Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow Print PDF (184K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Minoshima, S.
Right arrow Articles by Shimizu, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Minoshima, S.
Right arrow Articles by Shimizu, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research Pages 358-361  

Keio Mutation Database for eye disease genes (KMeyeDB)
Introduction
Database And Software
Accessibility And Availability
Acknowledgements
References

Keio Mutation Database for eye disease genes (KMeyeDB)

Keio Mutation Database for eye disease genes (KMeyeDB)

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 September 21, 1998; Accepted October 5, 1998

ABSTRACT

A database of mutations in human eye disease genes has been constructed. This KMeyeDB employs a database software MutationView which provides graphical data presentation and analysis as a smooth user-interface. Currently, the KMeyeDB contains mutation data of 16 different genes for 18 eye diseases. The KMeyeDB is accessible through http://mutview.dmb.med.keio.ac.jp with advanced internet browsers.

INTRODUCTION

We have been involved in the identification and characterization of the genes responsible for hereditary eye diseases and have so far cloned three novel genes: myocilin (MYOC) (1), retina-specific amine oxidase (AOC2) (2,3) and immunoglobulin superfamily gene containing leucine-rich repeat (ISLR) (4) using the enriched retina cDNA library. Of these, myocilin was found to be identical to the TIGR (Trabecular meshwork-Induced Glucocorticoid Responsive) which was reported to be responsible for the chromosome 1q-linked primary open angle glaucoma (GLC1A) (5,6). Furthermore, we have found various mutations in previously established eye-disease genes in Japanese patients (7-10). To aid efficient DNA diagnosis, we have collected mutation data of the pathogenic genes for a variety of eye diseases including retinitis pigmentosa, glaucoma, corneal dystrophy, choroideremia and others (Table 1).


Table 1. Mutation data in the KMeyeDB

DATABASE AND SOFTWARE

Database was constructed for each gene as a set of hierarchical tables with formats defined in our distributed database software MutationView, which will be described elsewhere (S.Minoshima, S.Mitsuyama, S.Ohno, T.Kawamura and N.Shimuzu, manuscript submitted). Currently, KMeyeDB covers 18 diseases and 16 genes as shown in Table 1. 447 mutations have been collected from 108 literature sources.


Table 2. Mutations of the MYOC gene in primary open angle glaucoma
*1Abbreviations are as follows: M, missense; N, nonsense; P, polymorphism.
*2Elevated intraocular pressure and optic nerve cupping in the presence of a biomicroscopically normal trabecular meshwork.
*3Abbreviations are as follows: AD, autosomal dominant; ND, not described.
*4The description 10.5 (6-27) means that the averaged age is 10.5 years among 6-27 years.

Table 2 shows all the mutation data of the MYOC gene as a typical example of KMeyeDB contents. Using MutationView software, these collected mutation data can be viewed in various ways (Figs 1, 2 and 3). Figure 1 shows a default display of gene structure window, in which each mutation is presented at the proper position of genome structure as a histogram with height proportional to case number. The type of mutation is shown as in the Symbol Table (Fig. 1, inset). It is obvious that mutations are clustered in exon 3. The additional information on each mutation such as Hereditary Pattern, Age of Onset, Ethnic Origin and Author can be obtained by the function Classify (Fig. 2). Mutations can be sorted according to Ethnic Origin (Fig. 2, right). PCR primers to amplify exons are also shown (Fig. 2, top). It is possible to change the genomic structure to cDNA or coding region mode using View Type pulldown menu (data not shown). Zoom-in is easily performed by repeated clicking of the mouse button to gain normal nucleotide sequence. Figure 3, right, shows the result of zoom-in to exon 3 of the MYOC gene. The vertical cursor line points out the G367R mutation and the `G' at nucleotide position 1099 of cDNA. (The nucleotide position +1 is set to the `A' of the start codon ATG.) Clicking the G367R mutation symbol makes the mutation detail window appear (Fig. 3, left), in which normal and mutant nucleotide sequences are shown with the changed bases (G to A) and amino acids (Gly to Arg) highlighted in red. Furthermore, loss or gain of restriction sites is also displayed which is useful for restriction analysis. PCR primer sequences and reaction condition are presented (Fig. 3, right) by clicking primer name (Fig. 3, top). Thus, all the data are presented visually with smooth user-interface.


Figure 1. Myocilin gene mutations shown in MutationView. See text for details.


Figure 2. Classification of the myocilin gene mutation data based on ethnic origin. See text for details.


Figure 3. Myocilin gene mutation in exon 3. See text for details.

The software MutationView for KMeyeDB is designed to manage data as a distributed database, so that any data, if it is collected with the same format and placed on the WWW site, can be made accessible. We are trying to expand the accessible data to other disease gene mutations in collaboration with world-wide locus-specific mutation databases (LSDBs) created by the expert curators for individual disease genes.

