The Mouse Genome Database genotypes::phenotypes.

Abstract

The Mouse Genome Database (MGD, http://www.informatics.jax.org/), integrates genetic, genomic and phenotypic information about the laboratory mouse, a primary animal model for studying human biology and disease. Information in MGD is obtained from diverse sources, including the scientific literature and external databases, such as EntrezGene, UniProt and GenBank. In addition to its extensive collection of phenotypic allele information for mouse genes that is curated from the published biomedical literature and researcher submission, MGI includes a comprehensive representation of mouse genes including sequence, functional (GO) and comparative information. MGD provides a data mining platform that enables the development of translational research hypotheses based on comparative genotype, phenotype and functional analyses. MGI can be accessed by a variety of methods including web-based search forms, a genome sequence browser and downloadable database reports. Programmatic access is available using web services. Recent improvements in MGD described here include the unified mouse gene catalog for NCBI Build 37 of the reference genome assembly, and improved representation of mouse mutants and phenotypes.

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D712–D719
doi:10.1093/nar/gkn886
Nucleic Acids Research, 2009, Vol. 37, Database issuePublished online 3 November 2008
The Mouse Genome Database
genotypes::phenotypes
Judith A. Blake*, Carol J. Bult, Janan T. Eppig, James A. Kadin,
Joel E. Richardson and the Mouse Genome Database Groupy
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA
Received September 28, 2008; Revised October 19, 2008; Accepted October 20, 2008
ABSTRACT
The Mouse Genome Database (MGD, http://www.
informatics.jax.org/), integrates genetic, genomic
and phenotypic information about the laboratory
mouse,a primary animal
human biology and disease. Information in MGD is
obtained from diverse sources, including the scien-
tific literature and external databases, such as
EntrezGene, UniProt and GenBank. In addition to
its extensive collection of phenotypic allele infor-
mation for mouse genes that is curated from the
published biomedical literature and researcher sub-
mission, MGI includes a comprehensive representa-
tion of mouse genes including sequence, functional
(GO) and comparative information. MGD provides
a data mining platform that enables the develop-
ment of translational research hypotheses based
on comparative genotype, phenotype and functional
analyses. MGI can be accessed by a variety of meth-
ods including web-based search forms, a genome
sequence browser and downloadable database
reports. Programmatic access is available using
web services.Recent
described here include the unified mouse gene cat-
alog for NCBI Build 37 of the reference genome
assembly, and improved representation of mouse
mutants and phenotypes.
modelforstudying
improvementsin MGD
INTRODUCTION
The Mouse Genome Database (MGD) is a comprehensive
public resource providing integrated access to genetics,
genomics, functional and phenotypic data for the labora-
tory mouse (1–3). MGD is a core database component of
the Mouse Genome Informatics (MGI) database resource
(http://www.informatics.jax.org). Other resources that are
integrated with MGD as part of the MGI resource include
the Gene Expression Database (GXD) (4), the Mouse
Tumor Biology Database (MTB) (5) and the Gene
Ontology (GO) project (6).
MGD facilitates translational biomedical research via a
comprehensive database resource integrated with bio-
ontological semantic standards that enhances the use of
the laboratory mouse as a model animal system for study-
ing human biology. Primary data types in MGD include
sequences, genetic and physical maps, genes, gene func-
tion, gene families, strains, mutant phenotypes, SNPs,
animal models of human disease and mammalian homol-
ogy. MGD annotations are integrated through a combina-
tion of expert human curation and automated processes.
Examples of vocabularies and ontologies utilized in MGD
include the GO (6), Mammalian Phenotype (MP)
Ontology (7) and the Anatomical Dictionary of Mouse
Development (8). Mouse genes and gene products in
MGD are also associated with multiple other informatics
resources including the Online Mendelian Inheritance in
Man (OMIM), UniProt protein resources and PIR protein
super family classifications. MGI is the authoritative
source for mouse gene and strain nomenclature and GO
functional annotations. MGI is the most comprehensive
public resource of information on mouse phenotypes and
associations between mouse models and human disease.
