Rongling Wu - Academia.edu (original) (raw)

Papers by Rongling Wu

American Journal of Hypertension

The effects of genistein on the blood pressure of angiotensin-treated hypertensive rats were stud... more The effects of genistein on the blood pressure of angiotensin-treated hypertensive rats were studied in correlation with the ERK-MAPK activity and the production of superoxyde anion radical in the aortic tissue. Hypertension was induced in Sprague-Dawley rats by a treatment of angiotensin II (200ng/kg/hour) with osmotic pumps for a period of 12 days. The genistein (0.17mg/kg/hour) was given following the same procedure. The average arterial pressure was monitored every other day by a tail-cuff method. The superoxyde anion radical concentration was measured by lucegenin-enhanced chemiluminescence technique. The activity of ERK-MAPK pathway was measured by western blot. An increase of arterial pressure of 27% was observed (141.8Ϯ7.49 to 180.6Ϯ2.7mmHg, pϽ0.05) after 12 days in the angiotensin-treated rats compared to controls. When these hypertensive rats were treated with genistein which inhibit tyrosine kinase, the increase in pressure was attenuated to only 9.5%(141.8Ϯ7.49 to 155.3Ϯ1.0mmHg, pϽ0.05). The concentration of the superoxyde anion radical in the aortic tissues of hypertensive rats increased by 235% compared to controls(2360.4Ϯ443 to 7904.5Ϯ883.5cpm, pϽ0.05). When treated with genistein, this increase was lowered to 96%(2360.4Ϯ443 to 4619.5Ϯ224.5cpm, pϽ0.05). Finally, the ERK-MAPK activity was 1.45Ϯ0.12 (pϽ0.05) times greater in tissues from rats treated with angiotensin II alone. The levels of ERK-MAPK activation were similar in tissues from rats treated with genistein and normotensive controls. Our results show that the blockade of tyrosine kinase pathway with genistein can attenuate significantly the increase in blood pressure induced by angiotensin II. It was also shown that the effect of genistein on the increase of blood pressure may be linked to a decrease in the activity of the ERK-MAPK pathway and in the production of the superoxyde anion radical in the aortic tissues. These results suggest a possible implication of ERK-MAPK pathway and superoxyde anion radical modulation in angiotensin-induced hypertension.

Genome-wide analysis of salt-responsive and novel microRNAs in Populus euphratica by deep sequencing

BMC genetics, 2014

Populus euphratica is a representative model woody plant species for studying resistance to abiot... more Populus euphratica is a representative model woody plant species for studying resistance to abiotic stresses such as drought and salt. Salt stress is one of the most common environmental factors that affect plant growth and development. MicroRNAs (miRNAs) are small, noncoding RNAs that have important regulatory functions in plant growth, development, and response to abiotic stress. To investigate the miRNAs involved in the salt-stress response, we constructed four small cDNA libraries from P. euphratica plantlets treated with or without salt (300 mM NaCl, 3 days) in either the root or leaf. Using high-throughput sequencing to identify miRNAs, we found 164 conserved miRNAs belonging to 44 families. Of these, 136 novel miRNAs were from the leaf, and 128 novel miRNAs were from the root. In response to salt stress, 95 miRNAs belonging to 46 conserved miRNAs families changed significantly, with 56 miRNAs upregulated and 39 miRNAs downregulated in the leaf. A comparison of the leaf and ro...

De Novo Assembly and Characterization of the Fruit Transcriptome of Chinese Jujube (Ziziphus jujuba Mill.) Using 454 Pyrosequencing and the Development of Novel Tri-Nucleotide SSR Markers

