Rat Genome Database: a unique resource for rat, human, and mouse quantitative trait locus data

Abstract

The rat has been widely used as a disease model in a laboratory setting, resulting in an abundance of genetic and phenotype data from a wide variety of studies. These data can be found at the Rat Genome Database (RGD, http://rgd.mcw.edu/), which provides a platform for researchers interested in linking genomic variations to phenotypes. Quantitative trait loci (QTLs) form one of the earliest and core datasets, allowing researchers to identify loci harboring genes associated with disease. These QTLs are not only important for those using the rat to identify genes and regions associated with disease, but also for cross-organism analyses of syntenic regions on the mouse and the human genomes to identify potential regions for study in these organisms. Currently, RGD has data on >1,900 rat QTLs that include details about the methods and animals used to determine the respective QTL along with the genomic positions and markers that define the region. RGD also curates human QTLs (>1,900) and houses>4,000 mouse QTLs (imported from Mouse Genome Informatics). Multiple ontologies are used to standardize traits, phenotypes, diseases, and experimental methods to facilitate queries, analyses, and cross-organism comparisons. QTLs are visualized in tools such as GBrowse and GViewer, with additional tools for analysis of gene sets within QTL regions. The QTL data at RGD provide valuable information for the study of mapped phenotypes and identification of candidate genes for disease associations.

Keywords: QTL; Rat Genome Database; mapping.

Fig. 1.

Quantitative trait locus (QTL) search page. A: the keyword search box is found in the upper right corner of most pages on the Rat Genome Database (RGD) website. B: the keyword search box on the QTL search page specifically searches QTL-associated data fields. The search can also be limited by chromosomal location, genomic assembly, and species.

Fig. 2.

General keyword search result page listing all RGD objects that have the term “blood pressure” in them.

Fig. 3.

Classic QTL search entry page. The QTL search on this page can be limited by a variety of parameters including chromosome, logarithm of odds (LOD) score, P value, trait, and others.

Fig. 4.

Ontology general search page. A: any of the ontologies/vocabularies used to annotate QTLs can be searched on this page. B: the search for “arterial blood pressure” returns a list of ontologies/vocabularies that have terms containing the searched word or phrase. In this case the Clinical Measurement Ontology (CMO) has been selected, and 5 terms have been returned in the right frame (C). When the term “mean arterial blood pressure” is selected, the Ontology Report page is returned with all objects annotated to that term displayed in the Genome Viewer (GViewer) (chromosome display) and listed below in a table. All QTL symbols in the list are hyperlinked to the respective QTL report pages.

Fig. 5.

A: typical RGD QTL report page showing the general information section along with a strain report linked from the QTL page and a PhenoMiner details table linked from the strain page. B: annotation section of the QTL report page displaying candidate gene along with a gene page linked from the QTL page and an allele page linked to the gene page. In addition, the “Experimental Data Annotations” and “RGD Disease Portals” subsections have been expanded to show details. C: region section; D: additional Information section.

Fig. 6.

GBrowser at RGD showing the QTLs that lie in the same region as the rat gene Nppa, with a balloon pop-up that gives detailed information related to QTL Bp155 when the cursor hovers over the Bp155 track.

Fig. 7.

GViewer at RGD showing the annotated genes, QTLs, and congenic strains that are associated with the cardiovascular portal.