Sequential Quantitative Trait Locus Mapping in Experimental Crosses
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Jaya M Satagopan
The etiology of complex diseases is heterogeneous. The presence of risk alleles in one or more genetic loci affects the function of a variety of intermediate biological pathways, resulting in the overt expression of disease. Hence, there is an increasing focus on identifying the genetic basis of disease by systematically studying phenotypic traits pertaining to the underlying biological functions. In this paper we focus on identifying genetic loci linked to quantitative phenotypic traits in experimental crosses. Such genetic mapping methods often use a one stage design by genotyping all the markers of interest on the available subjects. A genome scan based on single locus or multi-locus models is used to identify the putative loci. Since the number of quantitative trait loci (QTLs) is very likely to be small relative to the number of markers genotyped, a one-stage selective genotyping approach is commonly used to reduce the genotyping burden, whereby markers are genotyped solely on individuals with extreme trait values. This approach is powerful in the presence of a single quantitative trait locus (QTL) but may result in substantial loss of information in the presence of multiple QTLs. Here we investigate the efficiency of sequential two stage designs to identify QTLs in experimental populations. Our investigations for backcross and F2 crosses suggest that genotyping all the markers on 60% of the subjects in Stage 1 and genotyping the chromosomes significant at 20% level using additional subjects in Stage 2 and testing using all the subjects provides an efficient approach to identify the QTLs and utilizes only 70% of the genotyping burden relative to a one stage design, regardless of the heritability and genotyping density. Complex traits are a consequence of multiple QTLs conferring main effects as well as epistatic interactions. We propose a two-stage analytic approach where a single-locus genome scan is conducted in Stage 1 to identify promising chromosomes, and interactions are examined using the loci on these chromosomes in Stage 2. We examine settings under which the two-stage analytic approach provides sufficient power to detect the putative QTLs.
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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Articles in the same Issue
- Article
- Accounting for Dependence in Similarity Data from DNA Fingerprinting
- Normalization of Dye Bias in Microarray Data Using the Mixture of Splines Model
- A Generalized Sidak-Holm Procedure and Control of Generalized Error Rates under Independence
- Using Duplicate Genotyped Data in Genetic Analyses: Testing Association and Estimating Error Rates
- Likelihood-Based Inference for Multi-Color Optical Mapping
- Sparse Logistic Regression with Lp Penalty for Biomarker Identification
- Super Learning: An Application to the Prediction of HIV-1 Drug Resistance
- Supervised Detection of Conserved Motifs in DNA Sequences with Cosmo
- Accurate Ranking of Differentially Expressed Genes by a Distribution-Free Shrinkage Approach
- Statistical Inference for Quantitative Polymerase Chain Reaction Using a Hidden Markov Model: A Bayesian Approach
- A Bayesian Model of AFLP Marker Evolution and Phylogenetic Inference
- Sequential Quantitative Trait Locus Mapping in Experimental Crosses
- Case-Control Inference of Interaction between Genetic and Nongenetic Risk Factors under Assumptions on Their Distribution
- Inference on the Limiting False Discovery Rate and the P-value Threshold Parameter Assuming Weak Dependence between Gene Expression Levels within Subject
- Reconstructing Gene Regulatory Networks with Bayesian Networks by Combining Expression Data with Multiple Sources of Prior Knowledge
- Cox Survival Analysis of Microarray Gene Expression Data Using Correlation Principal Component Regression
- A Method for Meta-Analysis of Case-Control Genetic Association Studies Using Logistic Regression
- Approximating the Variance of the Conditional Probability of the State of a Hidden Markov Model
- Using Linear Mixed Models for Normalization of cDNA Microarrays
- Experimental Design for Two-Color Microarrays Applied in a Pre-Existing Split-Plot Experiment
- The Cyclohedron Test for Finding Periodic Genes in Time Course Expression Studies
- H-Tuple Approach to Evaluate Statistical Significance of Biological Sequence Comparison with Gaps
- Multiple Testing Issues in Discriminating Compound-Related Peaks and Chromatograms from High Frequency Noise, Spikes and Solvent-Based Noise in LC - MS Data Sets
- A Bayesian Approach to Estimation and Testing in Time-course Microarray Experiments
- Super Learner
- Testing for Trends in Dose-Response Microarray Experiments: A Comparison of Several Testing Procedures, Multiplicity and Resampling-Based Inference
- On the Operational Characteristics of the Benjamini and Hochberg False Discovery Rate Procedure
- A Comparison of Methods to Control Type I Errors in Microarray Studies
- Selection of Biologically Relevant Genes with a Wrapper Stochastic Algorithm
- T-BAPS: A Bayesian Statistical Tool for Comparison of Microbial Communities Using Terminal-restriction Fragment Length Polymorphism (T-RFLP) Data
- Population Structure and Covariate Analysis Based on Pairwise Microsatellite Allele Matching Frequencies
- Estimating the Arm-Wise False Discovery Rate in Array Comparative Genomic Hybridization Experiments
- An Expectation Maximization Approach to Estimate Malaria Haplotype Frequencies in Multiply Infected Children
- Estimation of Expression Levels in Spotted Microarrays with Saturated Pixels
- Improving Divergence Time Estimation in Phylogenetics: More Taxa vs. Longer Sequences
- Fully Bayesian Mixture Model for Differential Gene Expression: Simulations and Model Checks
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