Shali2^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Shali2^C57BL/6J
• Name: survival time to hyperoxic acute lung injury 2; C57BL/6J
• MGI ID: MGI:3767301
• QTL: Shali2 Location: Chr4:124055093-141572792 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to hyperoxic acute lung injury compared to 129X1/SvJ. (J:127224)
• Inheritance: Dominant

Notes

Shali2 interacts with Shali1 on chromosome 1. Animals homozygous for C57BL/6J-derived alleles at Shali2 and homozygous for 129X1/SvJ-derived alleles at Shali1 display the highest resistance to hyperoxic acute lung injury.

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

J:127224

Linkage analysis was performed on 840 reciprocally intercrossed F2 animals derived from 129X1/SvJ and C57BL/6J in order to identify genetic loci for sensitivity to hyperoxia-induced acute lung injury (HALI). Parental strain 129X1/SvJ displays resistance to HALI with longer survival times at 95% oxygen exposure compared to the sensitive C57BL/6J strain. A total of 97 polymorphic markers were genotyped in the F2 population.

Significant linkage to HALI survival time mapped to 62.84 Mb (34.8 cM) on mouse Chromosome 1 near D1Mit303 (LOD=9.4) and is named Shali1 (survival time to hyperoxic acute lung injury 1). 129X1/SvJ-derived alleles at Shali1 confer increased survival time with a dominant mode of inheritance and a more significant effect in females compared to males. This locus appears to be affected by parent-of-origin, which is suggestive of imprinting. The 1.5-LOD support interval spans 49 Mb - 73 Mb. Candidate genes in this interval include Casp8 (30.1 cM), Cflar (30.1 cM), and Il8rb (40 cM). Shali1 appears to interact with other HALI survival time loci on chromosome 4 (Shali2), chromosome 9 (Shali4), and chromosome 15 (Shali3). F2 animals homozygous for 129X1/SvJ-derived alleles at Shali1 and homozygous for C57BL/6J-derived alleles at Shali2 displayed the highest resistance to HALI. A distal male-specific locus mapped to 174 Mb with LOD=3.5 and is named Shali5 (survival time to hyperoxic acute lung injury 5). The 1.5 LOD support interval is flanked by D1Mit34 (81.6 cM) and D1Mit361 (101.5 cM). C57BL/6J-derived alleles at Shali5 confer resistance to HALI in males. Prdx6 at 83.6 cM is a potential candidate gene for Shali5.

Shali2 (survival time to hyperoxic acute lung injury 2) mapped to 120 Mb (57.4 cM) on mouse Chromosome 4 near D4Mit308 (LOD=6.4).C57BL/6J-derived alleles at Shali2 confer resistance to HALI with a dominant mode of inheritance. Shali2 has a more significant effect in males compared to females and may be influenced by imprinting. The 1.5-LOD support interval spans 58 Mb - 145 Mb. Potential candidate genes found in this interval include Tlr4 (33 cM), Txn1 (24.6 cM), Casp9, and Pafah2. The presence of 2 significant peaks in the Shali2 interval suggests this locus is composed of multiple linked QTLs.

Shali3 (survival time to hyperoxicacute lung injury 3) mapped to mouse Chromosome 15 between D15Mit175 (9.9 cM) and D15Mit5 (22.2 cM) with LOD=4.8. The 1.5 LOD support interval spans 0 Mb - 70 Mb. It is unclear which allele confers greater resistance to HALI. Potential candidate genes for Shali3 include Angpt1 (14.3 cM) and Oxr1.

Shali4 (survival time to hyperoxic acute lung injury 4) mapped to 116.1 Mb (66 cM) on mouse Chromosome 9 near D9Mit137 (LOD=3.7). The 1.5 LOD support interval spans 94 Mb to the terminus. C57BL/6J-derived alleles confer resistance to HALI with a dominant mode of inheritance. Potential candidate genes for Shali4 include Gpx1 (57 cM) and Mst1r (60 cM).

A locus on mouse Chromosome 18 at 41 cM (D18Mit184) shows significant interaction with Shali1 on chromosome 1(LOD=5.8). This locus is not significant on its own and may be a modifier for Shali1. 129X1/SvJ-derived alleles at D18Mit184 appear to support the HALI resistant effect of 129X1/SvJ alleles at Shali1.

J:153480

The complex disorder of morbidity and mortality associated with acute lung injury (ALI) and acute respiratory distress syndrome were analyzed in mice to find QTL that effect survival rates. Acute lung injury survival time was identified as C57BL/6J being sensitive and 129X1/SvJ as resistant. QTL analysis was done in 935 backcross mice from 8 various backcross designs using C57BL/6J and 129X1/SvJ mice.

Shali1 mapped between D1Mit478 and D1Mit251 with a peak LOD support of 6.0 with D1Mit303. This peak support includes a region of genomic DNA from 54 - 68 Mbp.

Shali2 mapped between D4Mit308 to D4Mit65 with a peak LOD support of 5.5 ( marker not shown). This peak support include a region of genomic DNA from 104 Mbp to the end.

These loci were previously mapped in J:127224

References

• Original: J:127224 Prows DR, et al., Genetic analysis of hyperoxic acute lung injury survival in reciprocal intercross mice. Physiol Genomics. 2007 Aug 20;30(3):271-81
• All: 2 reference(s)