Systems Mapping: How to Improve the Genetic Mapping of Complex Traits Through Design Principles of Biological Systems

Background: Every phenotypic trait can be viewed as a “system” in which a group of interconnected componentsfunction synergistically to yield a unified whole. Once a system’s components and their interactions have beendelineated according to biological principles, we can manipulate and engineer functionally relevant components toproduce a desirable system phenotype.Results: We describe a conceptual framework for mapping quantitative trait loci (QTLs) that control complex traitsby treating trait formation as a dynamic system. This framework, called systems mapping, incorporates a system ofdifferential equations that quantifies how alterations of different components lead to the global change of traitdevelopment and function through genes, and provides a quantitative and testable platform for assessing theinterplay between gene action and development. We applied systems mapping to analyze biomass growth data ina mapping population of soybeans and identified specific loci that are responsible for the dynamics of biomasspartitioning to leaves, stem, and roots.Conclusions: We show that systems mapping implemented by design principles of biological systems is quiteversatile for deciphering the genetic machineries for size-shape, structural-functional, sink-source and pleiotropicrelationships underlying plant physiology and development. Systems mapping should enable geneticists to shedlight on the genetic complexity of any biological system in plants and other organisms and predict itsphysiological and pathological states

Does China’s Trade Defy Cultural Barriers?

Using annual data for China and 88 trading partners that span the period 1995–2011, we estimate whether cross-societal cultural differences influence China’s external trade flows. Our results, obtained from the estimation of a series of multi-level mixed effect random intercepts and coefficients models, indicate that China’s aggregate exports and imports are largely unaffected by the cultural distance between China and its trading partners. Examination of disaggregate trade measures and consideration of the underlying dimensions of our composite cultural distance variable produces a largely similar result. Taken collectively, our results suggest that China’s trade is less affected by cultural distance than has been reported for other countries in similar studies

Functional mapping of genotype-environment interactions for soybean growth by a semiparametric approach

<p>Abstract</p> <p>Background</p> <p>Functional mapping is a powerful approach for mapping quantitative trait loci (QTLs) that control biological processes. Functional mapping incorporates mathematical aspects of growth and development into a general QTL mapping framework and has been recently integrated with composite interval mapping to build up a so-called composite functional mapping model, aimed to separate multiple linked QTLs on the same chromosomal region.</p> <p>Results</p> <p>This article reports the principle of using composite functional mapping to estimate the effects of QTL-environment interactions on growth trajectories by parametrically modeling the tested QTL in a marker interval and nonparametrically modeling the markers outside the interval as co-factors. With this new model, we can characterize the dynamic patterns of the genetic effects of QTLs governing growth trajectories, estimate the global effects of the underlying QTLs during the course of growth and development, and test the differentiation in the shapes of QTL genotype-specific growth curves between different environments. By analyzing a real example from a soybean genome project, our model detects several QTLs that cause significant genotype-environment interactions for plant height growth processes.</p> <p>Conclusions</p> <p>The model provides a basis for deciphering the genetic architecture of trait expression adjusted to different biotic and abiotic environments for any organism.</p

A Bayesian Framework for Functional Mapping through Joint Modeling of Longitudinal and Time-to-Event Data

The most powerful and comprehensive approach of study in modern biology is to understand the whole process of development and all events of importance to development which occur in the process. As a consequence, joint modeling of developmental processes and events has become one of the most demanding tasks in statistical research. Here, we propose a joint modeling framework for functional mapping of specific quantitative trait loci (QTLs) which controls developmental processes and the timing of development and their causal correlation over time. The joint model contains two submodels, one for a developmental process, known as a longitudinal trait, and the other for a developmental event, known as the time to event, which are connected through a QTL mapping framework. A nonparametric approach is used to model the mean and covariance function of the longitudinal trait while the traditional Cox proportional hazard (PH) model is used to model the event time. The joint model is applied to map QTLs that control whole-plant vegetative biomass growth and time to first flower in soybeans. Results show that this model should be broadly useful for detecting genes controlling physiological and pathological processes and other events of interest in biomedicine

Systems mapping: how to improve the genetic mapping of complex traits through design principles of biological systems

<p>Abstract</p> <p>Background</p> <p>Every phenotypic trait can be viewed as a "system" in which a group of interconnected components function synergistically to yield a unified whole. Once a system's components and their interactions have been delineated according to biological principles, we can manipulate and engineer functionally relevant components to produce a desirable system phenotype.</p> <p>Results</p> <p>We describe a conceptual framework for mapping quantitative trait loci (QTLs) that control complex traits by treating trait formation as a dynamic system. This framework, called systems mapping, incorporates a system of differential equations that quantifies how alterations of different components lead to the global change of trait development and function through genes, and provides a quantitative and testable platform for assessing the interplay between gene action and development. We applied systems mapping to analyze biomass growth data in a mapping population of soybeans and identified specific loci that are responsible for the dynamics of biomass partitioning to leaves, stem, and roots.</p> <p>Conclusions</p> <p>We show that systems mapping implemented by design principles of biological systems is quite versatile for deciphering the genetic machineries for size-shape, structural-functional, sink-source and pleiotropic relationships underlying plant physiology and development. Systems mapping should enable geneticists to shed light on the genetic complexity of any biological system in plants and other organisms and predict its physiological and pathological states.</p

A Conceptual Framework for Mapping Quantitative Trait Loci Regulating Ontogenetic Allometry

Although ontogenetic changes in body shape and its associated allometry has been studied for over a century, essentially nothing is known about their underlying genetic and developmental mechanisms. One of the reasons for this ignorance is the unavailability of a conceptual framework to formulate the experimental design for data collection and statistical models for data analyses. We developed a framework model for unraveling the genetic machinery for ontogenetic changes of allometry. The model incorporates the mathematical aspects of ontogenetic growth and allometry into a maximum likelihood framework for quantitative trait locus (QTL) mapping. As a quantitative platform, the model allows for the testing of a number of biologically meaningful hypotheses to explore the pleiotropic basis of the QTL that regulate ontogeny and allometry. Simulation studies and real data analysis of a live example in soybean have been performed to investigate the statistical behavior of the model and validate its practical utilization. The statistical model proposed will help to study the genetic architecture of complex phenotypes and, therefore, gain better insights into the mechanistic regulation for developmental patterns and processes in organisms