Ath32^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ath32^C57BL/6J
• Name: atherosclerosis 32; C57BL/6J
• MGI ID: MGI:3819132
• QTL: Ath32 Location: unknown Genetic Position: Chr13, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased aortic lesion area in animals fed a high fat diet compared to C3H/HeJ. (J:140288)

Notes

Ath32 was identified in Apoe^tm1Unc homozygous animals.

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

J:140288

Linkage analysis was performed on 334 animals from a (B6.129P2-Apoe^tm1Unc/J x C3.129P2(B6)-Apoe^tm1Unc)F2 intercross to identify genetic loci associated with atherosclerosis susceptibility. Animals were fed a CHOW diet until 8 weeks of age and then placed onan atherogenic diet for 16 weeks until sacrifice at 24 weeks of age for phenotype analysis on aortic section histology and plasma lipids. A panel of 1353 SNP markers spaced approximately 1.5 Mb apart was used for genome scan. Several previously identifiedatherosclerosis QTL were detected and five new QTL were identified in this study.

On mouse Chromosome 1, a new atherosclerosis susceptibility locus named Ath30 was identified at 76.4 Mb near rs3689327 (LOD=6.47). This QTL appears to be female-specific(LOD=5.98 in females only). The 95% confidence interval for Ath30 spans 72 Mb to 80 Mb. C57BL/6J-derived alleles at Ath30 confer increased aortic lesion area in female animals. A potential candidate gene for Ath30 is 2310007B03Rik (95 Mb), as identified by eQTL analysis. A previously identified QTL named Ath1 (currently Tnfsf4) was detected at 155.9 Mb near rs3716472 (LOD=7.08). The 95% confidence interval for Ath1 spans 135 Mb to 161 Mb. This locus also appears to be female-specific with C57BL/6J-derived alleles conferring increased aortic lesion area.

On mouse Chromosome 4, QTL Athsq3 was detected at 148.9 Mb near rs3686555 (LOD=4.97). The 95% confidence interval spans 145 Mb to 153 Mb. This locus exhibits sexual antagonism where C57BL/6J-derived allelesconfer increased aortic lesion area in females and C3H/HeJ-derived alleles confer increased aortic lesion area in males.

On mouse Chromosome 5, a suggestive atherosclerosis susceptibility locus was detected at 75.8 Mb nearrs3720626 (LOD=3.99). C57BL/6J-derived alleles confer increase aortic lesion size at this locus.

A novel atherosclerosis QTL was detected at 61.7 Mb on mouse Chromosome 7 near rs3677657 (LOD=6.62). This locus is named Ath31 and appears to be female-specific (LOD=5.32 in females only). C57BL/6J-derived alleles at Ath31 confer increased aortic lesion area in females. The 95% confidence interval spans 50 Mb to 100 Mb. Plekhb1, Blm (87.6 Mb), Iqgap1 (87.8 Mb), Phca (105.3 Mb), and Ndufc2 (104.5 Mb) were identified as potential candidategenes for Ath31 by eQTL analysis.

Previously identified atherosclerosis QTL Ath29 was detected at 84.1 Mb on mouse Chromosome 9 near rs367897 (LOD=8.05). C57BL/6J-derived alleles at Ath29 confer increased aortic lesionareaand the 95% confidence intervalspans 45 Mb to 89 Mb. Expression QTL (eQTL analysis) identified Rbp1 (98.3 Mb), Bco2 (formerly Bcdo2; 50.3 Mb), 23100030G06Rik, Cryab (50.56 Mb), Slc17a5 (78.38 Mb), Anp32a (62.1 Mb), and Cadm1 (formerly Igsf4a; 47.3 Mb)aspotential candidate genes for Ath29.

A female-specific QTL Ath15 was detected at 104.1 Mb on mouse Chromosome 11 near rs3722158 (LOD=7.76). The 95% confidence interval for Ath15 spans 64 Mb to 113 Mb. C57BL/6J-derived alleles at Ath15 confer increased aorticlesion size in female animals.Potential candidate genes for Ath15 as determined by overlapping eQTL analysis include 5530600A18Rik (94.1 Mb) and Syngr2 (117.67 Mb).

A novel atherosclerosis locus named Ath32 mapped to 89.6 Mb on mouse Chromosome 13 nearrs3660479 (LOD=6.93). The 95% confidence interval for Ath32 spans 86 Mb to 110 Mb with C57BL/6J-derived alleles conferring increased aortic lesion area. Serinc5 (formerly A130038L21Rik; 93.3 Mb) and Hexb (97.9 Mb) are potential candidate genes for Ath32 asdetermined by overlappingeQTLanalysis.

Ath33 mapped to 71.4 Mb on mouse Chromosome 15 near rs3696862 (LOD=6.2). C3H/HeJ-derived alleles at Ath33 confer increased aortic lesion area. The 95% confidence interval for Ath33 spans 67 Mb to 78 Mb. ExpressionQTL (eQTL) analysis identifiedCsf2rb2 (78.1 Mb) and Slc39a4 (76.4 Mb) as potential candidate genes for Ath33.

A previously identified atherosclerosis QTL named Ath26 was detected at 26.1 Mb on mouse Chromosome 17 near rs4231406 (LOD=4.28). C57BL/6J-derived alleles at Ath26 conferincreased aortic lesion area. The 95% confidence interval for Ath26 spans 22 cM to 28 cM.

References

• Original: J:140288 Wang SS, et al., Identification of pathways for atherosclerosis in mice: integration of quantitative trait locus analysis and global gene expression data. Circ Res. 2007 Aug 3;101(3):e11-30
• All: 1 reference(s)