PLoS ONE, 2014

Current Genomics, 2014

By measuring gene expression at an unprecedented resolution and throughput, RNA-seq has played a ... more By measuring gene expression at an unprecedented resolution and throughput, RNA-seq has played a pivotal role in studying biological functions. Its typical application in clinical medicine is to identify the discrepancies of gene expression between two different types of cancer cells, sensitive and resistant to chemotherapeutic treatment, in a hope to predict drug response. Here we modified and used a mechanistic model to identify distinct patterns of gene expression in response of different types of breast cancer cell lines to chemotherapeutic treatment. This model was founded on a mixture likelihood of Poisson-distributed transcript read data, with each mixture component specified by the Skellam function. By estimating and comparing the amount of gene expression in each environment, the model can test how genes alter their expression in response to environment and how different genes interact with each other in the responsive process. Using the modified model, we identified the alternations of gene expression between two cell lines of breast cancer, resistant and sensitive to tamoxifen, which allows us to interpret the expression mechanism of how genes respond to metabolic differences between the two cell types. The model can have a general implication for studying the plastic pattern of gene expression across different environments measured by RNA-seq.

Journal of Theoretical Biology, 2011

All biological phenomena occurring at different levels of organization from cells to organisms ca... more All biological phenomena occurring at different levels of organization from cells to organisms can be modeled as a dynamic system, in which the underlying components interact dynamically to comprehend its biological function. Such a systems modeling approach facilitates the use of biochemically and biophysically detailed mathematical models to describe and quantify ''living cells,'' leading to an in-depth and precise understanding of the behavior, development and function of a biological system. Here, we illustrate how this approach can be used to map genes or quantitative trait loci (QTLs) that control a complex trait using the example of the circadian rhythm system which has been at the forefront of analytical mathematical modeling for many years. We integrate a system of biologically meaningful delay differential equations (DDEs) into functional mapping, a statistical model designed to map dynamic QTLs involved in biological processes. The DDEs model the ability of circadian rhythm to generate autonomously sustained oscillations with a period close to 24 h, in terms of timevarying mRNA and protein abundances. By incorporating the Runge-Kutta fourth order algorithm within the likelihood-based context of functional mapping, we estimated the genetic parameters that define the periodic pattern of QTL effects on time-varying mRNA and protein abundances and their dynamic association as well as the linkage disequilibrium of the QTL and a marker. We prove theorems about how to choose appropriate parameters to guarantee periodic oscillations. We further used simulation studies to investigate how a QTL influences the period and the amplitude of circadian oscillations through changing model parameters. The model provides a quantitative framework for assessing the interplay between genetic effects of QTLs and rhythmic responses.

A Mechanistic Model for Genetic Machinery of Ontogenetic Growth

Genetics, 2004

Two different genetic mechanisms can be proposed to explain variation in growth trajectories. The... more Two different genetic mechanisms can be proposed to explain variation in growth trajectories. The allelic sensitivity hypothesis states that growth trajectory is controlled by the time-dependent expression of alleles at the deterministic quantitative trait loci (dQTL) formed during embryogenesis. The gene regulation hypothesis states that the differentiation in growth process is due to the opportunistic quantitative trait loci (oQTL) through their mediation with new developmental signals. These two hypotheses of genetic control have been elucidated in the literature. Here, we propose a new statistical model for discerning these two mechanisms in the context of growth trajectories by integrating growth laws within a QTL-mapping framework. This model is developed within the maximum-likelihood context, implemented with a grid approach for estimating the genomic positions of the deterministic and opportunistic QTL and the simplex algorithm for estimating the growth curve parameters of t...

Statistical model for characterizing epistatic control of triploid endosperm triggered by maternal and offspring QTLs

Genetical Research, 2005

To study the effects of maternal and endosperm quantitative trait locus (QTL) interaction on endo... more To study the effects of maternal and endosperm quantitative trait locus (QTL) interaction on endosperm development, we derive a two-stage hierarchical statistical model within the maximum-likelihood context, implemented with an expectation-maximization algorithm. A model incorporating both maternal and offspring marker information can improve the accuracy and precision of genetic mapping. Extensive simulations under different sampling strategies, heritability levels and gene action modes were performed to investigate the statistical properties of the model. The QTL location and parameters are better estimated when two QTLs are located at different intervals than when they are located at the same interval. Also, the additive effect of the offspring QTLs is better estimated than the additive effect of the maternal QTLs. The implications of our model for agricultural and evolutionary genetic research are discussed.