Data in MGD are updated daily. Data access is accom-
plished via dynamically generated web pages, text files
available via FTP (updated nightly) and through direct
SQL (account is required). In general, there are 4–6
major software releases per year to support access and
*To whom correspondence should be addressed. Tel: +1 207 288 6248; Fax: +1 207 288 6132; Email: jblake@informatics.jax.org
yThe Mouse Genome Database Group: M.T. Airey, A. Anagnostopoulos, R.P. Babiuk, R.M. Baldarelli, M.J. Baya, J.S. Beal, S.M. Bello,
D.W. Bradt, D.L. Burkart, N.E. Butler, J.W. Campbell, L.E. Corbani, S.L. Cousins, D.J. Dahmen, H. Dene, A.D. Diehl, K.L. Forthofer,
K.S. Frazer, D.E. Geel, M.M. Hall, M. Knowlton, J.R. Lewis, I. Lu, L.J. Maltais, M. McAndrews-Hill, S. McClatchy, M.J. McCrossin,
T.F. Meehan, D.B. Miers, L.A. Miller, L. Ni, H. Onda, J.E. Ormsby, D.J. Reed, B. Richards-Smith, D.R. Shaw, R. Sinclair, D. Sitnikov,
C.L. Smith, P. Szauter, M. Tomczuk, L.L. Washburn, I.T. Witham and Y. Zhu.
? 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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display of new data types. A recent summary of MGD
content is shown in Table 1.
2008 IMPROVEMENTS AND UPDATES
New waysto explore mouse phenotypes
The Allele Detail page for each mutant allele in MGI now
includes two distinct views of phenotype data that provide
powerful options for exploring relationships between
genotypes and phenotypes (Figure 1).
In the ‘Phenotype summary’ section of the page, a
matrix view of phenotypes (vertical axis) by genotypes
(horizontal axis) allows users to quickly view the range
of phenotypic effects observed for a given allele. The
effects of different allelic combinations (such as homozy-
gous, heterozygous, conditional and complex) in different
genetic backgrounds can be compared. The general phe-
notype classes can be expanded individually (as shown in
Figure 2A) or all phenotype terms can be viewed or
hidden using the ‘show’/‘hide’ option in the matrix
header. This matrix view can also be used to go directly
to the phenotypic details for a specific genotype (displayed
in a new window) by clicking on its genotype abbreviation
(e.g. hm1, for homozygous 1).
The ‘Phenotypic data by genotype’ section presents
a table of all genotypes involving the allele being viewed.
Each genotype is a link that expands to reveal the full
phenotype details for that genotype, including disease
model associations (Figure 2B). Details for all genotypes
containing the mutant allele can be viewed at once or
hidden using the ‘show’/‘hide’ option in the header of
this section.
A brief Allele Tour (http://www.informatics.jax.org/
faq/Allele_tour.shtml) is available giving an overview of
these changes and a help document further explains the
Phenotypic Allele Detail pages (http://www.informatics.
jax.org/userdocs/allele_detail_report.shtml).
Unified mouse genecatalog
The catalog of mouse genes in MGD serves as the foun-
dation for functional annotation of all genes and genome
features in the MGI database. The MGD gene curation
process integrates gene predictions from Ensembl, NCBI
and Vega into a single, nonredundant catalog. The unified
gene catalog for most recent genome assembly (NCBI
Build 37, or B37) is available from MGD and is updated
when new gene predictions are released.
The concept of gene in the unified mouse gene catalog
refers to the computational prediction of structural
genome features including protein- and nonprotein-
coding genes. The concept of gene in MGD generally
includes the additional concept of heritable phenotype.
That is, cases where an observable trait appears to be
inherited in a typical Mendelian fashion but the under-
lying structural gene is not known.
Build 37 (B37), which includes ?2.6 GB of mouse
sequence, is considered to be ‘essentially complete’.
MGD has the most current B37 data available from
three providers, NCBI, Ensembl and Vega. The MGI
Mouse Genome Sequencing group analyzed the files
from these three sources to produce a unified mouse
gene catalog that established associations between MGI
markers and the updated coordinates. This allows
researchers to obtain a comprehensive list of mouse
genes from a single source and serves as the basis for
functional annotation of genes in the MGI database.
The algorithm for our gene ‘unification’ process has
been described previously (9). Rather than relying on
sequence similarity to determine the equivalency of pre-
dicted genes, our process looks for the genome coordinate
overlap of annotated exons. Combining the gene predic-
tions from NCBI, Ensembl and Vega for B37 we produced
a catalog of over 34000 genes and pseudogenes in the
mouse genome. Although the overlap of genes predicted
by the different groups was significant there are also a
large number of genes and pseudogenes that are unique
to each of the gene prediction processes. For example, the
initial analysis of gene predictions from B37 indicated that
6953 genes were unique to NCBI, 4707 were unique to
Ensembl and 2986 were unique to Vega.
