title: Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.
abstract: With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations.
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143 jeff.wall@ucsf.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Wall
authors.affiliation: Institute for Human Genetics, University of California, San Francisco, California 94143 Department of Biological Sciences, Auburn University, Alabama 36849.
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Stevison
mesh_terms: D001499:Bayes Theorem; D003198:Computer Simulation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
keywords: composite likelihood; linkage disequilibrium; recombination hotspots