Network Models for Dissecting Plant Development by Functional Mapping

Current Bioinformatics, 2009

BioScience, 2003

Allometric power scaling, ontogenetic growth, and phenotypic plasticity represent three fundament... more Allometric power scaling, ontogenetic growth, and phenotypic plasticity represent three fundamental developmental features for every living organism. To analyze these three features of an organism at the interface between development and evolution, researchers must understand their underlying genetic bases. We have developed a general framework for deciphering the genetic machinery that guides allometric scaling, ontogenetic growth, and environment-dependent plasticity in biological organisms. This approach constitutes a step toward creating a unified view of evolutionary biology and developmental biology ("evo-devo").

Bioinformatics, 2007

Motivation: Genetic interactions or epistasis may play an important role in the genetic etiology ... more Motivation: Genetic interactions or epistasis may play an important role in the genetic etiology of drug response. With the availability of large-scale, high-density single nucleotide polymorphism markers, a great challenge is how to associate haplotype structures and complex drug response through its underlying pharmacodynamic mechanisms. Results: We have derived a general statistical model for detecting an interactive network of DNA sequence variants that encode pharmacodynamic processes based on the haplotype map constructed by single nucleotide polymorphisms. The model was validated by a pharmacogenetic study for two predominant beta-adrenergic receptor (AR) subtypes expressed in the heart, 1AR and 2AR. Haplotypes from these two receptors trigger significant interaction effects on the response of heart rate to different dose levels of dobutamine. This model will have implications for pharmacogenetic and pharmacogenomic research and drug discovery.

BMC genetics, 2014

Mei, Prunus mume Sieb. et Zucc., is an ornamental plant popular in East Asia and, as an important... more Mei, Prunus mume Sieb. et Zucc., is an ornamental plant popular in East Asia and, as an important member of genus Prunus, has played a pivotal role in systematic studies of the Rosaceae. However, the genetic architecture of botanical traits in this species remains elusive. This paper represents the first genome-wide mapping study of quantitative trait loci (QTLs) that affect stem growth and form, leaf morphology and leaf anatomy in an intraspecific cross derived from two different mei cultivars. Genetic mapping based on a high-density linkage map constricted from 120 SSRs and 1,484 SNPs led to the detection of multiple QTLs for each trait, some of which exert pleiotropic effects on correlative traits. Each QTL explains 3-12% of the phenotypic variance. Several leaf size traits were found to share common QTLs, whereas growth-related traits and plant form traits might be controlled by a different set of QTLs. Our findings provide unique insights into the genetic control of tree growth...

Theoretical Population Biology, 2002

Polyploids can be classified as either allopolyploids or autopolyploids based on their presumed o... more Polyploids can be classified as either allopolyploids or autopolyploids based on their presumed origins. From a perspective of linkage analysis, however, the nature of polyploids can be better described as bivalent polyploids, in which two chromosomes pair at meiosis, multivalent polyploids, in which more than two chromosomes pair, and general polyploids, in which bivalent and multivalent formations occur simultaneously. In this paper, we develop a statistical method for linkage analysis of polymorphic markers in bivalent polyploids. This method takes into account a unique cytological pairing mechanism for the formation of diploid gametes in tetraploids}preferential bivalent pairings at meiosis during which two homologous chromosomes pair with a higher probability than two homoeologous chromosomes. The higher frequency of homologous over homoeologous pairing, defined as the preferential pairing factor, affects the segregation patterns and linkage analysis of different genes on the same chromosome. A maximum likelihood method implemented with the EM algorithm is proposed to simultaneously estimate linkage and parental linkage phases over a pair of markers from any possible marker cross type between two outbred bivalent tetraploid parents demonstrating preferential bivalent pairings. Simulation studies display that the method can be well used to estimate the recombination fraction between different marker types and the preferential pairing factor typical of bivalent tetraploids. The implications of this method for current genome projects in polyploid species are discussed.