Newweb design and search tool
New web design. Exploring MGI is now assisted with a
navigation bar that appears on each web page. The navi-
gation bar features cascading menus that lead users
quickly to specific search forms and information pages.
The homepage (Figure 3) boasts new major content area
images, leading to specific content pages that, in turn,
provide relevant data access points and FAQs. This new
navigation paradigm improves intuitive navigation of
MGI, providing more visual clues for users and allowing
quick access to the desired MGI pages.
New search tool. Recently, major infrastructure enhance-
ments have made the MGI Quick Search Tool (Figure 4)
a verbose and comprehensive search entre ´ e into MGI
data. The Quick Search now combines nomenclature
and ID searches with searches of MGI annotations
Table 1. Snapshot of data content in MGD: 26 September 2008
MGD data statistics26 September 2008
Genes with nucleotide sequence data
Genes with protein sequence data
Genes (including uncloned mutations)
Genes with gene traps
Mapped genes and markers
Genes with GO annotations
Mouse/human orthologs
Mouse/rat orthologs
Phenotypic alleles
Genes with one or more phenotypic alleles
Phenotypic alleles that are targeted mutations
Genes with targeted mutations
Human diseases with one or more mouse models
QTLs
References
Mouse RefSNPs
Mouse nucleotide sequences integrated into the
MGI system (includes ESTs)
28869
27244
37696
12390
46288
18082
16685
15787
20478
7876
12338
5306
858
3979
133867
10089692
>8750000
Only genes with nucleotide sequence data are included in the unified
gene catalog.
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1
2
Figure 1. Allele detail page for the Engtm1Mletargeted mutation. The ‘Phenotype summary’ section [labeled 1] displays a matrix view of phenotype
terms (vertical axis) by genotypes (horizontal axis). Phenotype terms can be expanded to show more detail and each genotype abbreviation links to a
page detailing the full phenotype for that genotype. The ‘Phenotypic data by genotype’ section [labeled 2] shows a table of genotypes involving
Engtm1Mle. Each genotype can be expanded to reveal full phenotypes. All data for each of the phenotype sections of this page can be viewed using the
‘show’/‘hide’ options in the section headers.
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1
2
A
B
Figure 2. Using the new expansion features for comparing phenotypes. (A) The ‘Phenotype summary’ matrix is shown expanded for the cardio-
vascular system term [labeled 1]. Note the finer granularity of the terms. The genetic background effect in Engtm1Mle/+heterozygotes can clearly be
seen. Heterozygote 4 (ht4) displays a normal cardiovascular phenotype, compared with the other two heterozygous genotypes (ht2, ht3). By glancing
below to the ‘Phenotypic data by genotype’ section [labeled 2], it can be observed that in Engtm1Mle/+mice, the addition of background alleles from
the CD-1 strain appears to confer a protective effect for these cardiovascular system phenotypes. (B) The ‘Phenotypic data by genotype’ section is
shown expanded for one of the genotypes (Engtm1Mle/+heterozygotes in the 129P2/OlaHsd-Engtm1Mlestrain, abbreviated ht2).
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Figure 3. Redesigned MGI Homepage. Notable design items of the new MGI web pages include a navigation bar that is included on every MGI
page, featuring cascading menus that lead users quickly to the query form or information page of interest. On the homepage, clickable images
representing major content areas lead users to pages with additional information, descriptions of MGD data for that area, links to query forms and
reports, and relevant FAQs.
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and ontologies. The combination of an enhanced nomen-
clature search (symbols, names, orthologs), and complete
indexing of MGI data, and weighted word searches pro-
vides an instantaneous return of information, as well as
data for the user on the nature of the returned object. The
Quick Search has become a robust way for those unfami-
liar with MGI to focus their interests and a simplified
search for users who seek quick entry into specific infor-
mation (e.g. give me detail for gene X; what information
does MGI have about retinal degeneration?). Advanced
search forms in MGI continue to support complex queries
such as ‘What genes on Chromosome 11 functions as tran-
scription factors and have mutations associated with
abnormalities of the inner ear?’
COMMUNITY AUTHORITIES AND ACCESS
Mousegene, allele and strainnomenclature
MGD is responsible for assigning official nomenclature to
mouse genes, alleles and strains following the guidelines
set by the International Committee on Standardized
Figure 4. New MGI search tool. The new search tool provides maximum flexibility for quickly locating genes and annotations of interest in MGI.
