Ahl9^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ahl9^C57BL/6J
• Name: age related hearing loss 9; C57BL/6J
• MGI ID: MGI:5824066
• QTL: Ahl9 Location: unknown Genetic Position: Chr18, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:203332

The authors used C57BL/6J mice, DBA/2J mice, and 33 BXD lines to investigate genetic contributions to high-frequency heaing loss. Hearing level thresholds were longitudinally assessed at either 2 or 3 weeks of age to minimize the burden of anesthesia at a very young age and subsequently at 4, 6, and 12 weeks of age under ketamine/xylazine anesthesia (60/10mg/kg i.p.) in both male and female mice. The average number of mice per strain was 7 (range 2-13).

The auditory brainstem response (ABR) was used to obtain hearing level thresholds. Briefly, hearing level thresholds were measured in response to 1 millisecond tone pips at 4, 8, 16 and 32kHz at intensities ranging from -10 to 110 dB sound pressure level (SPL) at 5 dB resolution. At each sound intensity tested, 600 brainstem evoked responses with artifacts below 30uV were averaged; the minimum threshold was defined as the lowest SPL at which a reproducible peak could be identified. If no response was elicited at 110 dB, the threshold was classified as 115 dB.

Linkage mapping of maximum hearing loss (MHL) values of BXD plus parental strains to genotypes was performed by WebOTL (http://www.genenetwork.org/) scripts, which uses a set of 3,795 SNP and microsatellite markers (NCBI Build 37).

The hearing of a total number of 35 (including parental) strains was evaluated in longitudinal recordings from a postnatal age of either 2 or 3 weeks up to the last measurement at 12 weeks of age. Maximum hearing loss varied greatly among strains and frequencies.

The authors found a novel QTL at Chromosome 18, called Ahl9 (high-frequency hearing loss 9), which is significant at 4 kHz (LRS = 20.9; LOD = 4.53). Peak and/or flanking markers for Ahl9's genomic location were not given.

The authors also confirmed a significant, high-frequency QTL on Chromosome 11, called Ahl8 (Johnson ef al. 2008), for which a mutation in fascin-2 (Fscn2) is responsible (Shin etal. 2010). In MGI, the Ahl8 marker has been withdrawn and is now represented as a known allele of Fscn2.

In the current study, the Ahl8 locus was only significant at 16 kHz (LRS = 20.3 at 16 kHz) and produced peaks of smaller magnitude for 8 and 4 kHz (LRS = 11.7 and 7.6, respectively). The authors report that the Ahl9 locus could explain 39.1% of the variance in MHL at 4 kHz that remained after accounting for the effects of Fscn2.

Both the Ahl8 and Ahl9 QTL are determined by the presence of the DBA/2J allele.

References

• Original: J:203332 Nagtegaal AP, et al., A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strains. Genes Brain Behav. 2012 Nov;11(8):911-20
• All: 1 reference(s)