Theoretical and Applied Genetics, 2011

Quality protein maize (QPM) is a high lysinecontaining corn that is based on genetic modification... more Quality protein maize (QPM) is a high lysinecontaining corn that is based on genetic modification of the opaque2 (o2) mutant. In QPM, modifier genes convert the starchy endosperm of o2 to the vitreous phenotype of wild type maize. There are multiple, unlinked o2 modifier loci (Opm) in QPM and their nature and mode of action are unknown. We previously identified seven Opm QTLs and characterized 16 genes that are differentially up-regulated at a significant level in K0326Y QPM, compared to the starchy endosperm mutant W64Ao2. In order to further characterize these Opm QTLs and the genes up-regulated in K0326Y QPM, we created a population of 314 recombinant inbred lines (RILs) from a cross between K0326Y QPM and W64Ao2. The RILs were characterized for three traits associated with endosperm texture: vitreousness, density and hardness. Genetic linkage analysis of the RIL population confirmed three of the previously identified QTLs associated with o2 endosperm modification in K0326Y QPM. Many of the genes up-regulated in K0326Y QPM showed substantially higher levels of expression in vitreous compared with opaque RILs. These included genes associated with the upstream regulation of the ethylene response pathway, and a gene encoding a regulatory Communicated by C. Schön.

A statistical model for high-resolution mapping of quantitative trait loci determining HIV dynamics

Statistics in Medicine, 2004

Are there specific genes that control the pathogenesis of HIV infection? This question, which is ... more Are there specific genes that control the pathogenesis of HIV infection? This question, which is of fundamental importance in designing personalized strategies of gene therapy to control HIV infection, can be examined by genetic mapping approaches. In this article, we present a new statistical model for unravelling the genetic mechanisms for the dynamic change of HIV that causes AIDS by marker-based linkage disequilibrium (LD) analyses. This new model is the extension of our functional mapping theory to integrate viral load trajectories within a genetic mapping framework. Earlier studies of HIV dynamics have led to various mathematical functions for modelling the kinetic curves of plasma virions and CD4 lymphocytes in HIV patients. Through incorporating these functions into the LD-based mapping procedure, we can identify and map individual quantitative trait loci (or QTL) responsible for viral pathogenesis. We derive a closed-form solution for estimating QTL allele frequency and marker-QTL linkage disequilibrium in the context of EM algorithm and implement the simplex algorithm to estimate the mathematical parameters describing the curve shapes of HIV pathogenesis. We performed different simulation scenarios based on currently used clinical designs in AIDS/HIV research to illustrate the utility and power of our model for genetic mapping of HIV dynamics. The implications of our model for genetic and genomic research into AIDS pathogenesis are discussed.

Candidate gene polymorphisms (BoIFNG, TLR4, SLC11A1) as risk factors for paratuberculosis infection in cattle

Preventive Veterinary Medicine, 2009

The extent and distribution of linkage disequilibrium in a multi-hierarchic outbred canine pedigree

Mammalian Genome, 2003

A disequilibrium model for detecting genetic mutations for cancer

Journal of Theoretical Biology, 2010

A dynamic model for genome-wide association studies

Human Genetics, 2011

A nonlinear mixed-effect mixture model for functional mapping of dynamic traits

Heredity, 2008

An algorithmic model for constructing a linkage and linkage disequilibrium map in outcrossing plant populations

Genetics Research, 2009

SummaryA linkage–linkage disequilibrium map that describes the pattern and extent of linkage dis-... more SummaryA linkage–linkage disequilibrium map that describes the pattern and extent of linkage dis-equilibrium (LD) decay with genomic distance has now emerged as a viable tool to unravel the genetic structure of population differentiation and fine-map genes for complex traits. The prerequisite for constructing such a map is the simultaneous estimation of the linkage and LD between different loci. Here, we develop a computational algorithm for simultaneously estimating the recombination fraction and LD in a natural outcrossing population with multilocus marker data, which are often estimated separately in most molecular genetic studies. The algorithm is founded on a commonly used progeny test with open-pollinated offspring sampled from a natural population. The information about LD is reflected in the co-segregation of alleles at different loci among parents in the population. Open mating of parents will reveal the genetic linkage of alleles during meiosis. The algorithm was construct...

