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From integrative genomics to systems genetics in the rat to link genotypes to phenotypes.

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Title: From integrative genomics to systems genetics in the rat to link genotypes to phenotypes.
Authors: Moreno-Moral, A
Petretto, E
Item Type: Journal Article
Abstract: Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emerged as powerful strategies to decipher the key genetic drivers of molecular pathways that underlie disease. Broadly speaking, integrative genomics aims to link cellular-level traits (such as mRNA expression) to the genome to identify their genetic determinants. With the characterization of several cellular-level traits within the same system, the integrative genomics approach evolved into a more comprehensive study design, called systems genetics, which aims to unravel the complex biological networks and pathways involved in disease, and in turn map their genetic control points. The first fully integrated systems genetics study was carried out in rats, and the results, which revealed conserved trans-acting genetic regulation of a pro-inflammatory network relevant to type 1 diabetes, were translated to humans. Many studies using different organisms subsequently stemmed from this example. The aim of this Review is to describe the most recent advances in the fields of integrative genomics and systems genetics applied in the rat, with a focus on studies of complex diseases ranging from inflammatory to cardiometabolic disorders. We aim to provide the genetics community with a comprehensive insight into how the systems genetics approach came to life, starting from the first integrative genomics strategies [such as expression quantitative trait loci (eQTLs) mapping] and concluding with the most sophisticated gene network-based analyses in multiple systems and disease states. Although not limited to studies that have been directly translated to humans, we will focus particularly on the successful investigations in the rat that have led to primary discoveries of genes and pathways relevant to human disease.
Issue Date: 5-Oct-2016
Date of Acceptance: 1-Oct-2016
URI: http://hdl.handle.net/10044/1/42044
DOI: http://dx.doi.org/10.1242/dmm.026104
ISSN: 1754-8411
Publisher: Company of Biologists
Start Page: 1097
End Page: 1110
Journal / Book Title: Disease Models & Mechanisms
Volume: 9
Issue: 10
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Gene network
Integrative genomics
Rat
Systems genetics
eQTL
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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