The Phenotypes, Alleles & Disease Models project in MGI enables comparative phenotype analysis, searches for human disease models, and hypothesis generation by providing access to spontaneous, induced, and genetically engineered mutations and their strain-specific phenotypes.

Alleles

A primary objective for MGI is the maintenance of a complete catalog of phenotypic mutations in the laboratory mouse. These include spontaneous, induced, and genetically engineered mutations (targeted knockouts and conditionals, transgenics, Cre-constructs, targeted reporters, gene traps, transposon-induced mutations, etc.).

MGI serves as the international authoritative source for nomenclature for mouse alleles, and maintains a complete list of allele symbols, names, and synonyms, each with a unique accession ID. Researchers are encouraged to submit new alleles to reserve symbols and obtain accession IDs prior to publication.

Alleles can be searched within MGI by name or symbol, category (e.g. targeted knockout), genome location, associated phenotypes and disease models using the Phenotypes, Alleles & Disease Models Query Form and a complete listing of alleles can be downloaded from the ftp site (http://www.informatics.jax.org/downloads/reports/index.html#pheno).

Phenotypes

Phenotypes are the manifestation of an individual's genotype in its environment. In the most straightforward case, phenotypic effects of allelic mutations are observed in relation to a control strain background; and the environment within the observing laboratory is considered constant.

Complications quickly expand when considering complex, multi-genic mutations, conditional and tissue-specific allele ablation, the combination of mutations in multiple genes in a single animal, the use of multiple strain backgrounds on which mutations are created and/or transferred, and the experimental application of additional environmental variables that can heighten or lessen phenotypic outcome. To maximize the usefulness of these complex data, phenotypes in MGI are associated with specific genotypes (combinations of allelic mutations on specific genetic backgrounds).

Phenotypes are described in MGI using the Mammalian Phenotype Ontology, a structured vocabulary that allows consistent annotation of mouse genotypes with standard phenotype terminology and associates each piece of phenotypic data with its source (e.g., published literature, large-scale mutagenesis centers, individual research laboratories).

The Phenotypes, Alleles & Disease Models Query Form allows users to ask broad or specific questions about phenotypes of specific mutations or search genome-wide for all genotypes what produce one or a combination of phenotypes.

QTL

QTL are quantitative trait loci, defined by the association of phenotypic characteristics with chromosomal regions. Generally many such loci contribute to quantitative characters, such as body metrics (e.g., length, adiposity), substance preference/aversion (e.g., to alcohol, cocaine), autoimmunity and susceptibility to infection, etc. Recently some QTL have been identified with their underlying genes. MGI captures information on strain-specific QTL variants, including genome location, descriptions of mapping analysis and significance scores, and descriptions of phenotypes using Mammalian Phenotype Ontology terms. QTL can be searched in the same way as other phenotypic alleles.

Models of Human Disease

The primary goal of MGI is to facilitate the use of mouse as a model for human biology and disease. Mouse genotypes that have been used to study specific human diseases are curated in MGI using disease terms found in the Disease Ontology (DO). Within MGI, users can browse for a specific human disease term using the Disease Ontology Browser and follow links to gene and mouse model details.

The Human - Mouse: Disease Connection site provides a path into mouse genetic and comparative data from the human or mouse perspective. Users can begin to explore data by searching for genes (symbols, names, IDs) or genome locations from human or mouse, or by searching with mouse phenotype or human disease terms.

In addition, one can use the Phenotypes, Alleles & Disease Models Query Form to search for diseases in combination with specifying one or more mouse phenotype terms and/or limiting one's search to specific categories of mutant alleles and/or specific genome regions.

All allele, phenotype, and human disease model data are fully integrated with the rich genetic, genomic, and biological data in MGI.