American Journal of Hypertension

The effects of genistein on the blood pressure of angiotensin-treated hypertensive rats were stud... more The effects of genistein on the blood pressure of angiotensin-treated hypertensive rats were studied in correlation with the ERK-MAPK activity and the production of superoxyde anion radical in the aortic tissue. Hypertension was induced in Sprague-Dawley rats by a treatment of angiotensin II (200ng/kg/hour) with osmotic pumps for a period of 12 days. The genistein (0.17mg/kg/hour) was given following the same procedure. The average arterial pressure was monitored every other day by a tail-cuff method. The superoxyde anion radical concentration was measured by lucegenin-enhanced chemiluminescence technique. The activity of ERK-MAPK pathway was measured by western blot. An increase of arterial pressure of 27% was observed (141.8Ϯ7.49 to 180.6Ϯ2.7mmHg, pϽ0.05) after 12 days in the angiotensin-treated rats compared to controls. When these hypertensive rats were treated with genistein which inhibit tyrosine kinase, the increase in pressure was attenuated to only 9.5%(141.8Ϯ7.49 to 155.3Ϯ1.0mmHg, pϽ0.05). The concentration of the superoxyde anion radical in the aortic tissues of hypertensive rats increased by 235% compared to controls(2360.4Ϯ443 to 7904.5Ϯ883.5cpm, pϽ0.05). When treated with genistein, this increase was lowered to 96%(2360.4Ϯ443 to 4619.5Ϯ224.5cpm, pϽ0.05). Finally, the ERK-MAPK activity was 1.45Ϯ0.12 (pϽ0.05) times greater in tissues from rats treated with angiotensin II alone. The levels of ERK-MAPK activation were similar in tissues from rats treated with genistein and normotensive controls. Our results show that the blockade of tyrosine kinase pathway with genistein can attenuate significantly the increase in blood pressure induced by angiotensin II. It was also shown that the effect of genistein on the increase of blood pressure may be linked to a decrease in the activity of the ERK-MAPK pathway and in the production of the superoxyde anion radical in the aortic tissues. These results suggest a possible implication of ERK-MAPK pathway and superoxyde anion radical modulation in angiotensin-induced hypertension.

Genome-wide analysis of salt-responsive and novel microRNAs in Populus euphratica by deep sequencing

BMC genetics, 2014

Populus euphratica is a representative model woody plant species for studying resistance to abiot... more Populus euphratica is a representative model woody plant species for studying resistance to abiotic stresses such as drought and salt. Salt stress is one of the most common environmental factors that affect plant growth and development. MicroRNAs (miRNAs) are small, noncoding RNAs that have important regulatory functions in plant growth, development, and response to abiotic stress. To investigate the miRNAs involved in the salt-stress response, we constructed four small cDNA libraries from P. euphratica plantlets treated with or without salt (300 mM NaCl, 3 days) in either the root or leaf. Using high-throughput sequencing to identify miRNAs, we found 164 conserved miRNAs belonging to 44 families. Of these, 136 novel miRNAs were from the leaf, and 128 novel miRNAs were from the root. In response to salt stress, 95 miRNAs belonging to 46 conserved miRNAs families changed significantly, with 56 miRNAs upregulated and 39 miRNAs downregulated in the leaf. A comparison of the leaf and ro...

De Novo Assembly and Characterization of the Fruit Transcriptome of Chinese Jujube (Ziziphus jujuba Mill.) Using 454 Pyrosequencing and the Development of Novel Tri-Nucleotide SSR Markers

