NR AWMN
AU Rodriguez-Martinez,A.B.; Alfonso-Sanchez,M.A.; Pena,J.A.; Zarranz,J.J.; de Pacorbo,M.M.
TI Study of the D178N mutation in Spain: a unique common ancestor?
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions GEN-25
PT Konferenz-Poster
AB
Fatal Familial Insomnia belongs to the group of inherited prion diseases. This neurological disorder is caused by a missense substitution at codon 178 of the PRNP gene and its incidence is very low. However, to date, approximately 50% of the cases registered in Spain, are located in a Northern region (Basque Country). The aim of this work is to study the phylogenetic relationship among D178N mutation carriers in Spain in order to determine whether its distribution is caused by a unique common ancestor or independent mutational events.
The subjects studied were 31 carriers of the D178N mutation (mutated allele associated to methionine allele at codon 129). The variables of the study were six microsatellite markers adjacent to the PRNP gene, comprising a 150kbp length fragment. They were analysed by PCR and fragment analysis. The phylogenetic relationships among the resulting haplotypes were analysed using Network software (v.4.1.1.2.).
Seven haplotypes (H1-H7) associated to the D178N mutation were obtained. Among them, the most frequent haplotype was H5, which was found in 11 individuals, all of them from the Basque Country. The second most frequent haplotype was H3 followed by H1.
The phylogenetic analyses showed, on one side, the agroupation of H6, H7 and H4 haplotypes, and on the other side, the agroupation of H3, H2 and H1 haplotypes. The haplotype H5 was observed to be located far from these two groups. These results suggest that H7 and H4 derive from one haplotype, possibly H6, and that H2 and H1 derive from haplotype H3. The results obtained by the analysis of the microsatellite markers show the existente of 7 haplotypes associated to the D178N mutation in Spain. Nevertheless, the analysis of phylogenetic relationship reduces to three, the differenciated haplotypes. This suggests that the actual distribution of the D178N mutation in Spain may be due to three mutational events, possibly originated in independent moments, or to an ancestral and unique foundational event.
AD A.B. Rodríguez-Martínez: Dpto. Z. y Biología Celular. Facultad de Farmacia. University of the Basque Country, Spain; M.A. Alfonso-Sánchez, J.A. Peña: Dpto. de Genetica y Antropologia Fisica, Facultad de Ciencia y Tecnologia, University of the Basque Country, Spain; J.J. Zarranz: Servicio de Neurología. Hospital de Cruces. Bilbao. Spain; M.M. de Pacorbo: Dpto. Z. y Biología Celular. Facultad de Farmacia. University of the Basque Country. Spain, Servicio de Genómica: Banco de ADN , University of the Basque Country, Spain, Servicio de Genómica: Banco de ADN Facultad de Farmacia, Universidad del País Vasco, Paseo de la Universidad, 7 01006, Vitoria-Gasteiz Spain
SP englisch
PO Italien