1. Detection of the footprint of natural selection in the genome
Josefa Domenech Cabrera

2. Methods to detect natural selection

3. Methods to detect natural selection

4. SOLUTION: Cross-Population Extended Haplotype Homozygosity (XP-EHH)
Analysis of HapMap
An allele under positive selection may rise to high frequency rapidly enough that long-range association with nerby polimorphisms will not have time to be eliminated by recombination
Long-Range Haplotype (LRH)
Integrated Haplotype Score (iHS)
DISADGVANTAGE: Only local variation is taken into account to calculate recombination rates
SOLUTION: Cross-Population Extended Haplotype Homozygosity (XP-EHH)

5. Analysis of HapMap
More than 300 candidate regions to have been positive selected where found applying the LRH, iHS and XP-EHH methods
A simulation was done in order to see the neutral evolution of a 10 Gb sequence
22 of the 300 events were not found in the simulated neutral evolution
CHALLENGE: sift through genetic variation in those 22 candidate regions to identify the variants which were targets of selection

6. They looked for alleles common in populations under selection
Analysis of HapMap
CRITERIA APPLIED:
They focused on newly arisen alleles identified by comparison to primate outgroups
They looked for alleles common in populations under selection
They focused on non-synonymous coding SNPs and SNPs in evolutionary conserved sequences

7. Analysis of HapMap
Non-synonymous coding SNPs with highly differentiated high-frequency alleles:
European sample: genes involved in skin pigment differences among humans
Gene SLC24A5: SLC24A5AIIIT polymorphism selected in Europe
Gene SLC45A2: L375F polymorphism selected in Europe

8. Analysis of HapMap
African sample: genes with biologicals links to the Lassa fever virus
Gene LARGE: glycosylase that modifies post-transcriptionally α-dystroglycan
Gene DMD: cytosolic adaptor protein that binds to α-dystroglycan

9. Analysis of HapMap
Asian sample: genes involved in the ectodysplasin (EDA) pathway
Gene EDAR: encodes the receptor for the ligand EDA A1
Polymorphism V370A is near fixation in Asia
Gene EDA2R: encodes the receptor for the ligand EDA A2
Polymorphism R57K is fixed in Asia

10. Bibliography
Detecting Natural Selection in Genomic Data. Joseph J. Vitti, Sharon R. Grossman, and Pardis C. Sabeti.
Genome-wide detection and characterization of positive selection in human populations. Pardis C. Sabeti, Patrick Varilly, Ben Fry, Jason Lohmueller, Elizabeth Hostetter, Chris Cotsapas, Xiaohui Xie, Elizabeth H. Byrne, Steven A. McCarroll, Rachelle Gaudet, Stephen F. Schaffner, Eric S. Lander and The International HapMap Consortium
National Human Genome Research Institute - International HapMap Project. (
SNPedia (
Centers for Disease Control and Prevention (