ACCESSIBILITY AND AVAILABILITY

Because of its high capability, access to KMeyeDB requires advanced internet browsing software including: (for Macintosh) Internet Explorer 3.0/4.0 + MRJ2.0; (for Windows95/NT) Netscape Communicator 4.03 AWT1.1, Netscape Communicator 4.05 Preview Release 1 (AWT1.1.5), Internet Explorer 3.0 SDK for Java1.5 or Internet Explorer 4.0/later; (for Solaris 2.4 or later of Sparc workstation) Netscape 4.04 JavaAWT1.1 Preview Release 2 or NetScape Communicator 4.05 Preview Release 1 (AWT1.1.5).

KMeyeDB is located at Keio University School of Medicine and is accessible via http://mutview.dmb.med.keio.ac.jp with user ID and password, which are issued after application through the same URL. The software MutationView is made available to the founders and qualified curators of LSDBs on a collaborative basis to establish a world-wide distributed database system for disease gene mutations. For inquiries, contact Shinsei Minoshima (mino{at}dmb.med.keio.ac.jp) or Nobuyoshi Shimizu (shimizu{at}dmb.med.keio.ac.jp).

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.

REFERENCES

1. Kubota,R., Noda,S., Wang,Y., Minoshima,S., Asakawa,S., Kudoh,J., Mashima,Y., Oguchi,Y. and Shimizu,N. (1997) Genomics, 41, 360-369. MEDLINE Abstract

2. Imamura,Y., Noda,S., Mashima,Y., Kudoh,J., Oguchi,Y. and Shimizu,N. (1998) Genomics, 51, 293-298. MEDLINE Abstract

3. Imamura,Y., Kubota,R., Wang,Y., Asakawa,S., Kudoh,J., Mashima,Y., Oguchi,Y. and Shimizu,N. (1997) Genomics, 40, 277-283. MEDLINE Abstract

4. Nagasawa,A., Kubota,R., Imamura,Y., Nagamine,K., Wang,Y., Asakawa,S., Kudoh,J., Minoshima,S., Mashima,Y., Oguchi,Y. and Shimizu,N. (1997) Genomics, 44, 273-279. MEDLINE Abstract

5. Kubota,R., Kudoh,J., Mashima,Y., Asakawa,S., Minoshima,S., Hejtmancik,J.F., Oguchi,Y. and Shimizu,N. (1998) Biochem. Biophys. Res. Commun., 242, 396-400. MEDLINE Abstract

6. Stone,E.M., Fingert,J.H., Alward,W.L.M., Nguyen,T.D., Polansky,J.R., Sunden,S.L.F., Nishimura,D., Clark,A.F., Nystuen,A., Nichols,B.E., Mackey,D.A., Ritch,R., Kalenak,J.W., Craven,E.R. and Sheffield,V.C. (1997) Science, 275, 668-670. MEDLINE Abstract

7. Saga,M., Mashima,Y., Akeo,K., Kudoh,J., Shimizu,N. and Oguchi,Y. (1998) Curr. Eye Res., 17, 332-335. MEDLINE Abstract

8. Mashima,Y., Imamura,Y., Konishi,M., Nagasawa,A., Yamada,M., Oguchi,Y., Kudoh,J. and Shimizu,N. (1997) Am. J. Hum. Genet., 61, 1448-1450. MEDLINE Abstract

9. Saga,M., Mashima,Y., Akeo,K., Oguchi,Y., Kudoh,J. and Shimizu,N. (1994) Ophthalmic Genet., 15, 61-67. MEDLINE Abstract

10. Saga,M., Mashima,Y., Akeo,K., Oguchi,Y., Kudoh,J. and Shimizu,N. (1993) Hum. Genet., 92, 519-521. MEDLINE Abstract

11. Adam,M.F., Belmouden,A., Binisti,P., Brezin,A.P., Valtot,F., Bechetoille,A., Dascotte,J.C., Copin,B., Gomez,L., Chaventre,A., Bach,J.F. and Garchon,H.J. (1997) Hum. Mol. Genet., 6, 2091-2097. MEDLINE Abstract

12. Suzuki,Y., Shirato,S., Taniguchi,F., Ohara,K., Nishimaki,K. and Ohta,S. (1997) Am. J. Hum. Genet., 61, 1202-1204.

*To whom correspondence should be addressed. Tel/Fax: +81 3 3351 2370; Email: shimizu@dmb.med.keio.ac.jp

This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 9 Dec 1998
Copyright©Oxford University Press, 1998.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
S. Minoshima, S. Mitsuyama, S. Ohno, T. Kawamura, and N. Shimizu
Keio Mutation Database (KMDB) for human disease gene mutations
Nucleic Acids Res., January 1, 2000; 28(1): 364 - 368.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Print PDF (184K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Minoshima, S.
Right arrow Articles by Shimizu, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Minoshima, S.
Right arrow Articles by Shimizu, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?