Please use this identifier to cite or link to this item: https://doi.org/10.1242/dmm.026104
Title: From integrative genomics to systems genetics in the rat to link genotypes to phenotypes
Authors: Moreno-Moral, A 
Petretto, E 
Keywords: transcriptome
cardiovascular disease
copy number variation
epigenetics
gene expression
gene identification
gene mapping
gene regulatory network
genetic regulation
genetics
genome analysis
genomics
genotype phenotype correlation
inflammatory disease
integrative genomics
metabolic disorder
metabolome
molecular biology
nonhuman
priority journal
quantitative trait locus
quantitative trait locus mapping
rat
Review
signal transduction
systems genetics
animal
diseases
genetic association study
genetics
genotype
phenotype
systems biology
Animals
Disease
Genetic Association Studies
Genomics
Genotype
Phenotype
Rats
Systems Biology
Issue Date: 2016
Citation: Moreno-Moral, A, Petretto, E (2016). From integrative genomics to systems genetics in the rat to link genotypes to phenotypes. DMM Disease Models and Mechanisms 9 (10) : 1097-1110. ScholarBank@NUS Repository. https://doi.org/10.1242/dmm.026104
Abstract: Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emergedas 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. © 2016. Published by The Company of Biologists Ltd.
Source Title: DMM Disease Models and Mechanisms
URI: https://scholarbank.nus.edu.sg/handle/10635/173817
ISSN: 17548403
DOI: 10.1242/dmm.026104
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