Lfnq4^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Lfnq4^C3H/HeJ
• Name: lung function QTL 4; C3H/HeJ
• MGI ID: MGI:3773342
• QTL: Lfnq4 Location: Chr17:11206484-39364059 bp Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL

Notes

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

J:131210

Genetic loci involved in lung function phenotypes were mapped using 150 female animals from a (C3H/HeJ x JF1/MsIeg) x C3H/HeJ backcross and 150 females from a (C3H/HeJ x JF1/MsIeg)F2 intercross. Linkage analysis was performed using 140 polymorphic markers ata 10.5 cM resolution. An additional 70 microsatellite markers were used for fine mapping potential QTLs. All animals were analyzed at 12-14 weeks of age for the following phenotypes: total lung capacity (TLC), dead space volume (VD), lung compliance (CL),and diffusing capacity (DCO). Parental strain C3H/HeJ displays higher total lung capacity and increased values for other lung function phenotypes compared to parental strain JF1/MsIeg.

Significant linkage to VD mapped to 34 cM on mouse Chromosome 5 betweenD5Mit133 (32 cM) and D5Mit290 (36 cM) in the F2 intercross population. This locus is named Lfnq1 (lung function QTL 1). Peak linkage to VD occurs at D15Mit255 (LOD=4.4). Sod3 (31 cM) was named as a potential candidate gene for Lfnq1. A distal locus named Lfnq2 (lung function QTL 2) is linked to CL/TLC in the F2 intercross and mapped to 54 cM near D5Mit152 (LOD=4.8). Tgfbr3 is a potential candidate gene for Lfnq2. Three nonconservative polymorphisms were detected between C3H/HeJ and JF1/MsIeg Tgfbr3 sequences.

Significant linkage to all lung function phenotypes mapped to a locus on mouse Chromosome 15 between D15Mit85 (16.4 cM) and D15Mit105 (47.9 cM). This locus is named Lfnq3 (lung function QTL 3). In the backcross population linkage to TLC mappedto 18.2 cM atD15Mit58 (LOD=4.7), TLC/body weight mapped to 17.2 cM at D15Mit268 (LOD=6), linkage to CL mapped to 20.2 cM at D15Mit152 (LOD=4), and linkage to VD mapped to 46 cM between D5Mit146 and D15Mit105 (LOD=4.1). In the F2 population linkage to TLCmapped to20.2 cMat D15Mit152 (LOD=4.9), linkage to CL mapped to 47.9 cM at D15Mit105 (LOD=5), and DCO mapped to 16.4 cM at D15Mit85 (LOD=4.8). Trps1 (30.1 cM) is a potential candidate gene for Lfnq3. Sequence analysis of Trps1 did not detect polymorphisms in C3H/HeJ andJF1/MsIeg. Pdgfb (46.8 cM) is also considered a potential candidate gene. A previously identified bronchial airway hyper-responsiveness QTL named Bhr2 (47.1 cM) maps near the Lfnq3 interval.

Linkage to TLC mapped to three intervals on mouse Chromosome 17(approximately LOD=5) in the backcross population. The first interval spans D17Mit156 (7.1 cM) to D17Mit234 (20.7 cM) and is named Lfnq4 (lung function QTL 4). A previously identified bronchial airway hyper-responsiveness QTL named Bhr3 (14 cM) overlaps withthis interval. The Lfnq4 locus is syntenic to human Chromosome 6q27, a region linked to lung function in humans. Rxrb (18.49 cM) was named as a potential candidate gene for Lfnq4 but sequence polymorphisms between C3H/HeJ and JF1/MsIeg were not detected.Thesecond locus spans D17Mit180 (29.4 cM) to D17Mit20 (34.3 cM) and is named Lfnq5 (lung function QTL 5). The third interval spans D17Mit218 (42 cM) to D17Mit206 (44.5 cM) and is named Lfnq6 (lung function QTL 6). This locus is syntenic to a region on humanChromosome 18implicated in chronic respiratory disease.

On mouse Chromosome 19, linkage to CL mapped to 26.1 cM near D19Mit40 (LOD=5.8). Linkage to CL/TLC mapped to the same place with LOD=6. This locus was identified in the backcross population and isnamed Lfnq7 (lung function QTL 7). Rln1 (21 cM) is a potential candidate gene for Lfnq7. Exon 2 of Rln1 contains 4 nonconservative sequence changes between C3H/HeJ and JF1/MsIeg.

References

• Original: J:131210 Reinhard C, et al., Genomewide linkage analysis identifies novel genetic Loci for lung function in mice. Am J Respir Crit Care Med. 2005 Apr 15;171(8):880-8
• All: 1 reference(s)