Release 8.9

Human polymorphisms: juggling with health and disease

Recent advances in genomics and proteomics promise to give new insights into the molecular mechanisms of diseases and hopefully will lead to the discovery of novel treatments. The integration of phenotype descriptions along with sequence data, genetic information, as well as physiological, biochemical and structural knowledge may help understand the chain of events leading from a molecular defect to a pathology. In this context, UniProtKB/Swiss-Prot provides the scientific community with a wealth of information on genetic diseases, disease-linked variants and polymorphisms.

In the current release, over 2,000 human entries contain a disease description in the comment section under the topic "involvement in disease". The disease description is short, but it is supplemented with links to the OMIM database, allowing the retrieval of more detailed information about genetic disorders. Additional links to gene-specific databases can be found under web resources.

At the sequence level, close to 28,500 human single amino acid polymorphisms (SAPs) are described, more than half of which are associated with a disease state and about 30% are linked to the Single Nucleotide Polymorphism database (dbSNP). SAPs are described in the feature table and characterized by a unique identifier (FTId), which gives access to the variant web pages. These pages display a synopsis of relevant information for a given variant, including references, sequence context, as well as residue conservation throughout evolution and structural data, when available (example). Mutations that cause major changes to a protein sequence (as is the case for most frameshift mutations) are not and will not be considered to be relevant to UniProtKB/Swiss-Prot, as their deleterious effects on a given protein function is usually obvious.

Finally, our medical annotation effort also consists of the creation of keywords to allow easy retrieval of proteins involved in complex disorders and genetically heterogeneous diseases.

Currently about 100 "medical" keywords have been created, and the list is growing.