QTL Help

Definition of a QTL

A Quantitative Trait Locus(QTL) is a physical chromosomal location which contains alleles that differentially affect the expression of a continuously distributed phenotypic trait. Usually it is an area(locus) delineated by strain specific markers. If genetic variation in the locus is statistically associated with measured variation in the trait, a QTL results.

A disease-specific QTL in a rat model is obtained by genetic crossing and analysis and is expected to contain one to many genetic elements that would be contributing to the phenotype in the rat. An affected strain (showing the phenotype) is crossed with an unaffected strain (lacking the phenotype), the progeny are genotyped and phenotyped and through statistical techniques, a correlation is made between a particular genotype and the phenotype being measured.

For a comprehensive review of QTL mapping techniques in the rat see "Genetic Analysis of Inherited Hypertension in the Rat" by John Rapp, Physiological Reviews, 90:135-172,2000

 

Searching for QTLs

RGD provides several methods for locating information on QTLs. Users can either perform quick or specific queries to obtain information.

1. RGD Search:

This will search QTL symbols, names, aliases, trait name, subtrait name, trait description/method, and annotations. (See General RGD Search help for more information).

 

Quick Guide

  1. Go to http://rgd.mcw.edu
  2. Enter symbol or keyword in search box in the upper right
  3. Click  

Classic Search

Additional search parameters allow you to refine your searches. 

  1. QTL Symbol/Alias/Name  Enter a QTL symbol, alias or keyword. This tool will search the QTL symbol, name and alias (synonym) fields in the database. The asterisk '*' is an accepted wildcard. In addition, various other options are available to refine the search (See below). 
  2. Annotations  Search for QTLs based on your keyword matching curated annotations. These include free text and controlled vocabulary (Disease and Phenotype ontologies). When searching ontologies the terms' synonyms and descendant terms will also be searched. 
  3. Trait  Restrict the returned QTLs to those detected for a particular phenotypic trait. The traits currently listed are those reported by the researcher in the publication. A controlled vocabulary to describe these more uniformly is under development. 
  4. Strains  Restrict the returned QTLs to those detected using a particular strain.
  5. Chromosome  Restrict the returned QTLs to ones mapped to a particular chromosome. The limit may also include the start and stop coordinates on the genome assembly version listed next to the input boxes.
  6. Limit to QTLs with LOD score greater than  Restrict the returned QTLs to those with a reported LOD score of greater than the value provided.
  7. Limit to QTLs with P-value greater than 0 and less than 1  Restrict the returned QTLs to those with a reported P-value of less than the value provided, but between 0 and 1.

Results ordered by

  • Symbol - sorts returned results alphabetically by QTL symbol
  • Name - sorts returned results alphabetically by QTL name
  • Chromosome - sorts returned results by chromosome (Text ordering not number)
  • LOD -sorts returned results by ascending LOD score
  • P-value -sorts returned results by ascending P-value
  • Trait - sorts returned results alphabetically by Trait name

Results per page

Indicates the number of hits that are returned on the first results page.

The result page also lists the parameters that were used to query the database.


 
  1. Enter a QTL symbol, alias or keyword.  
  2. Annotations  Search for QTLs based on your keyword matching curated annotations.  
  3. Trait  Restrict the returned QTLs to those detected for a particular phenotypic trait.  
  4. Strains  Restrict the returned QTLs to a particular strain. 
  5. Chromosome  Restrict to a particular chromosome,  including start and stop coordinates.
  6. Limit to QTLs with LOD score "greater than __"
  7. Limit to QTLs  with P-value greater than 0 and less than 1  

QTL Search Form

2. QTL Search Form - Provides more customizable options for locating specific QTL information. Details about search parameters are outlined below. (link this to section below)

Quick Guide

  1. http://rgd.mcw.edu/objectSearch/qtlQuery.jsp
  2. Enter the symbol or keyword, then click "Search QTLs".
  3. OR searches can be limited to a particular chromosome and genome start or stop location.
  4. To find all QTLs for a particular trait AND chromosome enter both.
  5. Additional search criteria are available in the "Classic Search" mode.

(LOD = A statistical estimate of the likelihood that a trait is associated with a locus on a chromosome.  A LOD score of three or more is generally taken to indicate that the locus contains genes that influence the trait.  LOD scores of less than 3 can indicate loci that have limited but "true" influence on a trait, eg when a trait is controlled by several genes at several loci, and none of the genes by itself determines the phenotype.)

 

Quick Guide

  1. http://rgd.mcw.edu/objectSearch/qtlQuery.jsp
  2. Enter the symbol or keyword, then click "Search QTLs".
  3. OR searches can be limited to a particular chromosome and genome start or stop location.
  4. To find all QTLs for a particular trait AND chromosome enter both.
  5. Additional search criteria are available in the "Classic Search" mode.

