Experiment
The authors evaluated the responses to different levels of fat in the diet using both chow diet (CD, 13-18% fat) and a high-fat diet (HFD, 45-60% fat).
The authors studied cohorts of BXD strains, both inbred parents C57BL/6J and DBA/2J, as well as (C57BL/6J x DBA/2J) and (DBA/2J x C57BL/6J) reciprocal F1 hybrids.
The parents of the BXDs and F1 hybrids express limited differences in terms of weight and body fat gain on CD. In contrast, the strain differences on HFD are substantial for percent body fat, with DBA/2J accumulating 12.5% more fat than C57BL/6J (P < 0.0001). The F1 hybrids born to DBA/2J dams ((DBA/2J x C57BL/6J)F1) have 10.6% more body fat (P < 0.001) than those born to C57BL/6J dams.
The comparative impact of genetic and dietary factors was analyzed by profiling a range of phenotypes, most prominently cecum bacterial composition.
QTL mapping was based on the regression of the 3,785 polymorphic DNA markers on the targeted phenotypes using QTL Reaper. All coordinates are relative to GRCm38.
Host genetics modulates variation in cecum bacterial composition at the genus level in CD, with significant QTL for Oscillibacter and Bifidobacterium:
Cbcq1 (cecum bacterial composition QTL 1) maps to Chr 3: 18.7 - 19.2 Mb with a peak LRS score of 21.4 and explains 5.6% of the phenotypic variance. The abundance of Oscillibacter in BXD cecum was increased by the DBA/2J allele.
Cbcq2 (cecum bacterial composition QTL 2) maps to Chr 6: 89.21 - 89.37 Mb with a peak LRS score of 19.4 and explains 11.3% of the phenotypic variance. The abundance of Bifidobacterium was increased by the C57BL/6J allele.
Analysis Tools