| First Author | Garrett NE 3rd | Year | 2017 |
| Journal | Mamm Genome | Volume | 28 |
| Issue | 3-4 | Pages | 90-99 |
| PubMed ID | 28116503 | Mgi Jnum | J:250327 |
| Mgi Id | MGI:5921819 | Doi | 10.1007/s00335-016-9677-0 |
| Citation | Garrett NE 3rd, et al. (2017) Genetic analysis of a mouse cross implicates an anti-inflammatory gene in control of atherosclerosis susceptibility. Mamm Genome 28(3-4):90-99 |
| abstractText | Nearly all genetic crosses generated from Apoe-/- or Lldlr-/- mice for genetic analysis of atherosclerosis have used C57BL/6 J (B6) mice as one parental strain, thus limiting their mapping power and coverage of allelic diversity. SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice differ significantly in atherosclerosis susceptibility. 224 male F2 mice were generated from the two Apoe -/- strains to perform quantitative trait locus (QTL) analysis of atherosclerosis. F2 mice were fed 5 weeks of Western diet and analyzed for atherosclerotic lesions in the aortic root. Genome-wide scans with 144 informative SNP markers identified a significant locus near 20.2 Mb on chromosome 10 (LOD score: 6.03), named Ath48, and a suggestive locus near 49.5 Mb on chromosome 9 (LOD: 2.29; Ath29) affecting atherosclerotic lesion sizes. Using bioinformatics tools, we prioritized 12 candidate genes for Ath48. Of them, Tnfaip3, an anti-inflammatory gene, is located precisely underneath the linkage peak and contains two non-synonymous SNPs leading to conservative amino acid substitutions. Thus, this study demonstrates the power of forward genetics involving the use of a different susceptible strain and bioinformatics tools in finding atherosclerosis susceptibility genes. |