QTL Query Results

Output of the QTL search can be ordered by characteristics such as chromosome, chromosome start and/or stop positions, LOD scores, p-values and other characteristics.  This makes it easy to find the QTL with the highest statistical score (LOD or P-value) on a certain chromosome, or find the QTL nearest the p-terminal in another instance. The QTL symbols are linked to their respective QTL report pages.

QTL Report Page


General

The "General" tab contains most of the information in RGD about the QTL. Some report pages will not display one or more of the subsections.

Symbol:  The approved QTL symbol. This may be different than the symbol used in the article, but all other symbols used for this QTL will be listed in the alias symbol section.

Name: The approved full text name and number of the QTL.

Trait: The measurable phenotypic trait that has been mapped to the QTL. If multiple traits were reported in the article, only the trait with the highest statistical significance will be indicated.

Subtrait: A subcategory of the specified trait, e.g. 'diastolic' for 'blood pressure'. This allows a degree of categorization of QTLs and their traits. A more comprehensive controlled vocabulary is in development.

Method: How the trait was measured.

LOD Score: 'Logarithm of the odds' score, indicating linkage significance of two loci.

P value: The probability of obtaining a test statistic at least as extreme as the one that was actually observed, assuming that the null hypothesis is true.

Variance: A measure of the variability of a set of numbers.

Position: The chromosome and map coordinate position for the QTL in different genome assemblies are provided (three assemblies are shown here), with the source.

Cross Type: The type of cross used to determine the QTL.

Strains Crossed: The strains that were used to determine the QTL. The strain symbols are linked to Strain reports with more details about each strain.

Model: A link to the QTL presented in the GBrowse tool.

Annotation

The Annotation section includes subsections containing ontology annotations assigned to the QTL.  These are organized by ontology type.  Additional subsections contain information about inclusion of the QTL in disease portals and a list of curated references for the QTL.  By default the subsections are closed to facilitate navigation through the page but each can be expanded with a single click anywhere on the brown title bar. Again, some report pages will not display one or more of the subsections.

Candidate Gene Status - Lists candidate genes for the QTL with links to the gene report pages.

Disease Annotations - These annotations represent disease to QTL associations manually curated from the biomedical literature or imported through automated pipelines from OMIM (Online Mendelian Inheritance in Man) or GAD (Genetic Association Database). The terms come from a disease vocabulary (CTD, http://ctdbase.org/) which combines OMIM and MeSH disease vocabularies.  Disease terms followed by the three-letter evidence code IAGP or IED in parentheses indicate that the annotation is supported by data from the species specific to that gene page.

Phenotype Annotations - These annotations represent the association of QTLs with particular phenotypes.  The terms come from the Mammalian Phenotype Ontology (MP) developed at MGI (http://www.informatics.jax.org/, Genome Biol. 6(1):R7. Epub 2005 Dec 15.) The terms are supported by the same group of evidence codes as used for Disease vocabulary annotations.

Experimental Data Annotations - Listed are terms from five different ontologies, with the evidence code IED indicating that they were Inferred from Experimental Data. These terms were used to curate the QTL from the paper(s) originally describing it. If a disease term was used, it will be found in the "Disease Annotations" subsection. Each term links to a Term Annotation Report providing information and links about the reference used, the QTL and the ontology term, including a link to the term ontology report.

References - curated - All references connected to annotations on the QTL report page are listed here. Citations link to RGD Reference report pages which in turn link to PubMed in most cases.  For more information about RGD Reference Reports, click here.

RGD Disease Portals - In the “RGD Disease Portals” subsection, Disease Portals in which the QTL appears are listed as title/image links.  Those title/image links are connected to the same portal page as the first text link shown to the right side of the title/image link.  The text links to the right side of the title/image links list all sections of the portal where the QTL can be found.

Related QTLs - Genetically or interactionally related QTLs are listed, with report page and reference links.

Region

Genes in Region - Lists genes in the RGSC Genome Assembly v3.4 that overlap the region of the QTL, with descriptive information. The data is downloadable and exportable.

Markers in Region - Lists markers in the RGSC Genome Assembly v3.4 that overlap the region of the QTL, with descriptive information. The data is downloadable and exportable.

Position Markers - Flanking markers are listed, with positional and source information, and links to marker report pages. This subsection is shown opened.

QTLs in Region - Lists other QTLs in the RGSC Genome Assembly v3.4 that overlap the region of the QTL, with descriptive information. The data is downloadable and exportable.

Additional Information

External Database - Links to the QTL in other databases such as Entrez Gene are provided.

Nomenclature - A history of the naming of the QTL is shown (not shown here).

RGD Curation Notes - Descriptive curator notes in several categories are listed with reference links.