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Fine-mapping the Favored Mutation in a Positive Selective Sweep

View ORCID ProfileAli Akbari, Joseph J. Vitti, View ORCID ProfileArya Iranmehr, View ORCID ProfileMehrdad Bakhtiari, Pardis C. Sabeti, View ORCID ProfileSiavash Mirarab, Vineet Bafna
doi: https://doi.org/10.1101/139055
Ali Akbari
1Department of Electrical & Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA
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Joseph J. Vitti
2Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Arya Iranmehr
1Department of Electrical & Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA
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Mehrdad Bakhtiari
4Department of Computer Science & Engineering, University of California, San Diego, La Jolla, CA 92093, USA
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Pardis C. Sabeti
2Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Siavash Mirarab
1Department of Electrical & Computer Engineering, University of California, San Diego, La Jolla, CA 92093, USA
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Vineet Bafna
4Department of Computer Science & Engineering, University of California, San Diego, La Jolla, CA 92093, USA
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Abstract

Methods to identify signatures of selective sweeps in population genomics data have been actively developed, but mostly do not identify the specific mutation favored by the selective sweep. We present a method, iSAFE, that uses a statistic derived solely from population genetics signals to pinpoint the favored mutation even when the signature of selection extends to 5Mbp. iSAFE was tested extensively on simulated data and in human populations from the 1000 Genomes Project, at 22 loci with previously characterized selective sweeps. For 14 of the 22 loci, iSAFE ranked the previously characterized candidate mutation among the 13 highest scoring (out of ∼ 21, 000 variants). Three loci did not show a strong signal. For the remaining loci, iSAFE identified previously unreported mutations as being favored. In these regions, all of which involve pigmentation related genes, iSAFE identified identical selected mutations in multiple non-African populations suggesting an out-of-Africa onset of selection. The iSAFE software can be downloaded from https://github.com/alek0991/iSAFE.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 01, 2017.
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Fine-mapping the Favored Mutation in a Positive Selective Sweep
Ali Akbari, Joseph J. Vitti, Arya Iranmehr, Mehrdad Bakhtiari, Pardis C. Sabeti, Siavash Mirarab, Vineet Bafna
bioRxiv 139055; doi: https://doi.org/10.1101/139055
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Fine-mapping the Favored Mutation in a Positive Selective Sweep
Ali Akbari, Joseph J. Vitti, Arya Iranmehr, Mehrdad Bakhtiari, Pardis C. Sabeti, Siavash Mirarab, Vineet Bafna
bioRxiv 139055; doi: https://doi.org/10.1101/139055

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