title: Prion susceptibility and protective alleles exhibit marked geographic differences.
abstract: 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.
authors.affiliation: Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Soldevila
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
authors.forename: Aida M
authors.initials: AM
authors.lastname: Andrés
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Kári
authors.initials: K
authors.lastname: Stefánsson
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
mesh_terms: D000349:Africa / Q000453:epidemiology; D017954:Africa South of the Sahara / Q000453:epidemiology; D000483:Alleles; D001208:Asia / Q000453:epidemiology; D001209:Asia, Central / Q000453:epidemiology; D002489:Central America / Q000453:epidemiology; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005828:Genetics, Population / Q000379:methods*; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000453:epidemiology / Q000235:genetics*; D009656:North America / Q000453:epidemiology; D010139:Pacific Islands / Q000453:epidemiology; D011328:Prions / Q000235:genetics* / Q000472:pathogenicity*; D013020:South America / Q000453:epidemiology
chemical_list: D003062:Codon; D011328:Prions