Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction
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Mike Schmidt
, Elizabeth R Hauser , Eden R. Martin und Silke Schmidt
We have previously distributed a software package, SIMLA (SIMulation of Linkage and Association), which can be used to generate disease phenotype and marker genotype data in three-generational pedigrees of user-specified structure. To our knowledge, SIMLA is the only publicly available program that can simulate variable levels of both linkage (recombination) and linkage disequilibrium (LD) between marker and disease loci in general pedigrees. While the previous SIMLA version provided flexibility in choosing many parameters relevant for linkage and association mapping of complex human diseases, it did not allow for the segregation of more than one disease locus in a given pedigree and did not incorporate environmental covariates possibly interacting with disease susceptibility genes.Here, we present an extension of the simulation algorithm characterized by a much more general penetrance function, which allows for the joint action of up to two genes and up to two environmental covariates in the simulated pedigrees, with all possible multiplicative interaction effects between them. This makes the program even more useful for comparing the performance of different linkage and association analysis methods applied to complex human phenotypes. SIMLA can assist investigators in planning and designing a variety of linkage and association studies, and can help interpret results of real data analyses by comparing them to results obtained under a user-controlled data generation mechanism.A free download of the SIMLA package is available at http://wwwchg.duhs.duke.edu/software.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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Artikel in diesem Heft
- Article
- Estimating Motifs Under Order Restrictions
- Reproducible Research: A Bioinformatics Case Study
- Generalized Rank Tests for Replicated Microarray Data
- Stepwise Normalization of Two-Channel Spotted Microarrays
- Comparing Automatic and Manual Image Processing in FLARE Assay Analysis for Colon Carcinogenesis
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- Early Diagnostic Marker Panel Determination for Microarray Based Clinical Studies
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- Combined Association and Linkage Analysis for General Pedigrees and Genetic Models
- Incorporating Biological Information as a Prior in an Empirical Bayes Approach to Analyzing Microarray Data
- The Relative Inefficiency of Sequence Weights Approaches in Determining a Nucleotide Position Weight Matrix
- A Simple Loglinear Model for Haplotype Effects in a Case-Control Study Involving Two Unphased Genotypes
- Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction
- Error Distribution for Gene Expression Data
- A General Framework for Weighted Gene Co-Expression Network Analysis
- Statistical Inference in Evolutionary Models of DNA Sequences via the EM Algorithm
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- Continuous Covariates in Genetic Association Studies of Case-Parent Triads: Gene and Gene-Environment Interaction Effects, Population Stratification, and Power Analysis
- Robust Remote Homology Detection by Feature Based Profile Hidden Markov Models
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- Hierarchical Inverse Gaussian Models and Multiple Testing: Application to Gene Expression Data
- FADO: A Statistical Method to Detect Favored or Avoided Distances between Occurrences of Motifs using the Hawkes' Model
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- Fold-Change Estimation of Differentially Expressed Genes using Mixture Mixed-Model
- Test on the Structure of Biological Sequences via Chaos Game Representation
- Reverse Engineering Galactose Regulation in Yeast through Model Selection
- Empirical Bayes and Resampling Based Multiple Testing Procedure Controlling Tail Probability of the Proportion of False Positives.
- Weighted Analysis of Paired Microarray Experiments
- A Probabilistic Approach to Large-Scale Association Scans: A Semi-Bayesian Method to Detect Disease-Predisposing Alleles
- A Shrinkage Approach to Large-Scale Covariance Matrix Estimation and Implications for Functional Genomics
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- Computing Asymptotic Power and Sample Size for Case-Control Genetic Association Studies in the Presence of Phenotype and/or Genotype Misclassification Errors