it is possible to identify a major part of the structure of the genetic architecture of quantitative traits and to estimate the associated parameters. Multiple interval mapping, which was recently proposed for simultaneously mapping multiple quantitative trait loci (QTL), is well suited to the identification and estimation of the genetic architecture parameters, including the number, genomic positions, effects and interactions of significant QTL and their contribution to the genetic variance. With multiple traits and multiple environments involved in a QTL mapping experiment, pleiotropic effects and QTL by environment interactions can also be estimated. We review the method and discuss issues associated with multiple interval mapping, such as likelihood analysis, model selection, stopping rules and parameter estimation. The potential power and advantages of the method for mapping multiple QTL and estimating the genetic architecture are discussed. We also point out potential problems and difficulties in resolving the details of the genetic architecture as well as other areas that require further investigation. One application of the analysis is to improve genome-wide marker-assisted selection, particularly when the information about epistasis is used for selection with mating.}, number={3}, journal={GENETICAL RESEARCH}, author={Zeng, ZB and Kao, CH and Basten, CJ}, year={1999}, month={Dec}, pages={279–289} } @article{kao_zeng_teasdale_1999, title={Multiple interval mapping for quantitative trait loci}, volume={152}, number={3}, journal={Genetics}, author={Kao, C. H. and Zeng, Z. B. and Teasdale, R. D.}, year={1999}, pages={1203–1216} } @article{zeng_1997, title={Combining information from data in mapping analysis: use of multiple markers and multiple traits}, volume={8}, DOI={10.1080/10495399709525876}, number={1}, journal={Animal Biotechnology}, author={Zeng, Z. B.}, year={1997}, pages={145–150} } @article{kao_zeng_1997, title={General formulas for obtaining the MLEs and the asymptotic variance-covariance matrix in mapping quantitative trait loci when using the EM algorithm}, volume={53}, ISSN={["0006-341X"]}, DOI={10.2307/2533965}, abstractNote={We present in this paper general formulas for deriving the maximum likelihood estimates and the asymptotic variance-covariance matrix of the positions and effects of quantitative trait loci (QTLs) in a finite normal mixture model when the EM algorithm is used for mapping QTLs. The general formulas are based on two matrices D and Q, where D is the genetic design matrix, characterizing the genetic effects of the QTLs, and Q is the conditional probability matrix of QTL genotypes given flanking marker genotypes, containing the information on QTL positions. With the general formulas, it is relatively easy to extend QTL mapping analysis to using multiple marker intervals simultaneously for mapping multiple QTLs, for analyzing QTL epistasis, and for estimating the heritability of quantitative traits. Simulations were performed to evaluate the performance of the estimates of the asymptotic variances of QTL positions and effects.}, number={2}, journal={BIOMETRICS}, author={Kao, CH and Zeng, ZB}, year={1997}, month={Jun}, pages={653–665} } @article{jiang_zeng_1997, title={Mapping quantitative trait loci with dominant and missing markers in various crosses from two inbred lines}, volume={101}, ISSN={["0016-6707"]}, DOI={10.1023/A:1018394410659}, abstractNote={Dominant phenotype of a genetic marker provides incomplete information about the marker genotype of an individual. A consequence of using this incomplete information for mapping quantitative trait loci (QTL) is that the inference of the genotype of a putative QTL flanked by a marker with dominant phenotype will depend on the genotype or phenotype of the next marker. This dependence can be extended further until a marker genotype is fully observed. A general algorithm is derived to calculate the probability distribution of the genotype of a putative QTL at a given genomic position, conditional on all observed marker phenotypes in the region with dominant and missing marker information for an individual. The algorithm is implemented for various populations stemming from two inbred lines in the context of mapping QTL. Simulation results show that if only a proportion of markers contain missing or dominant phenotypes, QTL mapping can be almost as efficient as if there were no missing information in the data. The efficiency of the analysis, however, may decrease substantially when a very large proportion of markers contain missing or dominant phenotypes and a genetic map has to be reconstructed first on the same data as well. So it is important to combine dominant markers with codominant markers in a QTL mapping study.}, number={1}, journal={GENETICA}, author={Jiang, CJ and Zeng, ZB}, year={1997}, pages={47–58} } @book{basten_weir_zeng_1997, title={QTL Cartographer: a reference manual and tutorial for QTL mapping}, publisher={Department of Statistics, NC State University}, author={Basten, C.J. and Weir, B.S. and Zeng, Z.