Download Keio Mutation Database (KMDB) for human

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Nucleic Acids Research, 2000, Vol. 28, No. 1
© 2000 Oxford University Press
Keio Mutation Database (KMDB) for human disease
gene mutations
Shinsei Minoshima, Susumu Mitsuyama, Saho Ohno, Takashi Kawamura and
Nobuyoshi Shimizu*
Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku,
Tokyo 160-8582, Japan
Received October 12, 1999; Accepted October 13, 1999
ABSTRACT
A database of mutations in human disease-causing
genes has been constructed and named as Keio
Mutation Database (KMDB). This KMDB utilizes a
database software called MutationView which was
designed to compile various mutation data and to
provide graphical presentation of data analysis.
Currently, the KMDB accommodates mutation data
of 38 different genes for 35 different diseases which
are involved in eye, heart, ear and brain. These
KMDBs are accessible through http://mutview.dmb.
med.keio.ac.jp with advanced internet browsers.
INTRODUCTION
We have previously developed the database software,
MutationView, as a prototype for distributed database systems
(S.Minoshima, S.Mitsuyama, S.Ohno, T.Kawamura and
N.Shimizu, manuscript submitted). Using MutationView, we
have collected mutation data for human eye disorder genes and
constructed an eye disorder-specific database, KMeyeDB (1).
Here, we further utilized MutationView for other human
diseases involved in heart, ear and brain. Mutation data related
to cancer and autoimmunity was also developed separately.
These mutation databases were designated KMheartDB,
KMearDB, KMbrainDB and KMcancerDB, respectively, and
integrated as components of MutationView. Thus, MutationView
should be of great use as a central system for a distributed database for locus-specific databases (LSDB) while maintaining
the independency of each LSDB.
DATABASE AND SOFTWARE
Database was made for each gene as a set of hierarchical tables
according to the format defined for the distributed database
software MutationView. MutationView has two different
versions, JAVA and HTML. The former provides a dynamic
interactive user interface and can be used through advanced
browser software with JAVA1.1, while the latter may be used
on conventional browsers and is convenient for downloading
the data.
To date, we have constructed five separate KMDBs in which
a total of 1593 entries of mutations are found for 38 different
genes which are involved in 35 distinct diseases collected from
311 literatures (Table 1).
Table 1. Mutation data in the KMDBs and MutationView
Category
No. of
diseases
No. of
genes
Eye
No. of mutation No. of literatures
entries
compiled
20
17
580
136
Brain/Nerve
3
5
169
58
Heart
4
5
44
13
Ear
2
5
20
7
Autoimmunity
2
2
96
14
Cancer-related
4
4
684
83
35
38
1593
311
Total
Figure 1 upper panel shows the entrance windows of
MutationView and five separate KMDBs. Figure 1 lower panel
shows ‘Anatomy’ window of the JAVA version of MutationView (left), KMeyeDB (center) and KMheartDB (right). By
clicking a certain anatomical part in these windows, a list of
genes and/or diseases associated with eye or heart appear (not
shown). Clicking one of these genes/diseases, ‘myosin binding
protein, cardiac; MYBPC3’ in the KMheartDB creates a ‘Gene
structure’ window, displaying mutation data of the gene
MYBPC3 (Fig. 2, left background). By clicking ‘About this
gene’ button, a window with the same name appears (Fig. 2,
left foreground), showing further information from other databases such as OMIM, GDB and HGMD.
In the default of the ‘Gene structure’ window, mutations are
displayed along the genomic structure of the gene. Various
types of mutations are listed in the ‘Symbol table’ (Fig. 3,
upper right) which pops-up through the help menu. Each
mutation symbol on the X-axis locates exactly on the mutation
site. The height of each bar represents the case number of
mutation that appeared in the literature. Clicking the mutation
symbol ‘1091-2A G’ for example (blue arrow) opens a new
window for the details of mutation (Fig. 2, upper right),
including the change in nucleotide sequence and its consequences
such as alterations of amino acid, splicing signal and restriction
site. In a case that the mutation is a large deletion and complicated
chromosome translocation, schematic diagrams of the mutation
are presented (Fig. 3, bottom, left and right). By clicking the
*To whom correspondence should be addressed. Tel/Fax: +81 3 3351 2370; Email: [email protected]
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Figure 1. Entrance displays of MutationView and five types of KMDBs. See text for details.
