Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness

Axel M Hillmer, Jan Freudenberg, Sean Myles, Stefan Herms, Kun Tang, David A Hughes, Felix F Brockschmidt, Yijun Ruan, Mark Stoneking, Markus M Nöthen

Research output: Contribution to journalArticle (Academic Journal)

29 Citations (Scopus)

Abstract

Genetic variants in the human androgen receptor gene (AR) are associated with male pattern baldness (androgenetic alopecia, AGA) in Europeans. Previous observations of long-range linkage disequilibrium at the AR locus are consistent with the hypothesis of recent positive selection. Here, we further investigate this signature and its relationship to the AGA risk haplotype. The haplotype homozygosity suggests that the AGA risk haplotype was driven to high frequency by positive selection in Europeans although a low meiotic recombination rate contributed to the high haplotype homozygosity. Further, we find high levels of population differentiation as measured by F(ST) and a series of fixed derived alleles along an extended region centromeric to AR in the Asian HapMap sample. The predominant AGA risk haplotype also carries the putatively functional variant 57K in the flanking ectodysplasin A2 receptor gene (EDA2R). It is therefore probable that the AGA risk haplotype rose to high frequency in combination with this EDA2R variant, possibly by hitchhiking on a positively selected 57K haplotype.

Original languageEnglish
Pages (from-to)255-64
Number of pages10
JournalHuman Genetics
Volume126
Issue number2
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Alleles
  • Alopecia/genetics
  • Ectodysplasins/genetics
  • Gene Frequency
  • Genetic Variation
  • Global Health
  • Haplotypes
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Male
  • Meiosis
  • Promoter Regions, Genetic
  • Receptors, Androgen/genetics
  • Recombination, Genetic

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