-B.}, year={1997} } @article{true_liu_stam_zeng_laurie_1997, title={Quantitative genetic analysis of divergence in male secondary sexual traits between Drosophila simulans and Drosophila mauritiana}, volume={51}, ISSN={["0014-3820"]}, DOI={10.2307/2411157}, number={3}, journal={EVOLUTION}, author={True, JR and Liu, JJ and Stam, LF and Zeng, ZB and Laurie, CC}, year={1997}, month={Jun}, pages={816–832} } @article{nuzhdin_pasyukova_dilda_zeng_mackay_1997, title={Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster}, volume={94}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.94.18.9734}, abstractNote={ Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms. Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life. Analyses of Drosophila spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late-age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis. The QTLs had large sex-specific effects on lifespan and age-specific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects. Late age-of-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan. }, number={18}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Nuzhdin, SV and Pasyukova, EG and Dilda, CL and Zeng, ZB and Mackay, TFC}, year={1997}, month={Sep}, pages={9734–9739} } @article{doerge_zeng_weir_1997, title={Statistical issues in the search for genes?}, volume={12}, number={1997}, journal={Statistical Science}, author={Doerge, R. W. and Zeng, Z. B. and Weir, B. S.}, year={1997}, pages={195–219} } @article{cockerham_zeng_1996, title={Design III with marker loci}, volume={143}, DOI={10.1093/genetics/143.3.1437}, abstractNote={Abstract Design III is an experimental design originally proposed by R. E. Comstock and H. F. Robinson for estimating genetic variances and the average degree of dominance for quantitative trait loci (QTL) and has recently been extended for mapping QTL. In this paper, we first extend Comstock and Robinson's analysis of variance to include linkage, two-locus epistasis and the use of F 3 parents. Then we develop the theory and statistical analysis of orthogonal contrasts and contrast × environment interaction for a single marker locus to characterize the effects of QTL. The methods are applied to the maize data of C. W. Stuber. The analyses strongly suggest that there are multiple linked QTL in many chromosomes for several traits examined. QTL effects are largely environment-independent for grain yield, ear height, plant height and ear leaf area and largely environment dependent for days to tassel, grain moisture and ear number. There is significant QTL epistasis. The results are generally in favor of the hypothesis of dominance of favorable genes to explain the observed heterosis in grain yield and other traits, although epistasis could also play an important role and overdominance at individual QTL level can not be ruled out.}, number={3}, journal={Genetics}, author={Cockerham, C.C. and Zeng, Z.-B.}, year={1996}, month={Jul}, pages={1437–1456} } @article{liu_mercer_stam_gibson_zeng_laurie_1996, title={Genetic analysis of a morphological shape difference in the male genitalia of Drosophila simulans and D. mauritiana}, volume={142}, DOI={10.1093/genetics/142.4.1129}, abstractNote={Abstract Two closely related species of Drosophila, D. simulans and D. mauritiana, differ markedly in morphology of the posterior lobe of the male genital arch. Both size and shape aspects of lobe variation can be quantified by a morphometric descriptor based on elliptical Fourier and principal components analyses. The genetic architecture of this quantitative trait (PC1) was investigated by hybridizing inbred lines to produce two backcross populations of ~200 individuals each, which were analyzed jointly by a composite interval mapping procedure with the aid of 18 marker loci. The parental lines show a large difference in PC1 (30.4 environmental standard deviations), and the markers account for >80% of the phenotypic variation in backcross populations. Eight of 15 intervals analyzed show convincing evidence of quantitative trait loci (QTL), and the range of estimated QTL effects is 5.7–15.9% of the parental difference (1.7–4.8 environmental standard deviations). These estimates may represent the joint effects of multiple QTL within a single interval (which averaged 23 cM in length). Although there is some evidence of partial dominance of mauritiana alleles and for epistasis, the pattern of inheritance is largely additive.}, number={4}, journal={Genetics}, author={Liu, J. and Mercer, J.M. and Stam, L.F. and Gibson, G.C. and Zeng, Z.-B. and Laurie, C.C.}, year={1996}, month={Apr}, pages={1129–1145} } @article{zeng_weir_1996, title={Statistical methods for mapping quantitative trait loci}, volume={22}, journal={Acta Agronomica Sinica}, author={Zeng, Z.-B. and Weir, B.S.