Faculty Collaboration Database

Analysis of disease-associated objects at the Rat Genome Database. Database (Oxford) 2013;2013:bat046

Date

06/26/2013

Pubmed ID

23794737

Pubmed Central ID

PMC3689439

DOI

10.1093/database/bat046

Scopus ID

2-s2.0-84885941569 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

The Rat Genome Database (RGD) is the premier resource for genetic, genomic and phenotype data for the laboratory rat, Rattus norvegicus. In addition to organizing biological data from rats, the RGD team focuses on manual curation of gene-disease associations for rat, human and mouse. In this work, we have analyzed disease-associated strains, quantitative trait loci (QTL) and genes from rats. These disease objects form the basis for seven disease portals. Among disease portals, the cardiovascular disease and obesity/metabolic syndrome portals have the highest number of rat strains and QTL. These two portals share 398 rat QTL, and these shared QTL are highly concentrated on rat chromosomes 1 and 2. For disease-associated genes, we performed gene ontology (GO) enrichment analysis across portals using RatMine enrichment widgets. Fifteen GO terms, five from each GO aspect, were selected to profile enrichment patterns of each portal. Of the selected biological process (BP) terms, 'regulation of programmed cell death' was the top enriched term across all disease portals except in the obesity/metabolic syndrome portal where 'lipid metabolic process' was the most enriched term. 'Cytosol' and 'nucleus' were common cellular component (CC) annotations for disease genes, but only the cancer portal genes were highly enriched with 'nucleus' annotations. Similar enrichment patterns were observed in a parallel analysis using the DAVID functional annotation tool. The relationship between the preselected 15 GO terms and disease terms was examined reciprocally by retrieving rat genes annotated with these preselected terms. The individual GO term-annotated gene list showed enrichment in physiologically related diseases. For example, the 'regulation of blood pressure' genes were enriched with cardiovascular disease annotations, and the 'lipid metabolic process' genes with obesity annotations. Furthermore, we were able to enhance enrichment of neurological diseases by combining 'G-protein coupled receptor binding' annotated genes with 'protein kinase binding' annotated genes. Database URL: http://rgd.mcw.edu

Author List

Wang SJ, Laulederkind SJ, Hayman GT, Smith JR, Petri V, Lowry TF, Nigam R, Dwinell MR, Worthey EA, Munzenmaier DH, Shimoyama M, Jacob HJ

Authors

Melinda R. Dwinell PhD Associate Dean, Professor in the Physiology department at Medical College of Wisconsin
Stanley J. Laulederkind Research Scientist II in the Physiology department at Medical College of Wisconsin
Shur-Jen Wang Research Scientist II in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cardiovascular Diseases
Chromosomes, Mammalian
Databases, Genetic
Disease
Genetic Association Studies
Genetic Predisposition to Disease
Genome
Humans
Mice
Molecular Sequence Annotation
Nervous System Diseases
Obesity
Quantitative Trait Loci
Rats
Software