The β-globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria

Elizabeth T. Wood, Daryn A. Stover, Montgomery Slatkin, Michael W. Nachman, Michael F. Hammer

Research output: Contribution to journalArticle

38 Scopus citations


Recombination is expected to reduce the effect of selection on the extent of linkage disequilibrium (LD), but the impact that recombinational hotspots have on sites linked to selected mutations has not been investigated. We empirically determine chromosomal linkage phase for 5.2 kb spanning the β-globin gene and hotspot. We estimate that the HbC mutation, which is positively selected because of malaria, originated <5,000 years ago and that selection coefficients are 0.04-0.09. Despite strong selection and the recent origin of the HbC allele, recombination (crossing-over or gene conversion) is observed within 1 kb 5′ of the selected site on more than one-third of the HbC chromosomes sampled. The rapid decay in LD upstream of the HbC allele demonstrates the large effect the β-globin hotspot has in mitigating the effects of positive selection on linked variation.

Original languageEnglish (US)
Pages (from-to)637-642
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number4
StatePublished - Oct 2005


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this