title: Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics.
abstract: Kuru is an acquired prion disease largely restricted to the Fore linguistic group of the Papua New Guinea Highlands, which was transmitted during endocannibalistic feasts. Heterozygosity for a common polymorphism in the human prion protein gene (PRNP) confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly PRNP 129 heterozygotes. Kuru imposed strong balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes. Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.
authors.affiliation: Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
authors.forename: Michael P H
authors.initials: MP
authors.lastname: Stumpf
authors.forename: Jerome
authors.initials: J
authors.lastname: Whitfield
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Beck
authors.forename: Mark
authors.initials: M
authors.lastname: Poulter
authors.forename: Tracy
authors.initials: T
authors.lastname: Campbell
authors.forename: James B
authors.initials: JB
authors.lastname: Uphill
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Michael
authors.initials: M
authors.lastname: Alpers
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.forename: John
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000328:Adult; D000818:Animals; D002190:Cannibalism; D002648:Child; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics; D004196:Disease Outbreaks / Q000266:history*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D049672:History, 19th Century; D049673:History, 20th Century; D049690:History, Ancient; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate; D007729:Kuru / Q000453:epidemiology / Q000235:genetics / Q000266:history* / Q000635:transmission; D015810:Linkage Disequilibrium; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010219:Papua New Guinea / Q000453:epidemiology; D011110:Polymorphism, Genetic; D018621:PrPC Proteins / Q000235:genetics*; D012641:Selection, Genetic; D014633:Valine / Q000235:genetics
chemical_list: D003062:Codon; D018621:PrPC Proteins; D008715:Methionine; D014633:Valine