‘Zoom-in’ button of the ‘Gene structure’ window, the X-axis
can be changed from the genomic structure to even the nucleotide
sequence (data not shown).
A variety of information can be shown on the Y-axis. These
include mutation frequency, mutation type, symptoms, ethnic
origin, hereditary pattern, onset age, and so on. By clicking the
‘Classify menu’ button, ‘Classify’ window pops-up (Fig. 4,
upper right). Selecting the ‘Mutation type’ and then clicking
the ‘Classify’ button displays a re-classified view in the gene
structure window (Fig. 3, upper left).
Figure 4 displays a result of re-classification of Parkin gene
(PARK2) (2) mutations according to ‘Ethnic origin’. Probe
information such as PCR primers can be displayed in the ‘Gene
structure’ window by switching ‘View type’ menu (Fig. 4,
left). Clicking the ‘PCR primer name’ (indicated by an arrow)
creates a new window, displaying detailed information such as
primer sequences and reaction conditions (Fig. 4, bottom
right).
ACCESSIBILITY AND AVAILABILITY
Since MutationView and the KMDBs employ the JAVA1.1
interpreter for their full function, advanced internet browsing
software is required. These requirements depend on the types
of terminal computers:
• For Macintosh: Internet Explorer 3.0/4.0/4.5 + MRJ2.0/2.1.
• For Windows95/98/NT: Netscape Communicator 4.03 AWT1.1,
Netscape Communicator 4.05 Preview Release 1 (AWT1.1.5),
Netscape Communicator 4.06 or later, Internet Explorer 3.0
with SDK for Java 1.5 or Internet Explore 4.0 or later.
• For Solaris 2.4 or later of SparcWorkstation: Netscape 4.04
JavaAWT1.1 Preview Release 2 (CDE or Open Windows),
Netscape Communicator 4.05 Preview Release 1 (AWT1.1.5)
(Open Windows), or Netscape Communicator 4.06 or later
(Open Windows).
MutationView and the KMDBs are located at Keio University
School of Medicine and are accessible via http://mutview.dmb.
med.keio.ac.jp . The user ID and password are issued after
receiving applications through the same URL. The software
MutationView is available to all interested research groups
under the conditions that users participate actively in the
establishment of a world-wide distributed database system for
disease gene mutations. For inquiries, contact Shinsei Minoshima
([email protected] ) or Nobuyoshi Shimizu (shimizu@
dmb.med.keio.ac.jp ).
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Figure 2. Gene structure window and mutation details of the MYBPC3 gene in the KMheartDB. See text for details.
ACKNOWLEDGEMENTS
We thank Chi Co., Ltd for their extensive collaboration. This
work was supported in part by a fund for the ‘Research for the
Future’ Program from the Japan Society for the Promotion of
Science (JSPS) and a Grant-in-Aid for Scientific Research on
Priority Areas from the Ministry of Education, Science, Sports
and Culture of Japan. The figure of the human body in Figure 1
lower left window was used with publisher’s permission from
‘Cystic Fibrosis’ authored by Michael J. Welsh and Alan E.
Smith in Nikkei Science (1996) Vol. 26, p. 92.
REFERENCES
1. Minoshima,S., Mitsuyama,S., Ohno,S., Kawamura,T. and Shimizu,N.
(1999) Nucleic Acids Res., 27, 358–361.
2. Kitada,T., Asakawa,S., Hattori,N., Matsumine,H., Yamamura,Y.,
Minoshima,S., Yokochi,M., Mizuno,Y. and Shimizu,N. (1998) Nature,
392, 605–608.
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Figure 3. Classified view of gene mutations in the choroideremia shown in the KMeyeDB. Mutations are classified according to mutation type, particularly
chromosome translocation (red arrow) and large deletion (blue arrow).
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Figure 4. Classified view of the Parkin gene mutations and PCR primer information in the KMbrainDB. Mutations are classified according to ethnic origin and the
PCR primer information is displayed for the mutation indicated by an arrow. See text for details.