XP-EHH

XP-EHH computes cross-population extended haplotype homozygosity to detect loci subject to recent positive selection between populations.

Key Features:

• Long-Range Haplotype Analysis: Uses long-range haplotype methods to detect extended regions of homozygosity indicative of recent selective sweeps.
• Cross-Population Comparisons: Performs cross-population comparisons to identify alleles that have reached near-fixation in one population relative to another.
• Comprehensive Data Analysis: Analyzes over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2).
• Heuristic Development: Applies a heuristic approach to further scrutinize the most significant candidate regions.
• Identification of Non-Synonymous SNPs: Identifies non-synonymous coding single nucleotide polymorphisms (SNPs) that show regional evidence of positive selection.

Scientific Applications:

• Detection of Positive Selection: Identifies genomic regions and specific alleles that have been subject to positive selection across different human populations.
• Biological Process Insights: Highlights co-selection of genes involved in common processes, for example LARGE and DMD related to Lassa virus infection resistance in West Africa; SLC24A5 and SLC45A2 associated with skin pigmentation in Europe; and EDAR and EDA2R involved in hair follicle development in Asia.

Methodology:

Computes cross-population extended haplotype homozygosity using long-range haplotype methods on dense polymorphism data (>3 million sites from HapMap2), performs cross-population comparisons, applies heuristics to top candidate regions, and flags non-synonymous coding SNPs showing regional signals.