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Comparison of Haplotype Methods to detect selection

Alexandra I. Vatsiou, Christelle Melodelima, Eric Bazin, Oscar Gaggiotti Laboratoire d'Ecologie Alpine, University Joseph Fourier, Grenoble, France
email: alex.vatsiou @ gmail.com

Haplotype Methods that were compared


Many methods take advantage of the increase of linkage disequilibrium and extent of haplotype homozygocity generated by selection. In this study we will compare five methods that have used this principle to detect selection. Our goal is to test the performance of each method under different scenarios of populations structure and different parameter values (migration, recombination and selection) iHS: Integrated Haplotype Score (1 population) (Voight et al.2007) EHHST: Extended haplotype-based homozygosity score test (1 population) (Zhong et al. 2010) XP-EHH: Cross Population Extended Haplotype Homozygosity (2 populations) (Sabeti et al. 2007) XPCLR: Cross population Composite Likelihood Ratio (2 populations) (Chen et al. 2010) XP-EHHST: Cross-population extended haplotype-based homozygosity score tests (2 populations) (Zhong et al. 2011)

Test of robustness
Population Structure
Stepping Stone Model
Y 2500 X 2500 W 2500

Selection within population Y


Initialize all the loci except locus 50 (monomorphic), sampling from the beta distribution

Hard Sweep Burnin

X 2500

Insert a Mutated Allele at locus 50 within an individual.Set Positive Selection (s=0.1)

Other Parameters Mutation rate: 10-7 Recombination Rate: 0.00375cM/kb No of loci: 101 Biallelic loci: 0 1 Selection model: 00 01 11 1+s 1+s/2 1

Y 2500

Z 2500

OR
W 2500

tbegin
Initialize all the loci, sampling from the beta distribution

Generations

tselection

tend

Island Model
Z 2500

Set Positive Selection (s=0.01)

Soft Sweep

Results (Hard Sweep & Island Model)


Migration Rate 0.05 Migration Rate 0.01

Discussion
Migration affects the power significantly. iHS is the best test to use with high migration but still the FDR > 0.5. EHHST & XP-EHHST DO NOT work well. XP-EHH & XPCLR work as expected.

Selected locus not in the data

XP-EHH is the only test to detect the selected region if the selected locus is not in the data (migration=0.01). All the methods have the same pattern in a Stepping Stone as the Island Model No method worked well for a soft sweep. The analysis is a practical guideline to choose the most appropriate method.

FUTURE:
How the haplotype diversity & length evolves in a soft sweep?

Selected locus not in the data

REFS
1. Chen, H., et al. (2010), ' Population differentiation as a test for selective sweeps.', Genome Research, 20 (3), 393-402. 2. Sabeti, P. C., et al. (2002), 'Detecting recent positive selection in the human genome from haplotype structure', Nature, 419 (6909), 832-7. 3. Sabeti, P. C., et al. (2007), 'Genome-wide detection and characterization of positive selection in human populations', Nature, 449 (7164), 913-8. 4. Voight, B. F., et al. (2006), 'A map of recent positive selection in the human genome', PLoS Biol, 4 (3), 72. 5. Zhong, M., et al. (2010), 'A powerful score test to detect positive selection in genome-wide scans', Eur J Hum Genet, 18 (10), 1148-59. 6. Zhong, M., et al. (2011), ' A cross-population extended haplotypebased homozygosity score test to detect positive selection in genomewide scans', Statistics and Its Interface, 4 (11), 5163.

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