Ancestral origins of the prion protein gene D178N mutation in the Basque Country.
Hum Genet. 2005-04-02; 117(1): 61-69
DOI: 10.1007/s00439-005-1277-0
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1. Hum Genet. 2005 Jun;117(1):61-9. Epub 2005 Apr 2.
Ancestral origins of the prion protein gene D178N mutation in the Basque Country.
Rodríguez-Martínez AB(1), Barreau C, Coupry I, Yagüe J, Sánchez-Valle R,
Galdós-Alcelay L, Ibáñez A, Digón A, Fernández-Manchola I, Goizet C, Castro A,
Cuevas N, Alvarez-Alvarez M, de Pancorbo MM, Arveiler B, Zarranz JJ.
Author information:
(1)Unidad de Genómica: Banco de ADN y Genotipado, Facultad de Farmacia,
Universidad del País Vasco, Vitoria-Gasteiz, Spain.
Fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD) are
familial prion diseases with autosomal dominant inheritance of the D178N
mutation. FFI has been reported in at least 27 pedigrees around the world. Twelve
apparently unrelated FFI and fCJD pedigrees with the characteristic D178N
mutation have been reported in the Prion Diseases Registry of the Basque Country
since 1993. The high incidence of familial prion diseases in this region may
reflect a unique ancestral origin of the chromosome carrying this mutation. In
order to investigate this putative founder effect, we developed “happy typing”, a
new approach to the happy mapping method, which consists of the physical
isolation of large haploid genomic DNA fragments and their analysis by the
Polymerase Chain Reaction in order to perform haplotypic analysis instead of
pedigree analysis. Six novel microsatellite markers, located in a 150-kb genomic
segment flanking the PRNP gene were characterized for typing haploid DNA
fragments of 285 kb in size. A common haplotype was found in patients from the
Basque region, strongly suggesting a founder effect. We propose that “happy
typing” constitutes an efficient method for determining disease-associated
haplotypes, since the analysis of a single affected individual per pedigree
should provide sufficient evidence.
DOI: 10.1007/s00439-005-1277-0
PMID: 15806397 [Indexed for MEDLINE]