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. 2020 Jan 8;48(D1):D948-D955.
doi: 10.1093/nar/gkz950.

IPD-IMGT/HLA Database

James Robinson  1   2 , Dominic J Barker  1 , Xenia Georgiou  1 , Michael A Cooper  1 , Paul Flicek  3 , Steven G E Marsh  1   2
Affiliations

IPD-IMGT/HLA Database

James Robinson et al. Nucleic Acids Res. .

Abstract

The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.

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Figures

Figure 1.
Figure 1.
The number of HLA alleles named by the WHO Nomenclature Committee for Factors of the HLA System and included in the IPD-IMGT/HLA Database, show a continuous increase in new alleles identified both for class I and class II over the past 30 years. The rate of discovery of new alleles continues to increase with the use of next-generation sequencing technologies, with more new alleles named in the first three months of 2019, than were named in the last century.
Figure 2.
Figure 2.
The IPD-IMGT/HLA Database receives submissions from over 46 countries. The figure shows the location of submitters to the database and the volume received from each country. It should be noted that the source material may be derived from a number of additional countries, and only the location of the submitting laboratory is shown on the map.
Figure 3.
Figure 3.
The IPD-IMGT/HLA Database has received over 53,000 submissions since its launch in 1998. This figure shows the number of submissions annually as well as a breakdown of how the type of submissions has changed with the incorporation of new technologies. Panel A represents HLA class I submissions and panel B represents HLA class II submissions. The advent of technologies capable of routinely sequencing the length of the class I genes, ∼3500 bp, has led to an increase in the number of full-length (5′ UTR to 3′ UTR) submissions, compared to partial submissions covering just exons 2–3, that were previously the norm. The HLA class II introns are substantially longer, and whilst more genomic sequences have been received, the shorter partial sequences, covering just exon 2, still form the majority of submissions.
Figure 4.
Figure 4.
Growth in the number of recognized class I and class II alleles across different typing and sequencing technologies, adapted from Robinson et al. (30).
Figure 5.
Figure 5.
A graphical representation of the variation seen in the HLA-A sequences. Moving from the perimeter towards the centre of the diagram, the outer ring represents the different regions, with the exons filled in blue and numbered, the gDNA positions are also shown. The next layer represents the percentage of alleles with sequence in the database, the further towards the centre, the higher the percentage of alleles with sequence, note exons 2 and 3 where this sequence is mandatory for acceptance in the database. The penultimate inner ring represents the numbers of bases, (A, C, G, T or an indel) seen at each position with the baseline representing a monomorphic position. The final inner ring shows in red, the frequency of the second most common base at each position. The diagram can therefore be seen to show that whilst variation is highest in exons 2 and 3, it is not limited to these regions and there are clear regions of conserved variation throughout the gene.
See this image and copyright information in PMC

References

    1. Robinson J., Malik A., Parham P., Bodmer J.G., Marsh S.G.E.. IMGT/HLA database–a sequence database for the human major histocompatibility complex. Tissue Antigens. 2000; 55:280–287. - PubMed
    1. Ruiz M., Giudicelli V., Ginestoux C., Stoehr P., Robinson J., Bodmer J., Marsh S.G.E., Bontrop R., Lemaitre M., Lefranc G. et al.. IMGT, the international ImMunoGeneTics database. Nucleic Acids Res. 2000; 28:219–221. - PMC - PubMed
    1. Robinson J., Waller M.J., Parham P., Bodmer J.G., Marsh S.G.E.. IMGT/HLA Database–a sequence database for the human major histocompatibility complex. Nucleic Acids Res. 2001; 29:210–213. - PMC - PubMed
    1. Robinson J., Waller M.J., Parham P., de Groot N., Bontrop R., Kennedy L.J., Stoehr P., Marsh S.G.E.. IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res. 2003; 31:311–314. - PMC - PubMed
    1. Robinson J., Marsh S.G.E.. The IMGT/HLA database. Methods Mol. Biol. 2007; 409:43–60. - PubMed

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