Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  19
• Reference
  J:146813 Lloyd SE, et al., HECTD2 is associated with susceptibility to mouse and human prion disease. PLoS Genet. 2009 Feb;5(2):e1000383
• ID
  MGI:3843454

Genes

Gene	Assay Type
Prdt5	resistance/susceptibility
D19Mit63	PCR amplified length variant
D19Mit65	PCR amplified length variant

Notes

• Experiment
  A genetic locus on mouse Chromosome 19 displaying association with prion disease susceptibility was confirmed and refined using Northport heterogeneous stock animals derived from semi-randomly mated parental inbred strains A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J and LP/J. One thousand Northport animals were inoculated with mouse-adapted scrapie prions and 400 mice representing the lowest and highest prion incubation times were selected for genotype analysis. Mouse chromosome 19 was targetedfor analysis due to orthology to a prion susceptibility locus on human Chromosome 10. Nine polymorphic markers spaced approximately 1 cM apart were genotyped for mouse Chromosome 19.
  
  Peak linkage to prion incubation time mapped to a 2.9 Mb interval between D19Mit63 (24 cM) and D19Mit65 (26 cM). This locus explains 6.9% of the prion incubation time variance and is named Prdt5 (prion disease incubation time 5). Twenty-seven genes are located within the Prdt5 region. Analysis of SNPs, simple repeats and insertion/deletion polymorphisms led to six potential candidate genes: Hectd2, Exoc6 (26 cM), Cyp26c1, Cyp26a1, Plce1 and Lgi1.
  
  Authors noted Hectd2 displays highly significant SNPs in the 3' UTR region and predicted promoter. Expression analysis of Hectd2 mRNA in brain of 8 week old animals revealed a strain distribution pattern among the Northport parental strains. Group A animals (A/J, AKR/J and BALB/cJ) expressed 2.4-fold higher Hectd2 brain mRNA compared to Group B animals (C3H/HeJ, C57BL/6J, CBA/J and DBA/2J). Higher Hectd2 expression was associated with shorter prion disease incubation time. In addition, C57BL/6J animals with end-stage prion disease displayed five times higher Hectd2 mRNA expression compared to non-diseased C57BL/6J animals.
  
  Analysis of human HECTD2 haplotypes revealed linkage disequilibrium to human prion diseases susceptibility, namely susceptibility to kuru (in Papua New Guinea) and Creutzfeldt - Jacob disease (in the United Kingdom)