Otto, GW;
Kaisaki, PJ;
Brial, F;
Le Lay, A;
Cazier, J-B;
Mott, R;
Gauguier, D;
(2019)
Conserved properties of genetic architecture of renal and fat transcriptomes in rat models of insulin resistance.
Disease Models & Mechanisms
, 12
(7)
10.1242/dmm.038539.
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Abstract
To define renal molecular mechanisms that are affected by permanent hyperglycemia and may promote phenotypes relevant to diabetes nephropathy, we carried out linkage analysis of genome-wide gene transcription in kidney of F2 offspring from the Goto-Kakizaki (GK) rat model of type 2 diabetes and normoglycemic Brown Norway (BN) rats. We mapped 2526 statistically significant expression quantitative trait loci (eQTLs) in the cross. Over 40% of eQTLs mapped in the close vicinity of the linked transcripts, underlying possible cisregulatory mechanisms of gene expression. We identified eQTL hotspots on chromosomes 5 and 9 regulating the expression of 80-165 genes, sex or cross direction effects, and enriched metabolic and immunological processes by segregating GK alleles. Comparative analysis with adipose tissue eQTLs in the same cross showed that 496 eQTLs, as well as top enriched biological pathways, are conserved in the two tissues. Extensive similarities in eQTLs mapped in the GK and in the spontaneously hypertensive rat (SHR) suggest a common etiology of disease phenotypes common to the two strains, including insulin resistance which is a prominent pathophysiological feature in both GK and SHR. Our data shed light on shared and tissue specific molecular mechanisms that may underlie etiological aspects of insulin resistance in the contexts of spontaneously occurring hyperglycemia and hypertension.
| Type: | Article |
|---|---|
| Title: | Conserved properties of genetic architecture of renal and fat transcriptomes in rat models of insulin resistance |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dmm.038539 |
| Publisher version: | https://doi.org/10.1242/dmm.038539 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | eQTL, Goto-Kakizaki Rat, Diabetes Mellitus, Genetic Crosses, Insulin Resistance, Quantitative Trait Locus, SHR, Single Nucleotide Polymorphism, Spontaneously Hypertensive rat, Systems Genetics, Transcriptome. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10077083 |
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