PLoS ONE, 2014

Current Genomics, 2014

By measuring gene expression at an unprecedented resolution and throughput, RNA-seq has played a ... more By measuring gene expression at an unprecedented resolution and throughput, RNA-seq has played a pivotal role in studying biological functions. Its typical application in clinical medicine is to identify the discrepancies of gene expression between two different types of cancer cells, sensitive and resistant to chemotherapeutic treatment, in a hope to predict drug response. Here we modified and used a mechanistic model to identify distinct patterns of gene expression in response of different types of breast cancer cell lines to chemotherapeutic treatment. This model was founded on a mixture likelihood of Poisson-distributed transcript read data, with each mixture component specified by the Skellam function. By estimating and comparing the amount of gene expression in each environment, the model can test how genes alter their expression in response to environment and how different genes interact with each other in the responsive process. Using the modified model, we identified the alternations of gene expression between two cell lines of breast cancer, resistant and sensitive to tamoxifen, which allows us to interpret the expression mechanism of how genes respond to metabolic differences between the two cell types. The model can have a general implication for studying the plastic pattern of gene expression across different environments measured by RNA-seq.

Journal of Theoretical Biology, 2011

All biological phenomena occurring at different levels of organization from cells to organisms ca... more All biological phenomena occurring at different levels of organization from cells to organisms can be modeled as a dynamic system, in which the underlying components interact dynamically to comprehend its biological function. Such a systems modeling approach facilitates the use of biochemically and biophysically detailed mathematical models to describe and quantify ''living cells,'' leading to an in-depth and precise understanding of the behavior, development and function of a biological system. Here, we illustrate how this approach can be used to map genes or quantitative trait loci (QTLs) that control a complex trait using the example of the circadian rhythm system which has been at the forefront of analytical mathematical modeling for many years. We integrate a system of biologically meaningful delay differential equations (DDEs) into functional mapping, a statistical model designed to map dynamic QTLs involved in biological processes. The DDEs model the ability of circadian rhythm to generate autonomously sustained oscillations with a period close to 24 h, in terms of timevarying mRNA and protein abundances. By incorporating the Runge-Kutta fourth order algorithm within the likelihood-based context of functional mapping, we estimated the genetic parameters that define the periodic pattern of QTL effects on time-varying mRNA and protein abundances and their dynamic association as well as the linkage disequilibrium of the QTL and a marker. We prove theorems about how to choose appropriate parameters to guarantee periodic oscillations. We further used simulation studies to investigate how a QTL influences the period and the amplitude of circadian oscillations through changing model parameters. The model provides a quantitative framework for assessing the interplay between genetic effects of QTLs and rhythmic responses.

A Mechanistic Model for Genetic Machinery of Ontogenetic Growth

Genetics, 2004

Two different genetic mechanisms can be proposed to explain variation in growth trajectories. The... more Two different genetic mechanisms can be proposed to explain variation in growth trajectories. The allelic sensitivity hypothesis states that growth trajectory is controlled by the time-dependent expression of alleles at the deterministic quantitative trait loci (dQTL) formed during embryogenesis. The gene regulation hypothesis states that the differentiation in growth process is due to the opportunistic quantitative trait loci (oQTL) through their mediation with new developmental signals. These two hypotheses of genetic control have been elucidated in the literature. Here, we propose a new statistical model for discerning these two mechanisms in the context of growth trajectories by integrating growth laws within a QTL-mapping framework. This model is developed within the maximum-likelihood context, implemented with a grid approach for estimating the genomic positions of the deterministic and opportunistic QTL and the simplex algorithm for estimating the growth curve parameters of t...

Statistical model for characterizing epistatic control of triploid endosperm triggered by maternal and offspring QTLs

Genetical Research, 2005

To study the effects of maternal and endosperm quantitative trait locus (QTL) interaction on endo... more To study the effects of maternal and endosperm quantitative trait locus (QTL) interaction on endosperm development, we derive a two-stage hierarchical statistical model within the maximum-likelihood context, implemented with an expectation-maximization algorithm. A model incorporating both maternal and offspring marker information can improve the accuracy and precision of genetic mapping. Extensive simulations under different sampling strategies, heritability levels and gene action modes were performed to investigate the statistical properties of the model. The QTL location and parameters are better estimated when two QTLs are located at different intervals than when they are located at the same interval. Also, the additive effect of the offspring QTLs is better estimated than the additive effect of the maternal QTLs. The implications of our model for agricultural and evolutionary genetic research are discussed.

