International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E43 Quantitative Trait Locus Analysis of Prion Disease Incubation Time

S. E. Lloyd, J. A. Beck, E. M. C. Fisher and J. Collinge. MRC Prion Unit, Neurogenetics Department, Imperial College School of Medicine at St Mary's, London, UK

Prion disease incubation time in mice is a quantitative trait varying from 100-500 days. The main genetic determinant of incubation time is Prnp where allele a (Leu 108, Thr 189) and allele b (Phe 108, Val 189) are associated with short and long incubation times respectively. Incubation times within an inbred line of mice are highly reproducible showing less than 5% variation between individual animals. Significant differences in incubation times occur between inbred lines with the same Prnp alleles suggesting that other genes are contributing to the observed variation. Where the mean incubation times differ by more than 2 standard deviations it should be possible to genetically map these loci. In this study we have set up an intercross between NZW and CAST and have inoculated intra-cerebrally approximately 1400 F2 animals with mouse scrapie (Chandler/RML), 400 F2s with mouse passaged BSE and 400 F2s with BSE. We are currently completing whole genome scans on each animal with an average intermarker distance of 10cM. When both phenotype and genotype data are available, QTL analysis will be carried out to identify new loci influencing prion disease incubation time.


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