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 10 (C57BL/6J-Chr 10A/J/NaJ x C57BL/6J) the following significant QTL were identified:
Obrq5 (obesity resistance QTL 5) mapped to Chr 10 at 65 cM in a 1.5 LOD support interval between 57-90 cM with a LOD=5.82, p=0.006 for trait MW.
Obrq8 (obesity resistance QTL 8) mapped to 95 cM in a 1.5 LOD support interval between 79-103 cM with a LOD=6.80, p=0.001 for trait EWG.
Curator Note: Table 3 equated the QTL Obrq8 above with QTL Obrq5. However different traits are being measured so we have assigned novel nomenclature to each QTL. Note also that in the same Table 3, a suggestive QTL on Chr 17 was also named Obrq8, however suggestive QTL are not assigned offical nomenclature.
The following suggestive QTL were also identified on Chr 10:
at 62 cM, spanning 25-103 cM, LOD=3.21, p=0.55, affecting trait FW;
at 65 cM, spanning 56-80 cM, LOD=3.16, p=0.58, affecting trait IW; and
at 90 cM, spanning 68-103 cM, LOD=3.50, p=0.36, infuencing trait WG.
[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 10 for FW at 101 cM, p=0.347, 1.5 LOD support interval between 83 and 101 cM; and for BMI at 101 cM, p=0.184, 1.5 LOD support interval between 80 and 101 cM. [Sup Table 7].
Analysis Tools