Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

Abstract

HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Database records include extensive phenotypic descriptions, biochemical and hematological effects, associated pathology and ethnic occurrence, accompanied by mutation frequencies and references. Here, we report updates to >600 HbVar entries, inclusion of population-specific data for 28 populations and 27 ethnic groups for α-, and β-thalassemias and additional querying options in the HbVar query page. HbVar content was also inter-connected with two other established genetic databases, namely FINDbase (http://www.findbase.org) and Leiden Open-Access Variation database (http://www.lovd.nl), which allows comparative data querying and analysis. HbVar data content has contributed to the realization of two collaborative projects to identify genomic variants that lie on different globin paralogs. Most importantly, HbVar data content has contributed to demonstrate the microattribution concept in practice. These updates significantly enriched the database content and querying potential, enhanced the database profile and data quality and broadened the inter-relation of HbVar with other databases, which should increase the already high impact of this resource to the globin and genetic database community.

Figure 1.

The additions in the updated HbVar query page. Hyperlinks allowing the user to query for genomic variants using the UCSC and PSU Genome Browsers (see also Figure 2), recent additions and/or updates of the HbVar data content and HbVar entries that have links to other databases, such as dbSNP, Swiss-Prot and OMIM (see text for details).

Figure 2.

Overview of the new HbVar visual display feature that couples with the PSU Genome Browser. A user can select a particular gene or genomic region in the human α- or β-globin cluster in the HbVar query page (HBB in this example) and the query returns all genomic variants (base changes, small indels and gross deletions) documented in HbVar that are present within the selected region. Note that the majority of single base changes are nicely clustered within the HBB gene exons. Similar displays can be obtained by using the UCSC Genome Browser using the HbVar custom tracks (not shown). The PSU Genome Browser toolbar is shown on top.

Figure 3.

HBB allele frequency data visualization in FINDbase database. (A) The present query involves all HBB gene variants with an allele frequency between 19.96 and 30.59%. Query returns 30 records sorted by frequency. (B) The user can zoom in to each record (red box) for details [this record involves the HBB:c.93-21G>A allele frequency in the Bulgarian population (24.75%), documented in the data entry displayed in the list on the right (see also 11)].