¹Institute of Medical Technology, University of Tampere, P. O. Box 607, FIN-33101-Tampere, Finland, fax +358-3-215 7710, e-mail ltmavi{at}uta.fi,
²Istituto di Tecnologie Biomediche Avanzate, CNR, via F.lli Cervi, 93, 20090 Segrate (MI), Italy, fax. +39-2-26422660, e-mail villa{at}itba.mi.cnr.it

RAG1 deficiency is an autosomal recessive severe combined immunodeficiency (SCID) caused by mutations in the gene coding for V(D)J recombination activating protein 1 (RAG1). The defect in the V(D)J recombinase machinery can cause either severe combined immunodeficiency without B and T cells (B-T- SCID) or Omenn syndrome (OS). Hereditary immunodeficiency-causing mutations are collected into ImmunoDeficiency mutatation databases (IDbases), which are available at http://www.uta.fi/imt/bioinfo/. IDbases contain mutation data, both published and directly submitted information. For each patient is given following information (when available): The identification of the entry and plain English description of the mutation are followed by reference and formal characterisation of the mutation. Last are the various parameters from the patient.

IDbases are maintained with MUTbase program suite (1), which provides an easy, interactive and quality controlled submission of information to mutation databases. For further study of the databases on the World Wide Web, a number of tools are provided. The program package also writes and updates a large number of Web pages e.g. about distribution and statistics of disease-causing mutations, and changes in restriction patterns.

RAG1 protein comprises 1043 amino acids. It has five basic regions, which are necessary for nuclear localization, a region with homology to the DNA binding domain of bacterial invertases and homeodomain proteins, zinc finger domains, and a zinc binding dimerization motif (2). The RAG1 core domain is sufficient for in vitro biological activity of RAG1 protein. The RAG2 interacting domain, which allows interaction with RAG2, has been mapped to the second half of RAG1 protein.

RAG1base (http://www.uta.fi/imt/bioinfo/RAG1base/) lists 29 mutation entries are from unrelated families showing 34 unique molecular events. The localisation of the mutations on the gene and protein for RAG1 can be analysed by clicking sequences. This can be performed either on genomic, cDNA or amino acid level. Several tables provide information about the distribution of mutations and several clickable pages are related to modifications in restriction pattern. RAG1base provides direct link to the SRS search engine at EBI for further analysis.

About 74 % of mutations are in RAG1 core domain (25 unique molecular events). The frequency is higher than the proportional length of the core domain (59 %). All kinds of mutation types occur in RAG1 protein: 22 missense mutations, 6 nonsense mutations, 5 frameshift deletions, 1 frameshift insertion, and 1 undefined deletion.

References

1. Riikonen, P. and Vihinen, M. (1999) Bioinformatics, (in press).
2. Schwarz, K., Notarangelo, L. D., Spanopoulou, E., Vezzoni, P. and Villa, A. (1999) In Ochs, H. D. (ed.), Primary Immunodeficiency Diseases. A Molecular and Genetic Approach. Oxford University Press, New York, Oxford, pp. 111-20.