}, year={1996}, pages={535–549} } @article{dragani_zeng_canzian_gariboldi_ghilarducci_manenti_pierotti_1995, title={Mapping of body weight loci on mouse Chromosome X}, volume={6}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/bf00539002}, DOI={10.1007/bf00539002}, abstractNote={Inheritance of overweight in humans appears to be under polygenic control. Study on the mouse model may help to determine candidate regions in human genome for the search of overweight genes. Inbred mouse strains showed wide variation in body weight and can provide an experimental model for the study of inheritance of overweight. By genetic linkage analysis, we report the mapping of two loci, named Bw1 and Bw2 (body weight 1 and 2), on Chromosome (Chr) X that strongly affect adult body weight in two interspecific testcross male populations (HSB) and ASB) of mice. In addition, another locus, named Bw3, is also mapped on Chr X in ASB populations. These loci account for up to 24% of the phenotypic variation in both populations. Considering the conserved synteny between mouse and humans Chr X, these results provide candidate regions on Chr X that can be tested for linkage with overweight in humans.}, number={11}, journal={Mammalian Genome}, publisher={Springer Nature}, author={Dragani, T. A. and Zeng, Z.-B. and Canzian, F. and Gariboldi, M. and Ghilarducci, M. T. and Manenti, G. and Pierotti, M. A.}, year={1995}, month={Nov}, pages={778–781} } @article{jiang_zeng_1995, title={Multiple-trait analysis of genetic-mapping for quantitative trait loci}, volume={140}, number={3}, journal={Genetics}, author={Jiang, C. J. and Zeng, Z. B.}, year={1995}, pages={1111–1127} } @inproceedings{zeng_1994, title={A composite interval mapping method for locating multiple QTLs}, volume={21}, booktitle={Proceedings of the 5th World Congress on Genetics Applied to Livestock Production}, author={Zeng, Z.-B.}, year={1994}, pages={37–40} } @article{zeng_1994, title={Precision mapping of quantitative trait loci}, volume={136}, number={4}, journal={Genetics}, author={Zeng, Z. B.}, year={1994}, pages={1457–1468} } @inproceedings{basten_weir_zeng_1994, title={ZMAP---A QTL Cartographer}, volume={22}, booktitle={Proceedings of the 5th World Congress on Genetics Applied to Livestock Production}, author={Basten, C.J. and Weir, B.S. and Zeng, Z.-B.}, year={1994}, pages={65–66} } @article{zeng_cockerham_1993, title={Mutation models and quantitative genetic variation}, volume={133}, number={3}, journal={Genetics}, author={Zeng, Z. B. and Cockerham, C. C.}, year={1993}, pages={729} } @article{zeng_1993, title={THEORETICAL BASIS FOR SEPARATION OF MULTIPLE LINKED GENE EFFECTS IN MAPPING QUANTITATIVE TRAIT LOCI}, volume={90}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.90.23.10972}, abstractNote={It is now possible to use complete genetic linkage maps to locate major quantitative trait loci (QTLs) on chromosome regions. The current methods of QTL mapping (e.g., interval mapping, which uses a pair or two pairs of flanking markers at a time for mapping) can be subject to the effects of other linked QTLs on a chromosome because the genetic background is not controlled. As a result, mapping of QTLs can be biased, and the resolution of mapping is not very high. Ideally when we test a marker interval for a QTL, we would like our test statistic to be independent of the effects of possible QTLs at other regions of the chromosome so that the effects of QTLs can be separated. This test statistic can be constructed by using a pair of markers to locate the testing position and at the same time using other markers to control the genetic background through a multiple regression analysis. Theory is developed in this paper to explore the idea of a conditional test via multiple regression analysis. Various properties of multiple regression analysis in relation to QTL mapping are examined. Theoretical analysis indicates that it is advantageous to construct such a testing procedure for mapping QTLs and that such a test can potentially increase the precision of QTL mapping substantially.}, number={23}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={ZENG, ZB}, year={1993}, month={Dec}, pages={10972–10976} } @article{zeng_1992, title={Correcting the bias of Wright's estimates of the number of genes affecting a quantitative character: A further improved method}, volume={131}, number={4}, journal={Genetics}, author={Zeng, Z. B.}, year={1992}, pages={987} } @article{zeng_cockerham_1991, title={Variance of neutral genetic variances within and between populations for a quantitative character}, volume={129}, number={2}, journal={Genetics}, author={Zeng, Z. B. and Cockerham, C. C.}, year={1991}, pages={535} } @inproceedings{zeng_tachida_1990, title={How important is mutation for selection responses?}, volume={13}, booktitle={Proceedings of the 4th World Congress on Genetics Applied to Livestock Production}, author={Zeng, Z.-B. and Tachida, H.}, year={1990}, pages={301–305} } @article{zeng_houle_cockerham_1990, title={How informative is Wright's estimator of the number of genes affecting a quantitative character?