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A Composite-Conditional-Likelihood Approach for Gene Mapping Based on Linkage Disequilibrium in Windows of Marker Loci
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Fabrice Larribe
Published/Copyright:
August 30, 2008
A composite-conditional-likelihood (CCL) approach is proposed to map the position of a trait-influencing mutation (TIM) using the ancestral recombination graph (ARG) and importance sampling to reconstruct the genealogy of DNA sequences with respect to windows of marker loci and predict the linkage disequilibrium pattern observed in a sample of cases and controls. The method is designed to fine-map the location of a disease mutation, not as an association study. The CCL function proposed for the position of the TIM is a weighted product of conditional likelihood functions for windows of a given number of marker loci that encompass the TIM locus, given the sample configuration at the marker loci in those windows. A rare recessive allele is assumed for the TIM and single nucleotide polymorphisms (SNPs) are considered as markers. The method is applied to a range of simulated data sets. Not only do the CCL profiles converge more rapidly with smaller window sizes as the number of simulated histories of the sampled sequences increases, but the maximum-likelihood estimates for the position of the TIM remain as satisfactory, while requiring significantly less computing time. The simulations also suggest that non-random samples, more precisely, a non-proportional number of controls versus the number of cases, has little effect on the estimation procedure as well as sample size and marker density beyond some threshold values. Moreover, when compared with some other recent methods under the same assumptions, the CCL approach proves to be competitive.
Keywords: gene mapping; linkage disequilibrium; composite likelihood; conditional likelihood; ancestral recombination graph; importance sampling
Published Online: 2008-8-30
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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Keywords for this article
gene mapping;
linkage disequilibrium;
composite likelihood;
conditional likelihood;
ancestral recombination graph;
importance sampling
Articles in the same Issue
- Article
- Self-Organizing Maps with Statistical Phase Synchronization (SOMPS) for Analyzing Cell Cycle-Specific Gene Expression Data
- Coalescent Time Distributions in Trees of Arbitrary Size
- Quantifying the Association between Gene Expressions and DNA-Markers by Penalized Canonical Correlation Analysis
- Nonparametric Functional Mapping of Quantitative Trait Loci Underlying Programmed Cell Death
- Accommodating Uncertainty in a Tree Set for Function Estimation
- Drifting Markov Models with Polynomial Drift and Applications to DNA Sequences
- Comparing the Characteristics of Gene Expression Profiles Derived by Univariate and Multivariate Classification Methods
- Calculating Confidence Intervals for Prediction Error in Microarray Classification Using Resampling
- Structure Learning in Nested Effects Models
- Correcting the Estimated Level of Differential Expression for Gene Selection Bias: Application to a Microarray Study
- Adapting Prediction Error Estimates for Biased Complexity Selection in High-Dimensional Bootstrap Samples
- Adaptive Choice of the Number of Bootstrap Samples in Large Scale Multiple Testing
- Re-Cracking the Nucleosome Positioning Code
- Semi-Parametric Differential Expression Analysis via Partial Mixture Estimation
- A SNP Streak Model for the Identification of Genetic Regions Identical-by-descent
- Detecting Two-Locus Gene-Gene Effects Using Monotonisation of the Penetrance Matrix
- Modeling DNA Methylation in a Population of Cancer Cells
- Phenotyping Genetic Diseases Using an Extension of µ-Scores for Multivariate Data
- The Estimator of the Optimal Measure of Allelic Association: Mean, Variance and Probability Distribution When the Sample Size Tends to Infinity
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- A Comparison of Normalization Techniques for MicroRNA Microarray Data
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- Approximately Sufficient Statistics and Bayesian Computation
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- Statistical Methods in Integrative Analysis for Gene Regulatory Modules
- Reducing Spatial Flaws in Oligonucleotide Arrays by Using Neighborhood Information
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- A Unification of Multivariate Methods for Meta-Analysis of Genetic Association Studies
- Importance Sampling for the Infinite Sites Model
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- Addressing the Shortcomings of Three Recent Bayesian Methods for Detecting Interspecific Recombination in DNA Sequence Alignments
- A Sparse PLS for Variable Selection when Integrating Omics Data
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