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

University of Crete, Retimo, Crete, Greece
Nucleic Acids Research (Impact Factor: 9.11). 02/2004; 32(Database issue):D537-41. DOI: 10.1093/nar/gkh006
Source: PubMed


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 β‐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 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.

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Available from: George Patrinos, Jul 23, 2014
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    • "One-hundred and fifty-eight such mutations are currently reported ( bin/hbvar/query_vars3, accessed 29 June 2015; Patrinos et al., 2004), and many of these can be found on more than one genetic background (Table 2) (Trabuchet et al., 1991; Weatherall and Clegg, 2001a). The precise spatial patterns exhibited by β S -and β 0 -thalassaemia haplotypes are markedly different. "
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    ABSTRACT: The malaria-protective β-globin polymorphisms, sickle-cell (β(S)) and β(0)-thalassaemia, are canonical examples of human adaptation to infectious disease. Occurring on distinct genetic backgrounds, they vary markedly in their patterns of linked genetic variation at the population level, suggesting different evolutionary histories. β(S) is associated with five classical restriction fragment length polymorphism haplotypes that exhibit remarkable specificity in their geographical distributions; by contrast, β(0)-thalassaemia mutations are found on haplotypes whose distributions overlap considerably. Here, we explore why these two polymorphisms display contrasting spatial haplotypic distributions, despite having malaria as a common selective pressure. We present a meta-population genetic model, incorporating individual-based processes, which tracks the evolution of β-globin polymorphisms on different haplotypic backgrounds. Our simulations reveal that, depending on the rate of mutation, a large population size and/or high population growth rate are required for both the β(S)- and the β(0)-thalassaemia-like patterns. However, whilst the β(S)-like pattern is more likely when population subdivision is high, migration low and long-distance migration absent, the opposite is true for β(0)-thalassaemia. Including gene conversion has little effect on the overall probability of each pattern; however, when inter-haplotype fitness variation exists, gene conversion is more likely to have contributed to the diversity of haplotypes actually present in the population. Our findings highlight how the contrasting spatial haplotype patterns exhibited by β(S) and β(0)-thalassaemia may provide important indications as to the evolution of these adaptive alleles and the demographic history of the populations in which they have evolved.
    Full-text · Article · Sep 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    • "Most of them are point mutations localized along the b-globin gene, while only 31 have been reported within the promoter region ( (Giardine et al., 2007, 2014; Patrinos et al., 2004). Their clinical consequences vary from severe b 0 -thal to mild forms of thalassemia intermedia. "
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    ABSTRACT: Different thalassemia mutations have been reported in various ethnic groups and geographical regions in Tunisia. In the present study, we have investigated two rare β(+) -thalassemia mutations, that have not previously been reported in the Tunisian population [β -56 (G > C); HBBc. -106 G > C] and [β -83 (G > A); HBBc. -133 G > A]. The whole β-globin gene was directly sequenced, and haplotype analysis was conducted through a PCR/RFLP method. Results: Two new mutations were identified for the first time in Tunisia. They are located within the promoter region of β-globin gene at position -56 (G > C) and -83 (G > A). Linkage analysis using β-globin gene cluster haplotypes showed that these two mutations were associated with Mediterranean β-haplotype IX [- + - + + + +] and framework 2 (FW2) [CCTCT]. The two newly described mutations lead to the β(+) -thalassemia among Tunisian patients. The haplotype analysis and framework assignment have helped to identify the chromosomal background associated with these mutations, and determine their origin and spread. Am. J. Hum. Biol., 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · American Journal of Human Biology
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    • "Although such variations are available through the LOVD Globin Gene Server [22], the globin-related information offered by the latter is only a subset of that stored on HbVar. Moreover and despite recent improvements [23]–[25], the interface functionality, scope for the integration of additional data and user-friendliness of either platform are limited. In particular, incorporation of laboratory, clinical and epidemiological with molecular data is needed to create an integrated resource that could bridge the gap between genetic analysis and clinical practice. "
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    ABSTRACT: Inherited haemoglobinopathies are the most common monogenic diseases, with millions of carriers and patients worldwide. At present, we know several hundred disease-causing mutations on the globin gene clusters, in addition to numerous clinically important trans-acting disease modifiers encoded elsewhere and a multitude of polymorphisms with relevance for advanced diagnostic approaches. Moreover, new disease-linked variations are discovered every year that are not included in traditional and often functionally limited locus-specific databases. This paper presents IthaGenes, a new interactive database of haemoglobin variations, which stores information about genes and variations affecting haemoglobin disorders. In addition, IthaGenes organises phenotype, relevant publications and external links, while embedding the NCBI Sequence Viewer for graphical representation of each variation. Finally, IthaGenes is integrated with the companion tool IthaMaps for the display of corresponding epidemiological data on distribution maps. IthaGenes is incorporated in the ITHANET community portal and is free and publicly available at
    Full-text · Article · Jul 2014 · PLoS ONE
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