A Method for Detecting Recent Selection in the Human Genome From Allele Age Estimates

Corresponding author: Christopher Toomajian, University of Southern California, 835 W. 37th St., SHS 172, Los Angeles, CA 90089-1340., cmtoomaj{at}alumni.uchicago.edu (E-mail)

Communicating editor: W. STEPHAN

Mutations that have recently increased in frequency by positive natural selection are an important component of naturally occurring variation that affects fitness. To identify such variants, we developed a method to test for recent selection by estimating the age of an allele from the extent of haplotype sharing at linked sites. Neutral coalescent simulations are then used to determine the likelihood of this age given the allele's observed frequency. We applied this method to a common disease allele, the hemochromatosis-associated HFE C282Y mutation. Our results allow us to reject neutral models incorporating plausible human demographic histories for HFE C282Y and one other young but common allele, indicating positive selection at HFE or a linked locus. This method will be useful for scanning the human genome for alleles under selection using the haplotype map now being constructed.

This article has been cited by other articles:

				P. Pfaffelhuber, A. Lehnert, and W. Stephan Linkage Disequilibrium Under Genetic Hitchhiking in Finite Populations Genetics, May 1, 2008; 179(1): 527 - 537. [Abstract] [Full Text] [PDF]

				J. F. Storz, M. Baze, J. L. Waite, F. G. Hoffmann, J. C. Opazo, and J. P. Hayes Complex Signatures of Selection and Gene Conversion in the Duplicated Globin Genes of House Mice Genetics, September 1, 2007; 177(1): 481 - 500. [Abstract] [Full Text] [PDF]

				K. Zeng, S. Mano, S. Shi, and C.-I Wu Comparisons of Site- and Haplotype-Frequency Methods for Detecting Positive Selection Mol. Biol. Evol., July 1, 2007; 24(7): 1562 - 1574. [Abstract] [Full Text] [PDF]

				S. Nair, D. Nash, D. Sudimack, A. Jaidee, M. Barends, A.-C. Uhlemann, S. Krishna, F. Nosten, and T. J. C. Anderson Recurrent Gene Amplification and Soft Selective Sweeps during Evolution of Multidrug Resistance in Malaria Parasites Mol. Biol. Evol., February 1, 2007; 24(2): 562 - 573. [Abstract] [Full Text] [PDF]

				P. C. Sabeti, S. F. Schaffner, B. Fry, J. Lohmueller, P. Varilly, O. Shamovsky, A. Palma, T. S. Mikkelsen, D. Altshuler, and E. S. Lander Positive natural selection in the human lineage. Science, June 16, 2006; 312(5780): 1614 - 1620. [Abstract] [Full Text] [PDF]

				D. L. van der A, J. J.M. Marx, D. E. Grobbee, M. H. Kamphuis, N. A. Georgiou, J. H. van Kats-Renaud, W. Breuer, Z. I. Cabantchik, M. Roest, H. A.M. Voorbij, et al. Non-Transferrin-Bound Iron and Risk of Coronary Heart Disease in Postmenopausal Women Circulation, April 25, 2006; 113(16): 1942 - 1949. [Abstract] [Full Text] [PDF]

				P. J Stover Influence of human genetic variation on nutritional requirements Am. J. Clinical Nutrition, February 1, 2006; 83(2): 436S - 442S. [Abstract] [Full Text] [PDF]

				M. A. Saunders, M. Slatkin, C. Garner, M. F. Hammer, and M. W. Nachman The Extent of Linkage Disequilibrium Caused by Selection on G6PD in Humans Genetics, November 1, 2005; 171(3): 1219 - 1229. [Abstract] [Full Text] [PDF]

				E. Beutler Iron absorption in carriers of the C282Y hemochromatosis mutation Am. J. Clinical Nutrition, October 1, 2004; 80(4): 799 - 800. [Full Text] [PDF]

				T. Tsunoda, G. M. Lathrop, A. Sekine, R. Yamada, A. Takahashi, Y. Ohnishi, T. Tanaka, and Y. Nakamura Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome Hum. Mol. Genet., August 1, 2004; 13(15): 1623 - 1632. [Abstract] [Full Text] [PDF]