Modeling Haplotype-Haplotype Interactions in Case-Control Genetic Association Studies

Haplotype analysis has been increasingly used to study the genetic basis of human diseases, but models for characterizing genetic interactions between haplotypes from different chromosomal regions have not been well developed in the current literature. In this article, we describe a statistical model for testing haplotype-haplotype interactions for human diseases with a case-control genetic association design. The model is formulated on a contingency table in which cases and controls are typed for the same set of molecular markers. By integrating well-established quantitative genetic principles, the model is equipped with a capacity to characterize physiologically meaningful epistasis arising from interactions between haplotypes from different chromosomal regions. The model allows the partition of epistasis into different components due to additive × additive, additive × dominance, dominance × additive, and dominance × dominance interactions. We derive the EM algorithm to estimate and test the effects of each of these components on differences in the pattern of genetic variation between cases and controls and, therefore, examine their role in the pathogenesis of human diseases. The method was further extended to investigate gene-environment interactions expressed at the haplotype level. The statistical properties of the models were investigated through simulation studies and its usefulness and utilization validated by analyzing the genetic association of sarcoidosis from a human genetics project

FEATURES OF DESIGN OF TIED-ARCH BRIDGES WITH FLEXIBLE INCLINED SUSPENSION HANGERS

Purpose. Investigation and analysis of the hanger arrangement and the structural stability of a Network arch bridge – a tied-arch bridge with inclined hangers that cross each other at least twice. It is also necessary to make a comparative analysis with other types of hanger arrangements. Methodology. The authors in their research investigated a large number of parameters to determine their influence in the force distribution in the arch. Eventually they determined optimal values for all parameters. These optimal values allowed developing a design guide that leads to optimal arch design. When solving this problem, the authors used three-dimensional finite element models and the objective was to determine the most suitable solution for a road bridge, with a span of 100 meters, consisting of two inclined steel arches, located on a road with two traffic lanes, subjected to medium traffic. The virtual prototype of the model is performed by finite element simulator Midas Civil. Findings. In this study, for the bridge deck, a concrete tie appears to be the best solution considering the structural behavior of network arches, but economic advantages caused by easier erection may lead to steel or a composite bridge deck as better alternatives. Design requirements and local conditions of each particular bridge project will decide the most economic deck design.Originality. To ensure passenger comfort and the stability and continuity of the track, deformations of bridges are constricted. A network arch is a stiff structure with small deflections and therefore suitable to comply with such demands even for high speed railway traffic. A network arch bridge with a concrete tie usually saves more than half the steel required for tied arches with vertical hangers and concrete ties. Practical value. Following the study design advice given in this article leads to savings of about 60 % of structural steel compared with conventional tied arch bridges with vertical hangers

A Drive to Driven Model of Mapping Intraspecific Interaction Networks.

Community ecology theory suggests that an individual\u27s phenotype is determined by the phenotypes of its coexisting members to the extent at which this process can shape community evolution. Here, we develop a mapping theory to identify interaction quantitative trait loci (QTL) governing inter-individual dependence. We mathematically formulate the decision-making strategy of interacting individuals. We integrate these mathematical descriptors into a statistical procedure, enabling the joint characterization of how QTL drive the strengths of ecological interactions and how the genetic architecture of QTL is driven by ecological networks. In three fish full-sib mapping experiments, we identify a set of genome-wide QTL that control a range of societal behaviors, including mutualism, altruism, aggression, and antagonism, and find that these intraspecific interactions increase the genetic variation of body mass by about 50%. We showcase how the interaction QTL can be used as editors to reconstruct and engineer new social networks for ecological communities

Research on the corrosion/permeability/forest resistance of concrete by experimental and microscopic mechanisms under different water-binder ratios

To study the influence of different water–binder ratios on the corrosion, permeability, and freezing properties of concrete, we produced different strengths of concrete with respective water–binder ratios of 0.32, 0.38, 0.50, and 0.66. The corrosion resistance of the concrete was studied via three corrosion methods: full immersion, half immersion, and dry and wet cycles. The impermeability and frost resistance of concrete with different water–binder ratios were tested and analyzed. The test results show that the corrosion modes in order from strong to weak were dry and wet cycles, half soaking, and full soaking. The relative dynamic elasticity modulus and freeze–thaw index were used to evaluate the frost resistance of concrete based on the analysis of three indices of frost resistance. To study the internal mechanism of corrosion of concrete with different water–binder ratios, microscopic pore structure testing of the concrete was conducted using a Micromeritics AutoPore IV 9500 Series instrument. The porosimeter studies show that the smaller the water–binder ratio, the more small pores and the denser the concrete. The smaller the water–binder ratio, the higher the strength and the better the corrosion, permeability, and frost resistance

Methodological implementation of mixed linear models in multi-locus genome-wide association studies

The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS

Phylogenetic Reconstruction and DNA Barcoding for Closely Related Pine Moth Species (Dendrolimus) in China with Multiple Gene Markers

Unlike distinct species, closely related species offer a great challenge for phylogeny reconstruction and species identification with DNA barcoding due to their often overlapping genetic variation. We tested a sibling species group of pine moth pests in China with a standard cytochrome c oxidase subunit I (COI) gene and two alternative internal transcribed spacer (ITS) genes (ITS1 and ITS2). Five different phylogenetic/DNA barcoding analysis methods (Maximum likelihood (ML)/Neighbor-joining (NJ), “best close match” (BCM), Minimum distance (MD), and BP-based method (BP)), representing commonly used methodology (tree-based and non-tree based) in the field, were applied to both single-gene and multiple-gene analyses. Our results demonstrated clear reciprocal species monophyly for three relatively distant related species, Dendrolimus superans, D. houi, D. kikuchii, as recovered by both single and multiple genes while the phylogenetic relationship of three closely related species, D. punctatus, D. tabulaeformis, D. spectabilis, could not be resolved with the traditional tree-building methods. Additionally, we find the standard COI barcode outperforms two nuclear ITS genes, whatever the methods used. On average, the COI barcode achieved a success rate of 94.10–97.40%, while ITS1 and ITS2 obtained a success rate of 64.70–81.60%, indicating ITS genes are less suitable for species identification in this case. We propose the use of an overall success rate of species identification that takes both sequencing success and assignation success into account, since species identification success rates with multiple-gene barcoding system were generally overestimated, especially by tree-based methods, where only successfully sequenced DNA sequences were used to construct a phylogenetic tree. Non-tree based methods, such as MD, BCM, and BP approaches, presented advantages over tree-based methods by reporting the overall success rates with statistical significance. In addition, our results indicate that the most closely related species D. punctatus, D. tabulaeformis, and D. spectabilis, may be still in the process of incomplete lineage sorting, with occasional hybridizations occurring among them

A General Model for Multilocus Epistatic Interactions in Case-Control Studies

Background: Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology: We develop a general model for testing high-order epistatic interactions for a complex disease in a casecontrol study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions: Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis