Hbasrq1a^SM/J
QTL Variant Detail

Summary

• QTL variant: Hbasrq1a^SM/J
• Name: habituation of the acoustic startle response QTL 1a; SM/J
• MGI ID: MGI:6149547
• QTL: Hbasrq1a Location: Chr4:71471589-71471589 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: SM/J

Variant description

• Allele Type: QTL

Notes

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

J:178214

In the current study 472 mice from an (LG/J x SM/J)F2 cross and 135 Chev:LG,SM-G34 (F34) advanced intercross lines were used to identify and fine map significant QTL for startle response, prepulse inhibition (PPI) and habituation of the startle response.

F2 mice were tested at approximately 89 days of age and F34 mice were tested at approximately 92 days of age over the course of a 5 month period. The tests consisted of the presentation of 62 trials that were a mixture of the following five types: a pulse alone trial, which consisted of a 40-millisecond 120-dB burst, a no stimulus trial where no stimulus was presented, and three prepulse trials containing a 20-millisecond prepulse that was either 3, 6 or 12 dB above the 70-dB background noise level followed 100 milliseconds later by a 40-millisecond 120-dB pulse.

The response to each trial was recorded for 65 milliseconds after the beginning of the 120-dB stimulus, or at the beginning of the no stimulus trial. The startle response measure (startle) was the average startle amplitude for all of the pulse-alone trials and was expressed in arbitrary units.

F2 genotyping was performed by KBioscience Ltd. using KASPar. One hundred and sixty-two single nucleotide polymorphisms (SNPs), selected from Petkov et al.(2004), were used as markers. QTL analysis of the F2 mice was analyzed using R/qtl. Effects of sex and strain were used as interactive covariates. Genotyping of the F34 mice used a custom-designed Illumina array to obtain more than 3000 SNPs. F2 and AIL data were combined in the analysis using a mixed model.

Table 1:

QTL Asrq7 (acoustic startle response QTL 7) mapped to Chromosome 7 peaking at 64 cM near SNP rs31102161 with a LOD score of 7.02 when sex was used as an interactive covariate in the F2 analysis. The 1.5 support interval spanned from 56 to 72 cM. Asrq7 accounted for 6.62% of trait variance.

In the combined F2 and F34 analysis QTL Asrq7a (acoustic startle response QTL 7a) was identified with a 1.5 LOD support interval reduced by 31% to a location on Chromosome 7 mapping between 54 and 65 cM, peaking at 60 cM near SNP rs31816605 with a LOD score of 6.05.

QTL Asrq8 (acoustic startle response 8) mapped to Chromosome 17 peaking at 8 cM near SNP rs29530504 with a LOD score of 8.19 when sex was used as an interactive covariate in the F2 analysis. The 1.5 support interval spanned from 7 to 15 cM. Asrq8 accounted for 7.68% of trait variance.

In the combined F2 and F34 analysis QTL Asrq8a (acoustic startle response 8a) was identified with a 1.5 LOD support interval reduced by 25% to a location on Chromosome 17 mapping between 8 and 14 cM, peaking at 13 cM near SNP rs29515258 with a LOD score of 7.25.

For the prepulse inhibition test that was 3 db above the 70-dB background noise, QTL Ppiq11 (prepulse inhibition QTL 11) was identified in the F2 analysis mapping to Chromosome 12 with a peak at 45 cM (rs29172545) with a LOD score of 6.70. The 1.5 support interval spanned from 34 to 52 cM. Ppiq11 accounted for 6.33% of trait variance.

In the combined F2 and F34 analysis QTL Ppiq11a (prepulse inhibition QTL 11a) was identified with a 1.5 LOD support interval reduced by 72% to a location on Chromosome 12 mapping between 45 and 50 cM with a peak at 46 cM near SNP rs29219198 with a LOD score of 6.78.

For the prepulse inhibition test that was 6 db above the above the 70-dB background noise:

QTL Ppiq7 (prepulse inhibition QTL 7) mapped to Chromosome 11 peaking at 26 cM near SNP rs26967743 with a LOD score 4.25 spanning a 1.5 support interval from 14 to 40 cM in the F2 analysis. Ppiq7 accounted for 4.06% of trait variance. The integrated analysis of Ppiq7 on Chr 11 did not achieve significance.

QTL Ppiq8 (prepulse inhibition QTL 8) mapped to Chromosome 12 peaking at 45 cM with a LOD score of 7.65 spanning a 1.5 support interval from 11 to 52 cM in the F2 analysis. Ppiq8 accounted for 7.19% of trait variance.

In the combined F2 and F34 analysis QTL Ppiq8a (prepulse inhibition QTL 8a) was identified with a 1.5 LOD support interval reduced by 88% to a location on Chromosome 12 mapping between 41 and 46 cM with a peak at 45 cM with a LOD score of 6.62.

For the prepulse inhibition test that was 12 db above the above the 70-dB background noise:

QTL Ppiq9 (prepulse inhibition QTL 9) mapped to Chromosome 11 peaking at 22 cM with a LOD score of 4.70 spanning a 1.5 support interval from 9 to 35 cM in the F2 analysis. Ppiq9 accounted for 4.48% of trait variance.

In the combined F2 and F34 analysis QTL Ppiq9a (prepulse inhibition QTL 9a) was identified with a 1.5 LOD support interval was reduced by 88% to a location on Chromosome 11 mapping between 39 and 42 cM with a peak at 40 cM near SNP rs26922491 with a LOD score of 5.31.

QTL Ppiq10 (prepulse inhibition QTL 10) mapped to Chromosome 12 peaking at 47 cM with a LOD score of 6.73 spanning a 1.5 support interval from 13 to 56 cM in the F2 analysis. Ppiq9 accounted for 6.73% of trait variance.

In the combined F2 and F34 analysis QTL Ppiq10a (prepulse inhibition QTL 10a) was identified with a 1.5 LOD support interval reduced by 91% to a location on Chromosome 12 mapping between 42 and 46 cM with a peak 44 near SNP rs6349472 cM with a LOD score of 7.82.

QTL Hbasrq1 (habituation of the acoustic startle response QTL 1) mapped to Chromosome 4 peaking at 33 cM near SNP rs27895401 with a LOD score of 4.40 in the F2 analysis. Hbasrq1 accounted for 4.20% of trait variance.

In the combined F2 and F34 analysis QTL Hbasrq1a (habituation of the acoustic startle response QTL 1a) was identified on Chromosome 4 with a 1.5 LOD support interval reduced by 79% to a location between 29 and 35 cM with a peak at 30 cM near SNP rs32621408 with a LOD score of 4.77.

The SM/J allele was associated with lower prepulse inhibition intensities at all prepulse loci, consistent with the lower PPI observed in inbred SM/J mice. The SM/J allele was also associated with less habituation and was apparently inherited in a recessive pattern.

References

• Original: J:178214 Samocha KE, et al., Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines. Genes Brain Behav. 2010 Oct;9(7):759-67
• All: 1 reference(s)