Prion susceptibility and protective alleles exhibit marked geographic differences

Hum Mutat. 2003 Jul;22(1):104-5. doi: 10.1002/humu.9157.


A total of 616 chromosomes from control individuals of all major continental groups, and six individuals affected by either Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI), were typed with a new single-reaction protocol method and were also sequenced, with total reproducibility to screen variation at important positions (385A>G: M129V and 655G>A: E219K) in the human prion protein gene (PRNP). We have found, for the first time, that 129V allele is highly represented in some populations from the Americas, and that 129M and 129V are in similar frequencies in Africa. The 129M susceptibility allele was found at high frequencies in Old World populations, very high in the Pacific ( approximately 81%) and up to 93% in Central and East Asia, but at a low frequency (approximately 30%) in Native Americans. The protective 219L allele was restricted to Asian and Pacific populations. Susceptibility alleles exhibit marked geographic differences in frequency, and thus, differences in probability to develop prion diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa / epidemiology
  • Africa South of the Sahara / epidemiology
  • Alleles*
  • Asia / epidemiology
  • Asia, Central / epidemiology
  • Central America / epidemiology
  • Codon / genetics
  • Creutzfeldt-Jakob Syndrome / epidemiology
  • Creutzfeldt-Jakob Syndrome / genetics*
  • Europe / epidemiology
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetics, Population / methods*
  • Humans
  • Insomnia, Fatal Familial / epidemiology
  • Insomnia, Fatal Familial / genetics*
  • North America / epidemiology
  • Pacific Islands / epidemiology
  • Prions / genetics*
  • Prions / pathogenicity*
  • South America / epidemiology


  • Codon
  • Prions