}, volume={126}, number={1}, journal={Genetics}, author={Zeng, Z. B. and Houle, D. and Cockerham, C. C.}, year={1990}, pages={235} } @article{zeng_cockerham_1990, title={LONG-TERM RESPONSE TO ARTIFICIAL SELECTION WITH MULTIPLE ALLELES - STUDY BY SIMULATIONS}, volume={37}, ISSN={["1096-0325"]}, DOI={10.1016/0040-5809(90)90039-X}, abstractNote={The effect of multiple alleles on long-term response to selection is examined by simulations using a pseudosampling technique to simulate the multidimensional diffusion process. The effects of alleles are independently drawn from a normal distribution and the initial frequencies of alleles are assumed either to be equal or to be drawn from a neutral equilibrium population. With these two initial gene frequency distributions we examined various properties of the selection response process for the effects of number of alleles and selection intensity. For neutral initial frequencies the effects of multiple alleles compared with two alleles are minor on the ratio of final to initial response (E(R infinity/E(R1)) and the half life of response (t0.5), but are significant on the variance of response. Under certain conditions the variance of the selection limit can even increase as selection gets stronger. For equal initial frequencies the effects of multiple alleles are, however, minor on the ratio of the variance of the selection limit to the initial genetic variance, but E(R infinity/E(R1) and t0.5 increase as the number of alleles increases. The results show that for certain statistics the effects of multiple alleles can be minimized by an appropriate transformation of parameters for given initial gene frequencies, but the effects cannot, in general, be removed by any single transformation or reparameterization of parameters.}, number={1}, journal={THEORETICAL POPULATION BIOLOGY}, author={ZENG, ZB and COCKERHAM, CC}, year={1990}, month={Feb}, pages={254–272} } @article{zeng_1989, title={A GENETIC MODEL OF INTERPOPULATION VARIATION AND COVARIATION OF QUANTITATIVE CHARACTERS}, volume={53}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672300028196}, abstractNote={Summary}, number={3}, journal={GENETICS RESEARCH}, author={ZENG, ZB}, year={1989}, month={Jun}, pages={215–221} } @article{zeng_tachida_cockerham_1989, title={Effects of mutation on selection limits in finite populations with multiple alleles}, volume={122}, number={4}, journal={Genetics}, author={Zeng, Z. B. and Tachida, H. and Cockerham, C. C.}, year={1989}, pages={977} } @article{zeng_1988, title={Long-Term Correlated Response, Interpopulation Covariation, and Interspecific Allometry}, volume={42}, ISSN={0014-3820}, url={http://dx.doi.org/10.2307/2409239}, DOI={10.2307/2409239}, number={2}, journal={Evolution}, publisher={JSTOR}, author={Zeng, Zhao-Bang}, year={1988}, month={Mar}, pages={363} } @article{zeng_1987, title={Genotypic distribution at the limits to natural and artificial selection with mutation}, volume={32}, ISSN={0040-5809}, url={http://dx.doi.org/10.1016/0040-5809(87)90042-6}, DOI={10.1016/0040-5809(87)90042-6}, abstractNote={A general procedure for analysing the change of genotypic distributions under stabilizing and truncation selection is described here and used to investigate the genotypic distribution at the limits to selection. For comparison, a simple approximate procedure using a normal distribution is also presented. It is clear that in the long term truncation introduces departures from normality mainly through gene frequency change, rather than through the generation of linkage disequilibrium under random mating. The Gaussian approximation performs reasonably well for additive gene effects unless the mean gene frequency is very extreme (say, outside the range of 0.05 to 0.95) and the number of loci is small (say, less then 50) regardless of the type of selection in operation. The genotypic distribution at the limits to selection largely depends on the type of limit reached. If a limit is obtained due to the action of natural selection before the exhaustion of existing variation, the distribution will normally not be very skew, but if a limit is reached at which mutation plays a central role in the maintenance of genetic variability, it could have high coefficients of skewness and kurtosis. The role of mutation on the long-term response is also discussed.}, number={1}, journal={Theoretical Population Biology}, publisher={Elsevier BV}, author={Zeng, Zhao-Bang}, year={1987}, month={Aug}, pages={90–113} } @article{zeng_hill_1986, title={The selection limit due to the conflict between truncation and stabilizing selection with mutation}, volume={114}, journal={Genetics}, author={Zeng, Z.-B. and Hill, W.G.}, year={1986}, pages={1313–1328} } @phdthesis{zeng_1986, title={Theoretical studies on genetic limits to natural and artificial selection with mutation}, school={Department of Genetics, The University of Edinburgh}, author={Zeng, Z.-B.}, year={1986} }