Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line

Autor: Detlef Zillikens, Christian D. Sadik, Anna Lara Ernst, Paul Schilf, Moritz Steinhaus, Hiroshi Nishi, Marc Ehlers, Stanislav Khil’chenko, Christian Sina, Artem Vorobyev, Hiroshi Koga, Wolf-Henning Boehncke, John F. Baines, Steffen Möller, Ralf Ludwig, Rudolf A. Manz, Katja Bieber, Heiko Körber-Ahrens, Yannic C. Bartsch, Yask Gupta, Sven Künzel, Joanna Jascholt, Phillip Kouki, Tanya N. Mayadas, Meriem Belheouane, Tanya Sezin, Saleh M. Ibrahim, Hassanin Al-Aasam, Sandra Diehl, Foteini Beltsiou
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Candidate gene
General Physics and Astronomy
Autoimmunity
ddc:616.07
Spleen/metabolism
Mice
0302 clinical medicine
Genetics research
Gene–environment interaction
lcsh:Science
2. Zero hunger
Genetics
ddc:616
Multidisciplinary
Microbiota
Antibodies
Antinuclear/genetics
outbred mouse line
Biodiversity
Transcriptome/genetics
Physical Chromosome Mapping
Lupus Nephritis
030220 oncology & carcinogenesis
Antibodies
Antinuclear
Female
Bacteria/growth & development
medicine.medical_specialty
Quantitative trait loci
Fungi/growth & development
Science
Single-nucleotide polymorphism
Biology
Quantitative trait locus
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Quantitative Trait
Heritable
Molecular genetics
Genetic predisposition
medicine
Animals
Outbred Strains
Animals
Genetic Predisposition to Disease
Crosses
Genetic
Genetic Association Studies
Genetic association
Genetic association study
Bacteria
Whole Genome Sequencing
Fungi
General Chemistry
Phenotypic trait
Diet
030104 developmental biology
Genes
lcsh:Q
Transcriptome
Quantitative Trait Loci/genetics
Lupus Nephritis/genetics/immunology
Spleen
Zdroj: Nature Communications
Nature Communications, Vol. 10, No 1 (2019) P. 4097
Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019)
ISSN: 2041-1723
Popis: Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive. To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL). By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes. To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice. Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation. Collectively, our study underlines the importance of including environmental factors in genetic association studies.
Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.
Databáze: OpenAIRE
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