期刊
BMC GENOMICS
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12864-020-07173-x
关键词
Collaborative Cross; Obesity; Sex-differences; High-fat diet; QTL; RNAseq
资金
- Operational ProgramCompetitiveness, Entrepreneurship and Innovation 2014-2020 (European Regional Development Fund)
- BioS: Digital Skills on Computational Biology, ERASMUS+ [EACEA/04/2017]
- Hendrech and Eiran Gotwert Fund
- Wellcome Trust [085906/Z/08/Z, 075491/Z/04, 090532/Z/09/Z]
- Tel-Aviv University (TAU)
- Israeli Science foundation (ISF) [429/09, 1085/18]
- Binational Science Foundation (BSF) [2015077]
- German Israeli Science Foundation (GIF) [I-63-410.20-2017]
- European Sequencing and Genotyping Infrastructure (ESGI) consortium grant
- State Scholarship Foundation in Greece (IKY) (Operational Program Human Resources Development -Education and Lifelong Learning Partnership Agreement (PA) 2014-2020)
- Dir for Tech, Innovation, & Partnerships
- Translational Impacts [2015077] Funding Source: National Science Foundation
- Wellcome Trust [085906/Z/08/Z] Funding Source: Wellcome Trust
Background 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.
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