Calibrating a coalescent simulation of human genome sequence variation
Top Cited Papers
Open Access
- 26 October 2005
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 15 (11), 1576-1583
- https://doi.org/10.1101/gr.3709305
Abstract
Population genetic models play an important role in human genetic research, connecting empirical observations about sequence variation with hypotheses about underlying historical and biological causes. More specifically, models are used to compare empirical measures of sequence variation, linkage disequilibrium (LD), and selection to expectations under a “null” distribution. In the absence of detailed information about human demographic history, and about variation in mutation and recombination rates, simulations have of necessity used arbitrary models, usually simple ones. With the advent of large empirical data sets, it is now possible to calibrate population genetic models with genome-wide data, permitting for the first time the generation of data that are consistent with empirical data across a wide range of characteristics. We present here the first such calibrated model and show that, while still arbitrary, it successfully generates simulated data (for three populations) that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation. No assertion is made about the accuracy of the proposed historical and recombination model, but its ability to generate realistic data meets a long-standing need among geneticists. We anticipate that this model, for which software is publicly available, and others like it will have numerous applications in empirical studies of human genetics.Keywords
This publication has 30 references indexed in Scilit:
- Population History and Natural Selection Shape Patterns of Genetic Variation in 132 GenesPLoS Biology, 2004
- Evidence for substantial fine-scale variation in recombination rates across the human genomeNature Genetics, 2004
- Population-Genetic Basis of Haplotype Blocks in the 5q31 RegionAmerican Journal of Human Genetics, 2004
- Recombination hotspots rather than population history dominate linkage disequilibrium in the MHC class II regionHuman Molecular Genetics, 2003
- Detecting recent positive selection in the human genome from haplotype structureNature, 2002
- Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOXNature Genetics, 2002
- A high-resolution recombination map of the human genomeNature Genetics, 2002
- Patterns of linkage disequilibrium in the human genomeNature Reviews Genetics, 2002
- The Discovery of Single-Nucleotide Polymorphisms—and Inferences about Human Demographic HistoryAmerican Journal of Human Genetics, 2001
- A map of human genome sequence variation containing 1.42 million single nucleotide polymorphismsNature, 2001