Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation.
Neurogenetics
; 9(2): 109-18, 2008 May.
Article
em En
| MEDLINE
| ID: mdl-18347820
ABSTRACT
This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish patients, whereas ACATTA-M was typical of the German cases. It is interesting to note that both haplotypes were identified in the Italian samples GCATTA-M in a family from the Tuscany region and ACATTA-M in a family from the Veneto region. Our findings suggest the occurrence of two independent D178N-129M mutational events in Europe, preserved and transmitted from one generation to the next until nowadays. Likewise, results based on the analysis of SNP data indicate that previous hypotheses postulating that the D178N mutation had independent origins for each family and that its global distribution was determined by recurrent mutational events must be regarded with caution.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Príons
/
Efeito Fundador
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Mutação de Sentido Incorreto
/
Insônia Familiar Fatal
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Neurogenetics
Assunto da revista:
GENETICA
/
NEUROLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha
País de publicação:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA