Experiment
The C57BL/6J-ChrA/J/NaJ (B6.A) panel of chromosome substutution strains (CSSs) is a unique model for studying resistence to diet induced obesity. C57BL/6J male mice are significantly more susceptible than A/J males to diet induced obesity. In the present study 20 CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTL) on individual chromosomes.
CSS females were crossed with C57BL/B6 (B6) males), F1 offspring were then intercrossed to generate F2 male progeny, 75-93 per CSS cross. QTL analysis on the intercosses between each CSS strain (except CSS-Y and CSS-Mito) and the B6 host strain revealed significant QTL on Chromosomes 1, 6, 10, 11, and 13. The analysis was performed testing for QTL that affected:
IW, weight in grams at app 35 days of age;
MW, weight in grams at app 90 days of age;
FW, weight in grams at app 135 days of age;
BMI, FW in grams / final nasonanal length in cms;
EWG, mean weight gain per day in grams/day for app first 55 days;
FWG, mean weight gain per day in grams per day for second app 45 days;
WG, mean weight gain per day in grams/per day.
On Chromosome 6 (C57BL/6J-Chr 6A/J/NaJ x C57BL/6J) the following significant QTL was identified:
Obrq20(obesity resistance QTL 20) mapped to Chr 6 at 56 cM in a 1.5 LOD support interval between 51-62 cM with a LOD=5.03, p=0.023 for trait BMI.
Curator Note: Table 3 equated this QTL with existing QTL Obrq1. However because Obrq1 was originally identified in J:142667 examining the obesity trait, which differed in measurement from the BMI trait examined here we regard this QTL as novel and have named it Obrq20.
The following suggestive QTL were also identified on Chr 6:
at 28 cM and at 57 cM, spanning 20-33 and 37-76 cM respectivly, a single LOD=3.78 and p=0.025 value are reported affecting trait FW;
at 56 cM, spanning 39-64 cM, LOD=3.29, p=0.53 affecting trait MW;
at 43 cM, spanning 36-73 cM, LOD=4.25, p=0.10 affecting trait WG;
at 28 cM and at 72 cM, spanning 18-33 and 51-83 cM respectively, a single LOD=4.33, p=0.09 value are reported affecting trait FWG.
[Table 2 and Sup Table 5].
QTL analysis was performed using 94 (C57BL/6J x A/J) intercross progeny to test whether QTL detected in the CSS were comparable to those detected using a traditional intercross between the parental strains.
No significant QTL were detected in the parental strain intercross. However, suggestive QTL were identified on Chr 6 for FW at 24.4 cM, p=0.407, 1.5 LOD support interval bwtween 17 and 32 cM; and for WG at 60.6 cM, p=0.583, 1.5 LOD support interval between 0 and 88 cM. [Sup Table 7].
Analysis Tools