PMC

Allele effect plot of the main effect QTL for triglycerides. Triglyceride levels are indicated as mean ±SD in mg/ml at each QTL, using the closest marker for each genotype (MM, homozygous MRL; MS, heterozygous; SS, SM homozygous).

Using the bioinformatic tools to narrow the significant QTL for triglycerides on Chr 7 (A), Chr 15 (B), and Chr 17 (C). Each panel shows the relevant bioinformatic tools used to reduce the confidence interval of the QTL (upper bar) with haplotype analysis (middle bar). Each gene within the locus is examined for additional molecular evidence (lower bar), whether it shows either an amino acid change that is potentially functional using SIFT (on the top of the lower bar) or differential expression in males or females between MRL and SM, whether it is cis-regulated, and whether it significantly correlates with the phenotype (on the bottom of the lower bar) in the F2 mice. For the haplotype analysis, we looked for regions that were different between MRL and SM. The number of genes is indicated for each step. The best candidate genes are indicated for each QTL with an asterisk at their respective locations and are also presented in with their evidence.

Genome-wide scan for triglycerides in 282 F2 mice. Analysis was performed with sex as an (A) additive covariate and (B) interactive covariate. The difference between both models (B) with a delta LOD > 2 indicates a QTL by sex interaction (dotted line). Analysis was also performed in males (C) and females (D) separately. For each model, data were permuted 1,000 times to determine the genome-wide level of significance. The threshold of significance for Chr X was determined with 17,940, 16,784, and 19,085 permutations in the combined sex, male-only, and female-only analyses, respectively. In the combined sex analysis (A and B), the suggestive and significant thresholds for the autosomes were 2.2 and 3.7, respectively, in the additive model, and 3.2 and 5.0, respectively, in the interactive model. For the X chromosome, the suggestive and significant thresholds were 2.1 and 3.6, respectively, for the additive and the interactive models. In males and females alone (C and D), the suggestive and significant thresholds were 2.2 and 3.6, respectively. For the X chromosome, the suggestive and significant thresholds were 1.4 and 2.7, respectively, in males, and 2.5 and 2.8, respectively, in females. The dashed line represents the threshold of P = 0.05, and the dash-dotted line represents the threshold for suggestive QTL (P = 0.63).