Ath6^C57BLKS/J
QTL Variant Detail

Summary

• QTL variant: Ath6^C57BLKS/J
• Name: atherosclerosis 6; C57BLKS/J
• MGI ID: MGI:3044381
• QTL: Ath6 Location: Chr12:15758613-15758756 bp Genetic Position: Chr12, Syntenic

Variant origin

• Strain of Specimen: C57BLKS/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers susceptibility to atherosclerosis compared to C57BL/6J. (J:56090)

Notes

Congenic animals carrying C57BLKS/J-derived DNA at Ath6 (chromosome 12) on a C57BL/6J genetic background display significantly larger lesions on an atherogenic diet compared to background strain C57BL/6J.

Candidate Genes

J:109430

It is believed that the enhanced diabetes susceptibility of C57BLKS/J-Lepr^db animals (compared to C57BL/6J-Lepr^db animals) is conferred by contribution of DBA/2J-derived DNA in the genome. It is estimated that 70% of the C57BLKS/J genome is of C57BL/6J origin, 20% is of DBA/2J origin, and 9% contributed by an unknown donor strain. Extensive SNP analysis using 15,300 SNPs at an average spacing of 167,000 bp on the autosomes and 330,000 bp on the X chromosome mapped blocks of C57BLKS/J genome derived from DBA/2J. In addition, expression analysis of genes in these blocks identified potential diabetes susceptibility candidate genes.

Previously identified QTL Ath6 at 3 cM on mouse Chromosome 12 mapped to one of these DBA/2J-derived blocks from 10.4 Mb to 19.5 Mb. Over 430 genes are found in this interval. Genes exhibiting significant expression differences between C57BL/6J and DBA/2J and correlating with diabetes-related traits were screened. Rrm2 (8 cM; 19.15 Mb; LOD=13.92), Dock4 (16.5 cM; 35.35 Mb; LOD=8.75), and Cfl2 (36.5 cM; 50.275 Mb; LOD=10.33) were identified as Ath6 candidate genes meeting the above criteria.

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

J:56090

Mice from the inbred strain C57BLKS/J (BKS) show increased susceptibility to diabetes and atherosclerosis compared to C57BL/6J mice. The authors carried out a cross between the C57BL/6J-db/db and BKS mice. F1 heterozygous for the db mutation were mated and F2 db/db progeny were tested for fatty acid lesion streaks in the aorta. A marker order and distance was calculated based on the 99 mice in this cross. D12Mit182 - 3 cM - D12Mit169 - 1.5 cM - D12Mit269 - 0.5 cM - D12Mit49 - 4 cM - D12Mit13 - 0.5 cM - D12Mit185 - 4.0 cM - D12Mit221. The authors found that the lesion size was determined by a locus at D12Mit49 with a LOD score of 2.5 and a significant likelihood ratio statistic (LRS) of 11.4. This was confirmed by constructing a congenic strain with BKS alleles in the QTL region on a C57BL/6 genetic background. The lesions of the congenic strains were significantly larger than those of C57BL/6J but not significantly different from that of the BKS strain. The authors have named this locus Ath6. Ath6 was estimated to account for 25% of the variance of lesion size. Three putative candidate genes have been identified in the region: Apob, Adam17 and Synd1.

J:70335

The Ath6 locus was fine mapped using the Jax BSS/BSB mapping panels. Authors determined the order and distance of markers as follows: Centromere - ApoB, D12Mit215 - 0.53 +/- 0.53 cM - D12Mit104, Sdc1 - 0.53 +/- 0.53 cM - D12Mit182, D12Pgn2, D12Pgn3, Mycn, D12Mit209, H1518T7, H1518Sp6, Kcns3, D12Ertd208e, D12Ertd553e - 0.53 +/- 0.53 cM - D12Mit82, D12Mit169 - 21. +/- 1.05 cM - D12Nds11. Ath6 was positioned between D12Pgn4 and Mycn.

J:70335

The Ath6 locus was fine mapped using a (C57BL/6J x C57BLKS/J)F2 intercross population. Authors determined the order and distance of markers as follows: Centromere - M19212Sp6, D12Mit182 - 0.28 +/- 0.21 cM - 83MMHAP83.seq, D12Pgn5, D12Pgn2, D12Pgn3, D12Pgn4 - 0.85 +/- 0.35 cM - Mycn, D12Mit209, D12Pgn6, D12Pgn1, B929Sp6, B340Sp6 - 0.14 +/- 0.12 cM - D12Pgn7 - 0.28 +/- 0.21 cM - D12Mit82, D12Mit169 - 0.28 +/- 0.21 - D12Mit43 - 0.28 +/- 0.21 cM - D12Mit49, D12Mit218, D12Nds11 - 0.14 +/- 0.12 cM - D12Mit269, D12Mit105 - 0.14 +/- 0.12 cM - D12Mit84, D12Mit221, D12Mit2. Ath6 was positioned between D12Pgn4 and Mycn.

J:70335

The Ath6 locus was fine mapped using a (C57BL/6J x C57BLKS/J)F1 x C57BLKS/J backcross population. Authors determined the order and distance of markers as follows: Centromere - M19212Sp6, D12Mit182, 32.MMHAP83FLC5.seq, D12Pgn5,D12Pgn2, D12Pgn3, D12Pgn4 - 1.24 +/- 0.30 cM - Mycn, D12Mit209, D12Pgn6, D12Pgn1, B929Sp6, B340Sp6 - 0.11 +/- 0.11 cM - D12Pgn7 - 0.34 +/- 0.20 cM - D12Mit82 - 0.11 +/- 0.11 cM - D12Mit169. Ath6 was positioned between D12Pgn4 and Mycn.

References

• Original: J:56090 Mu JL, et al., Quantitative trait loci analysis for the differences in susceptibility to atherosclerosis and diabetes between inbred mouse strains C57BL/6J and C57BLKS/J. J Lipid Res. 1999 Jul;40(7):1328-35
• All: 2 reference(s)