Prdt1^NZW/OlaHsd
QTL Variant Detail

Summary

• QTL variant: Prdt1^NZW/OlaHsd
• Name: prion disease incubation time 1; NZW/OlaHsd
• MGI ID: MGI:2158331
• QTL: Prdt1 Location: Chr2:133077623-133077741 bp Genetic Position: Chr2, cM position of peak correlated region/allele: 65.13 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZW/OlaHsd

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers longer prion incubation time compared to CAST/EiJH. (J:69579)
• Inheritance: Other (see notes)

Notes

Prdt1 exhibits additive inheritance.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:69579

Genome scan at an average resolution of 11 cM was performed on 1,009 (CAST/Ei x NZW/OlaHsd)F2 animals to identify QTLs affecting prion incubation time. The F2 generation was established by intercrossing the F1s in all 4 possible combinations [Table 2]. Parental strain CAST/Ei exhibits a longer prion incubation time compared to NZW/OlaHsd, and (CAST/Ei xNZW/OlaHsd)F1 hybrids exhibit a longer incubation time similar to CAST/Ei. Significant linkage to prion disease incubation time (Prdt) was detected on mouse Chromosomes 2, 11, and 12.

Prdt1 maps to mouse Chromosome 2 from 53 cM - 81 cM with a peak LOD score of 8.2 at D2Mit107. Prdt1 exhibits additive inheritance with CAST/Ei-derived alleles conferring shorter prion incubation time and NZW/OlaHsd-derived alleles conferring longer prion incubation time. Prnp (prion protein) and Prnd (prion protein doublet)map near Prdt1 at 75 cM and are being considered as candidate genes.

Prdt2 maps to mouse Chromosome 2 at 109 cM with a peak LOD score of 4.6 at D2Mit266. Prdt2 exhibits additive inheritance with CAST/Ei-derived alleles conferring increased prion incubation time and NZW/OlaHsd-derived alleles conferring decreased prion incubation time.

Prtd3 maps to mouse Chromosome 11 from 34 cM - 58 cM with a peak LOD score of 57.6 at D11Mit36 and exhibits an additive mode of inheritance. CAST/Ei-derived alleles confer longer prion incubation time and NZW/OlaHsd-derived alleles confer shorter prion incubation time at Prdt3.

Prdt4 maps to mouse Chromosome 12 from 47 cM - 55 cM with a peak LOD score of 6.8 at D12Mit28. CAST/Ei-derived alleles confer longer prion incubation time in a dominant fashion and NZW/OlaHds-derived alleles confer shorter prion incubation time in a recessive fashion at Prdt4. Prpl3 (prion protein ligand 3) may be a candidate gene for Prdt4. Prpl3 has previously been mapped to 51 cM on mouse Chromosome 12 but authors mapped Prpl3 to mouse Chromosome X using a T31 radiation hybrid panel.

J:80787

Linkage analysis was performed on 124 animals from a (NZW/OlaHsd x CAST/Ei)F2 intercross to identify QTLs associated with incubation time for prion disease caused by bovine spongiform encephaly (BSE). Animals were treated intracerebrally with mouse-adapted BSE. Parental strain NZW/OlaHsd exhibits a short incubation period (133 days) whereas parental strain CAST/Ei exhibits a long incubation period (181 days). 144 markers at an average spacing of 11 cM were used in the genome scan. Significant linkage to prion incubation period mapped to mouse Chromosome 2 (LOD=6.34) and mouse Chromosome 11 (LOD=4.77). These loci were identified in a previous study and are named Prdt1 and Prdt3, respectively.

Peak linkage for Prdt1 on chromosome 2 occurred within 1 cM of D2Mit106 (75.6 cM). This locus accounts for 29% of the variance. Animals homozygous for NZW/OlaHsd-derived alleles at Prdt1 exhibit longer mean prion incubation times compared to animals homozygous for CAST/Ei-derived alleles (182 days vs 157 days). Prdt1 exhibits an additive mode of inheritance. Prnp (75 cM) and Prnd (75 cM) map to this interval and are considered possible candidate genes for Prdt1.

Peak linkage for Prdt3 on chromosome 11 occurred within 2 cM of D11Mit124 (57.8 cM). This locus accounts for 13% of the variance. The Prdt3 interval is very broad so it is difficult to pinpoint the location of the QTL. Animals homozygous for CAST/Ei-derived alleles at Prdt3 exhibit longer mean prion incubation times compared to animals homozygous for NZW/OlaHsd-derived alleles. Prdt3 exhibits an additive mode of inheritance. Mapt (64 cM) maps to the Prdt3 interval and is considered a possible candidate gene.

A locus with suggestive linkage mapped to 6.5 cM on mouse Chromosome 14 near D14Mit138.

References

• Original: J:69579 Lloyd SE, et al., Identification of multiple quantitative trait loci linked to prion disease incubation period in mice. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6279-83
• All: 2 reference(s)