Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis

Abstract

A core part of the Mouse Genome Informatics (MGI) resource is the collection of mouse mutations and the annotation phenotypes and diseases displayed by mice carrying these mutations. These data are integrated with the rest of data in MGI and exported to numerous other resources. The use of mouse phenotype data to drive translational research into human disease has expanded rapidly with the improvements in sequencing technology. MGI has implemented many improvements in allele and phenotype data annotation, search, and display to facilitate access to these data through multiple avenues. For example, the description of alleles has been modified to include more detailed categories of allele attributes. This allows improved discrimination between mutation types. Further, connections have been created between mutations involving multiple genes and each of the genes overlapping the mutation. This allows users to readily find all mutations affecting a gene and see all genes affected by a mutation. In a similar manner, the genes expressed by transgenic or knock-in alleles are now connected to these alleles. The advanced search forms and public reports have been updated to take advantage of these improvements. These search forms and reports are used by an expanding number of researchers to identify novel human disease genes and mouse models of human disease.

Fig. 1

MGI allele detail page for Spns2 ^{tm1b(KOMP)Wtsi} Information available includes a Nomenclature, mutation origin, project collection, and molecular details, when available, phenotype data, IMSR data for location of this mutation in a public repository, references. b Phenotype detail viewed by clicking on the toggle for “hematopoietic system.” c Section of the Marker detail page for Spns2 showing all known mutations for that gene, other genomic mutations including Spns2, incidental mutations found in genome wide sequencing, a short phenotype summary and links to image and disease data

Fig. 2

MGI allele detail page for Gt(ROSA)26Sor ^{tm1(Kcnj11*V59M)Fmas} shows annotation of the expressed component of this knock-in allele and a molecular image showing integration details. A mutated form of the mouse Kcnj11 gene is expressed from the endogenous Gt(ROSA)26Sor promoter after Cre-mediated recombination

Fig. 3

MGI allele detail page for Cm shows annotation of the endogenous genes mutated by this large deletion. In the mutation description section the first 3 genes are shown with a link that opens another window showing the full list of genes and additional information on how the gene is modified by the mutation. Note, at the bottom of the page is a section showing the human diseases modeled by mice carrying the Cm mutation

Fig. 4

The MGI Genes & Markers Query now features an improved Phenotype/Disease search tool. When terms are selected from the “Select Anatomical Systems Affected by Phenotypes” tool the term name and ID are shown next to the search box. Searches may combine multiple MP or OMIM terms using Boolean operators. Results of a search may be downloaded, forwarded to the batch query, or exported to MouseMine

Fig. 5

The MGI Phenotypes, Alleles & Disease Models Search now features an improved Phenotype/Disease search tool and the ability to search by allele Generation Method, Attributes, and/or Project Collections. In the Phenotype/Disease search box MP and OMIM disease terms may be connected with Boolean operators as on the Genes & Marker Query. Searches can combine terms in the Phenotype/Disease search box with selected Generation Method and/or Allele Attributes. Results of the search may be downloaded as a text or Excel file

Fig. 6

Results of an MGI quick search for “albin*”. a The Genome Features section includes both genes and alleles where the symbol or name matches the search and genes and alleles that are annotated to a matching vocabulary term. b The Vocabulary Terms section includes links to matching MP, OMIM, GO and other vocabulary terms along with links to annotations to each term in MGI