About The Database

BACKGROUND

The Human Intermediate Filament Database was initiated by the Human Genetics Unit, University of Dundee in 2001 and was revised by the Centre for Molecular Medicine and the Bioinformatics Institute in Singapore in 2006, from where it is now being curated (contact us).

Intermediate filaments are part of the cytoskeleton, the flexible scaffold of polymeric filaments in the cytoplasm that is essential for structural integrity of the cell. Intermediate filament proteins are encoded by a large multigene family with an estimated 70 genes in the human genome plus a small number of alternatively spliced transcripts. Six classes of intermediate filament have been described, the two largest of which are the keratins (type I and type II intermediate filaments).

Since 1991, variations in 21 different epithelial keratin genes have been shown to cause of a variety of human diseases in epidermal and epithelial structures. The number of published variants within the keratins alone is now in excess of 1148 and combined with the pathogenic variants that are emerging in the other members of the intermediate filament gene superfamily, this shows the growing need for a readily accessible database of intermediate filament variants. In accordance with the aims of the HUGO Human Genome Variation Society, the Human Intermediate Filament Database has been established to address this need.

The Intermediate Filament Database will function as a continuously updated review of the intermediate filament field and it is hoped that users will contribute to the development and expansion of the database on a regular basis. Contributions may include novel variants, new patients with previously discovered sequence and allelic variants. Suggestions on ways to improve the database are also welcome.

USING THE DATABASE

The entire database can be searched through the "Browse" and "Search" options. A number of different parameters can be used to search the database including unique identifier, intermediate filament, disease DNA variations, amino acid variations, domain, date accepted, author and abstract. Output from the search is returned in a table containing all the pertinent cross referenced information.

Multiple sequence alignment can also be performed via the CLUSTALW program to determine cDNA or protein sequence conservation.

The database is linked to multiple other resources including NCBI RefSeq, PDB, OMIM, UCSC genome browser, NCBI Gene, HomoloGene, PubMed and HGNC. In the case of HGNC, reciprocal links are also available from HGNC that links to Human Intermediate Filament Database. Due to the protein centric nature of the Human Intermediate Filament Database and the gene centric nature of HGNC, a HGNC record will potentially link to multiple records in this database due to the presence of alternative splicing. In such an event, the Human Intermediate Filament Database will present to the user a list of all the protein records resulting from the HGNC gene record. The database uses Jalview and Jmol applets for the visualization of multiple sequence alignment and structure respectively.

The database contains information on disease phenotypes of a variety of different intermediate filament related diseases.

The database has been used by researchers from over 116 countries worldwide since the initial release of the database in June 2006. The following table gives the list of top ten unique countries that have accessed our database.

NOTES ON NOMENCLATURE AND MODIFICATIONS OF PUBLISHED SEQUENCE ANNOTATIONS

The Human Intermediate Filament Database follows the nomenclature suggested by Dunnen, J. T. and Antonarakis, S. E. in their publication: “Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion”, Human Mutation, Volume 15, Issue 1, 2000. Pages: 7-12. For further information on approved gene nomenclature and symbols see Guidelines for Human Gene Nomenclature (1997) by Sue Povey of the HUGO Gene Nomenclature Committee (HGNC). The new keratin nomenclature is used according to Schweizer et al 2006, J. of Cell Biol., Volume 174, Issue 2, 2006. Pages: 169-174. A wide variety of links to other resources on the web can be found at the Useful Links Page.

Users may find some discrepancies between descriptions of some variants in the previously published data and the description presented in the Database. This is mainly due to differences between the nomenclature system used by the original author and the current nomenclature consensus guidelines recommended by Human Genome Variation Society (HGVS) as followed in the generation of the Database. Another possibility is the use of a different reference sequence when describing the variant. The Database uses NCBI RefSeq sequences as the reference sequences. However if an author feels that an error has been made in the representation of their work in the Database, please contact us as soon as possible so that the problem can be quickly addressed.

Last modified: September 06 2007 15:43:02.