Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies

Abstract

HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Extensive information is recorded for each variant and mutation, including sequence alterations, biochemical and hematological effects, associated pathology, ethnic occurrence and references. In addition to the regular updates to entries, we report two significant advances: (i) The frequencies for a large number of mutations causing beta-thalassemia in at-risk populations have been extracted from the published literature and made available for the user to query upon. (ii) HbVar has been linked with the GALA (Genome Alignment and Annotation database, available at http://globin.cse.psu.edu/gala/) so that users can combine information on hemoglobin variants and thalassemia mutations with a wide spectrum of genomic data. It also expands the capacity to view and analyze the data, using tools within GALA and the University of California at Santa Cruz (UCSC) Genome Browser.

Figure 1

Query on HbVar for mutation frequencies in different populations. (a) Construction of the query ‘Find all β-thalassemia mutants in the Greek Cypriot population’. Only parts of the query page are shown. The user needs to specify beta0 or beta+ or beta(0 or + unclear) in the ‘Type of Thalassemia’ field and Greek Cypriots in the ‘Ethnic background’ field (the selections required for such a query are highlighted). The query page also allows the user to insert the desired frequency range (5–100% for this example). (b and c) Output from the query. Four different mutations are displayed. The mutation names are hyperlinked to further information. Upon selection of a specific mutant (IVS-II-745 C → G β⁺ for this example), the frequencies of this mutation for different populations/ethnic backgrounds are displayed (depicted in c), together with detailed information on this hemoglobin variant/thalassemia mutation (not shown).

Figure 2

Linking HbVar and GALA databases and the UCSC Genome Browser to examine the spectrum of mutations that cause β-thalassemia. (a) The set of all β-thalassemia mutations collected from HbVar can be exported to GALA, which is used to generate a bar graph (see also text). (b) The graphical output from the query. The number of mutations found at every nucleotide (bin size of 1) is shown on the vertical axis and the chromosomal position in the horizontal axis. The coordinates for the human β-globin gene (HBB) are based on the April 2003 human reference sequence and include 265 bp of the promoter region (bounded by a SnaBI restriction site) through the gene and extending 300 bp beyond exon 3. Note that HBB is transcribed from right to left in this display (CEN to TEL on the short arm of human chromosome 11). A view from the UCSC Genome Browser is added beneath the plot to show landmarks in HBB. (c) The β-thalassemia mutations in the promoter of HBB are exported to the UCSC Genome Browser and viewed along with alignments between human, mouse and rat sequences.