Binenbaum, IlonaAtamni, Hanifa Abu-ToamihFotakis, GeorgiosKontogianni, GeorgiaKoutsandreas, TheodorosPilalis, EleftheriosMott, RichardHimmelbauer, HeinzIraqi, Fuad A.Chatziioannou, Aristotelis A.2020-12-162020-12-162020Binenbaum, I Abu-Toamih Atamni H, Fotakis G, Kontogianni G,Koutsandreas T, Pilalis E et al. Container-aided integrative QTL and RNA-seq analysis of Collaborative Cross mice supports distinct sex-oriented molecular modes of response in obesity. BMC Genomics. 2020 Nov 3; 21(1): 761. DOI: 10.1186/s12864-020-07173-x1471-2164http://hdl.handle.net/10230/46057Background: The Collaborative Cross (CC) mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population. Results: We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrated these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms. Conclusion: Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity are different in female and male mice. The clear distinction we observed in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.application/pdfeng© Ilona Binenbaum et al 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were madeObesitatSeqüència de nucleòtidsDiferències entre sexesContainer-aided integrative QTL and RNA-seq analysis of Collaborative Cross mice supports distinct sex-oriented molecular modes of response in obesityinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s12864-020-07173-xinfo:eu-repo/semantics/openAccess