NR AXSP
AU Mead,S.; Webb,T.E.F.; Collinge,J.
TI Age of Onset and Death in Inherited Prion Diseases are Highly Heritable
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.27
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The common polymorphism at codon 129 of the prion protein gene (PRNP) is known to affect prion disease susceptibility and phenotype. Mouse quantitative trait loci (QTL) studies support the existence of multiple modifiers of incubation time unlinked to Prnp but evidence to support the existence of human prion disease modifiers has been lacking. We present the correlation of age at onset or death, expressed as a composite Z score, between first degree relatives in multiple large UK inherited prion disease kindreds. Our analysis suggests that overall heritability of the composite phenotype is
0.54 (95% confidence interval 0.08-0.92). This measure may be an underestimate of the total genetic contribution to phenotypic heterogeneity as the analysis does not incorporate the effect of fixed PRNP mutation-linked modifiers. Although the confidence intervals are wide, these data suggest a significant heritable component to phenotypic variability and support attempts to identify specific human prion disease modifier genes.
AD S. Mead, T.E.F. Webb, J. Collinge, MRC Prion Unit, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: S. Mead, T.E.F. Webb, J. Beck, M. Poulter, J. Uphill, T. Campbell, G. Adamson und J. Collinge)