Network Models for Dissecting Plant Development by Functional Mapping

Current Bioinformatics, 2009

BioScience, 2003

Allometric power scaling, ontogenetic growth, and phenotypic plasticity represent three fundament... more Allometric power scaling, ontogenetic growth, and phenotypic plasticity represent three fundamental developmental features for every living organism. To analyze these three features of an organism at the interface between development and evolution, researchers must understand their underlying genetic bases. We have developed a general framework for deciphering the genetic machinery that guides allometric scaling, ontogenetic growth, and environment-dependent plasticity in biological organisms. This approach constitutes a step toward creating a unified view of evolutionary biology and developmental biology ("evo-devo").

Bioinformatics, 2007

Motivation: Genetic interactions or epistasis may play an important role in the genetic etiology ... more Motivation: Genetic interactions or epistasis may play an important role in the genetic etiology of drug response. With the availability of large-scale, high-density single nucleotide polymorphism markers, a great challenge is how to associate haplotype structures and complex drug response through its underlying pharmacodynamic mechanisms. Results: We have derived a general statistical model for detecting an interactive network of DNA sequence variants that encode pharmacodynamic processes based on the haplotype map constructed by single nucleotide polymorphisms. The model was validated by a pharmacogenetic study for two predominant beta-adrenergic receptor (AR) subtypes expressed in the heart, 1AR and 2AR. Haplotypes from these two receptors trigger significant interaction effects on the response of heart rate to different dose levels of dobutamine. This model will have implications for pharmacogenetic and pharmacogenomic research and drug discovery.

BMC genetics, 2014

Mei, Prunus mume Sieb. et Zucc., is an ornamental plant popular in East Asia and, as an important... more Mei, Prunus mume Sieb. et Zucc., is an ornamental plant popular in East Asia and, as an important member of genus Prunus, has played a pivotal role in systematic studies of the Rosaceae. However, the genetic architecture of botanical traits in this species remains elusive. This paper represents the first genome-wide mapping study of quantitative trait loci (QTLs) that affect stem growth and form, leaf morphology and leaf anatomy in an intraspecific cross derived from two different mei cultivars. Genetic mapping based on a high-density linkage map constricted from 120 SSRs and 1,484 SNPs led to the detection of multiple QTLs for each trait, some of which exert pleiotropic effects on correlative traits. Each QTL explains 3-12% of the phenotypic variance. Several leaf size traits were found to share common QTLs, whereas growth-related traits and plant form traits might be controlled by a different set of QTLs. Our findings provide unique insights into the genetic control of tree growth...

Theoretical Population Biology, 2002

Polyploids can be classified as either allopolyploids or autopolyploids based on their presumed o... more Polyploids can be classified as either allopolyploids or autopolyploids based on their presumed origins. From a perspective of linkage analysis, however, the nature of polyploids can be better described as bivalent polyploids, in which two chromosomes pair at meiosis, multivalent polyploids, in which more than two chromosomes pair, and general polyploids, in which bivalent and multivalent formations occur simultaneously. In this paper, we develop a statistical method for linkage analysis of polymorphic markers in bivalent polyploids. This method takes into account a unique cytological pairing mechanism for the formation of diploid gametes in tetraploids}preferential bivalent pairings at meiosis during which two homologous chromosomes pair with a higher probability than two homoeologous chromosomes. The higher frequency of homologous over homoeologous pairing, defined as the preferential pairing factor, affects the segregation patterns and linkage analysis of different genes on the same chromosome. A maximum likelihood method implemented with the EM algorithm is proposed to simultaneously estimate linkage and parental linkage phases over a pair of markers from any possible marker cross type between two outbred bivalent tetraploid parents demonstrating preferential bivalent pairings. Simulation studies display that the method can be well used to estimate the recombination fraction between different marker types and the preferential pairing factor typical of bivalent tetraploids. The implications of this method for current genome projects in polyploid species are discussed.

