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Genomic scans for selective sweeps using SNP data

Genome Research · 2005 · Vol. 15(11) · pp. 1566–1575
Rasmus NielsenScott WilliamsonYuseob KimMelissa J. HubiszAndrew G. ClarkCarlos D. Bustamante

Abstract

Detecting selective sweeps from genomic SNP data is complicated by the intricate ascertainment schemes used to discover SNPs, and by the confounding influence of the underlying complex demographics and varying mutation and recombination rates. Current methods for detecting selective sweeps have little or no robustness to the demographic assumptions and varying recombination rates, and provide no method for correcting for ascertainment biases. Here, we present several new tests aimed at detecting selective sweeps from genomic SNP data. Using extensive simulations, we show that a new parametric test, based on composite likelihood, has a high power to detect selective sweeps and is surprisingly robust to assumptions regarding recombination rates and demography (i.e., has low Type I error). Our new test also provides estimates of the location of the selective sweep(s) and the magnitude of the selection coefficient. To illustrate the method, we apply our approach to data from the Seattle SNP project and to Chromosome 2 data from the HapMap project. In Chromosome 2, the most extreme signal is found in the lactase gene, which previously has been shown to be undergoing positive selection. Evidence for selective sweeps is also found in many other regions, including genes known to be associated with disease risk such as DPP10 and COL4A3.

RNA and protein synthesis mechanismsDigestive system and related healthGenetic Associations and EpidemiologyBiologyInternational HapMap ProjectFalse discovery rateSNPBackground selectionGeneticsSingle-nucleotide polymorphismImputation (statistics)Computational biologyStatistics

MeSH terms

Black or African AmericanComputer SimulationHaplotypesHumansModels, GeneticSelection, GeneticGenome, HumanPolymorphism, Single NucleotideGenomicsWhite People

Funding

  • National Science Foundation
  • National Institutes of Health
  • National Institute of General Medical Sciences
  • Division of Environmental Biology
Citations
1,123
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References
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Genetics · 1989 · 1,153 citations
A New Statistical Method for Haplotype Reconstruction from Population Data
The American Journal of Human Genetics · 2001 · 7,519 citations
Hitchhiking Under Positive Darwinian Selection
Genetics · 2000 · 1,904 citations
Genetic Signatures of Strong Recent Positive Selection at the Lactase Gene
The American Journal of Human Genetics · 2004 · 1,182 citations
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