Human genetic bi-allelic sequences (HGBASE), a database of intra-genic polymorphisms.

The Human Genome Project is providing a wealth of information about the human gene repertoire , and promises to furnish a complete genome sequence (and thereby a complete gene catalog) by the year 2005. This enormous output of data is beginning to be complemented by large scale studies designed to uncover normally occurring variations within human gene sequences. Much of this variability is very subtle, often comprises single nucleotide polymorphisms (SNPs) which are ideally compatible with a number of large scale detection procedures. SNPs will be the basis of future highly dense polymorphic marker maps, and those related to known genes can be exploited in genetic association studies aimed at defining the genetic basis of all manner of complex phenotypes, not least disorders such as mental illness, diabetes, cardiovascular disease and cancer. All indications are that 100,000-200,000 human genome SNPs will be identified within the next two years. In light of the above developments, a database of gene based polymorphisms is obviously required. To fulfill this need we have constructed and recently released at http://hgbase.interactiva.de the HGBASE (human genic bi-allelic sequences) database of intra-genic sequence polymorphism. HGBASE is the result of a joint venture between Its primary purpose is to facilitate genotype-phenotype association studies based upon the rapidly growing number of known, gene related, single nucleotide poly-morphisms (SNPs) and other intra-genic sequence variations. Furthermore, HGBASE will help towards the production of a dense SNP map of the human genome, which itself will be a valuable research tool. HGBASE is not designed to include gene 'mu-tations', but instead is a catalog of intra-genic (promoter to transcription end point) sequence variants found in 'normal' individuals. Although the distinction between 'mutation' and 'variation' can be somewhat blurred, the general idea is that the content of HGBASE concerns frequently occurring 'normal polymorphisms', whether or not they are suspected to increase the risk of developing a particular phenotype. This is in contrast to 'mu-tant sequences' which are known to cause genetic disease. Despite its name, HGBASE contains all types of intra-genic variation and is not limited to bi-allelic polymorphisms (though these do represent most of the database content). Both functional polymorphisms (e.g. promoter and non-silent codon changes) and non-functional polymorphisms (e.g. intron sequence differences) are included. This is for two reasons. Firstly, it is often difficult to be certain about the functional consequence of a variation. Secondly, regardless of functional relevance, any intra-genic polymorphism can …