Searches are automatically done against nomenclature (gene symbols/names, synonyms, orthologs), ontologies/vocabularies used for MGI data asso-
ciations, including gene function, process and cellular location (GO), phenotype (MP) and disease terms (OMIM), anatomical terms, protein domains
(PIRSF) and accession IDs. Results returned are ranked by best match to the term(s) entered by the user and links are provided to the underlying data
and to a comprehensive list of matches in the database. The figure shows the results for searching for: deafness hearing NM_013627. The terms deafness
and/or hearing were matched to 267 genes and 246 vocabulary terms, and the sequence ID retrieved the corresponding RefSeq match.
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Genetic Nomenclature for Mice (http://www.informatics.
jax.org/nomen). MGD staff work with various bioinfor-
matics resource curators to resolve nomenclature incon-
sistencies resulting from regular data exchange of shared
links, and with specialists for human (http://www.genena
mes.org/), rat (http://rgd.mcw.edu) and other species
(e.g. zebrafish http://zfin.org) to provide an organized
approach to the nomenclature process. Collaborative
efforts between the mouse and human nomenclature com-
mittees and scientific experts in specific domain areas pro-
vide an up-to-date analysis and compilation of the latest
knowledge about genes and gene families, such as the
NLR family (10). The MGD group that also assists jour-
nal editors to ensure standardized nomenclature is
adhered to in publications. The MGD nomenclature
coordinator can be contacted
informatics.jax.org).
by email (nomen@
Electronic datasubmission
MGD accepts contributed data sets for any type of data
maintained by the database. The most frequent types of
contributed data are mutant allele and phenotypic infor-
mation originating with the large mouse mutagenesis cen-
ters and repositories that contribute to the International
Mouse Strain Resource (IMSR, http://www.imsr.org).
Each electronic submission receives a permanent database
accession ID. All data sets are associated with their
source, either a publication or an electronic submission
reference. Online details about data submission proce-
dures is found at http://www.informatics.jax.org/mgi
home/submissions/submissions_menu.shtml.
Community outreachand usersupport
MGD user support can be accessed through online doc-
umentation and easy email or phone access to User
Support Staff.
? World Wide Web:http://www.informatics.jax.org/mgi
home/support/support.shtml
? Email access:mgi-help@informatics.jax.org
? Telephone access:1-207-288-6445
? FAX access:1-207-288-6132
Other outreach:MGI-LIST
jax.org/mgihome/lists/lists.shtml) is a moderated and
active email bulletin board supported by the MGD User
Support group.
(http://www.informatics.
HIGH-LEVEL OVERVIEW OF THE MAIN
COMPONENTS AND IMPLEMENTATION
MGD is implemented in the Sybase relational database
management system with approximately 180 tables
within which the biological information is stored.
BLAST-abledatabases,genome
sequence data and image data are stored outside the rela-
tional database. An editing interface (EI) and automated
load programs are used to input data into the MGD
system. The EI is an interactive, graphical application
used by curators. Automated load programs that integrate
larger data sets from many sources into the database
assemblyfilesfor
include quality control (QC) checks and processing algo-
rithms that integrate the bulk of the data automatically
and identify issues to be resolved by curators or the data
provider. Thus, through EI and automated loads, we
acquire and integrate large amounts of data into a high-
quality, knowledgebase.
Public data access is provided through the web interface
(WI) where users can interactively query and download
our data through a web browser. MouseBLAST allows
users to do sequence similarity searches against a variety
of rodent-relevant sequence databases that are built
weekly from selected sequence databases from NCBI,
UniProt and other providers. Mouse GBrowse allows
users to visualize mouse data sets against the genome as
a series of linear tracks. FTP reports are a major source
for other data providers who link to or use MGD data in
their products, and for computational biologists who use
MGD data in their analyses. Programmatic access to
MGD via web services is also available. All MGD files
and programs are openly and freely available.
CITING MGD
For a general citation of the MGD resource please cite this
article. In addition, the following citation format is sug-
gested when referring to datasets specific to the MGD
component of MGI: Mouse Genome Database (MGD),
Mouse Genome Informatics, The Jackson Laboratory,
Bar Harbor, Maine (URL: http://www.informatics.jax.
org). [Type in date (month, year) when you retrieved the
data cited.] Citation, Copyright, Warranty Disclaimer and
other resource-specific information can be found in the
footer of all MGI web pages.
FUNDING
NIH/NHGRI (grant HG000330 to Mouse Genome
Database). Funding for open access charge: HG 000330.
Conflict of interest statement. None declared.
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