Theoretical and Applied Genetics, 2011

Quality protein maize (QPM) is a high lysinecontaining corn that is based on genetic modification... more Quality protein maize (QPM) is a high lysinecontaining corn that is based on genetic modification of the opaque2 (o2) mutant. In QPM, modifier genes convert the starchy endosperm of o2 to the vitreous phenotype of wild type maize. There are multiple, unlinked o2 modifier loci (Opm) in QPM and their nature and mode of action are unknown. We previously identified seven Opm QTLs and characterized 16 genes that are differentially up-regulated at a significant level in K0326Y QPM, compared to the starchy endosperm mutant W64Ao2. In order to further characterize these Opm QTLs and the genes up-regulated in K0326Y QPM, we created a population of 314 recombinant inbred lines (RILs) from a cross between K0326Y QPM and W64Ao2. The RILs were characterized for three traits associated with endosperm texture: vitreousness, density and hardness. Genetic linkage analysis of the RIL population confirmed three of the previously identified QTLs associated with o2 endosperm modification in K0326Y QPM. Many of the genes up-regulated in K0326Y QPM showed substantially higher levels of expression in vitreous compared with opaque RILs. These included genes associated with the upstream regulation of the ethylene response pathway, and a gene encoding a regulatory Communicated by C. Schön.

A statistical model for high-resolution mapping of quantitative trait loci determining HIV dynamics

Statistics in Medicine, 2004

Are there specific genes that control the pathogenesis of HIV infection? This question, which is ... more Are there specific genes that control the pathogenesis of HIV infection? This question, which is of fundamental importance in designing personalized strategies of gene therapy to control HIV infection, can be examined by genetic mapping approaches. In this article, we present a new statistical model for unravelling the genetic mechanisms for the dynamic change of HIV that causes AIDS by marker-based linkage disequilibrium (LD) analyses. This new model is the extension of our functional mapping theory to integrate viral load trajectories within a genetic mapping framework. Earlier studies of HIV dynamics have led to various mathematical functions for modelling the kinetic curves of plasma virions and CD4 lymphocytes in HIV patients. Through incorporating these functions into the LD-based mapping procedure, we can identify and map individual quantitative trait loci (or QTL) responsible for viral pathogenesis. We derive a closed-form solution for estimating QTL allele frequency and marker-QTL linkage disequilibrium in the context of EM algorithm and implement the simplex algorithm to estimate the mathematical parameters describing the curve shapes of HIV pathogenesis. We performed different simulation scenarios based on currently used clinical designs in AIDS/HIV research to illustrate the utility and power of our model for genetic mapping of HIV dynamics. The implications of our model for genetic and genomic research into AIDS pathogenesis are discussed.

Candidate gene polymorphisms (BoIFNG, TLR4, SLC11A1) as risk factors for paratuberculosis infection in cattle

Preventive Veterinary Medicine, 2009

The extent and distribution of linkage disequilibrium in a multi-hierarchic outbred canine pedigree

Mammalian Genome, 2003

A disequilibrium model for detecting genetic mutations for cancer

Journal of Theoretical Biology, 2010

A dynamic model for genome-wide association studies

Human Genetics, 2011

A nonlinear mixed-effect mixture model for functional mapping of dynamic traits

Heredity, 2008

An algorithmic model for constructing a linkage and linkage disequilibrium map in outcrossing plant populations

Genetics Research, 2009

SummaryA linkage–linkage disequilibrium map that describes the pattern and extent of linkage dis-... more SummaryA linkage–linkage disequilibrium map that describes the pattern and extent of linkage dis-equilibrium (LD) decay with genomic distance has now emerged as a viable tool to unravel the genetic structure of population differentiation and fine-map genes for complex traits. The prerequisite for constructing such a map is the simultaneous estimation of the linkage and LD between different loci. Here, we develop a computational algorithm for simultaneously estimating the recombination fraction and LD in a natural outcrossing population with multilocus marker data, which are often estimated separately in most molecular genetic studies. The algorithm is founded on a commonly used progeny test with open-pollinated offspring sampled from a natural population. The information about LD is reflected in the co-segregation of alleles at different loci among parents in the population. Open mating of parents will reveal the genetic linkage of alleles during meiosis. The algorithm was construct...