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