Mapping the epistatic network underlying murine reproductive fatpad variation.
Genome-wide mapping analyses are now commonplace in many species and several networks of interacting loci have been reported. However, relatively few details regarding epistatic interactions and their contribution to complex trait variation in multicellular organisms are available and the identification of positional candidate loci for epistatic QTL (epiQTL) is hampered, especially in mammals, by the limited genetic resolution inherent in most study designs. Here we further investigate the genetic architecture of reproductive fatpad weight in mice using the F(10) generation of the LG,SM advanced intercross (AI) line. We apply multiple mapping techniques including a single-locus model, locus-specific composite interval mapping (CIM), and tests for multiple QTL per chromosome to the 12 chromosomes known to harbor single-locus QTL (slQTL) affecting obesity in this cross. We also perform a genome-wide scan for pairwise epistasis. Using this combination of approaches we detect 199 peaks spread over all 19 autosomes, which potentially contribute to trait variation including all eight original F(2) loci (Adip1-8), novel slQTL peaks on chromosomes 7 and 9, and several novel epistatic loci. Extensive epistasis is confirmed involving both slQTL confidence intervals (C.I.) as well as regions that show no significant additive or dominance effects. These results provide important new insights into mapping complex genetic architectures and the role of epistasis in complex trait variation.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. jarvisj@mail.med.upenn.edu
Joseph P
JP
Jarvis
James M
JM
Cheverud
D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004843:Epistasis, Genetic; D055106:Genome-Wide Association Study; D051379:Mice; D009765:Obesity / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012098:Reproduction / Q000235:genetics*