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HLA Informatics Group

Deputy Director of Immunogenetics

Professor Steven GE Marsh, BSc PhD ARCS

IMGT/HLA sequence database logo

The IMGT/HLA Sequence Database

The IMGT/HLA Sequence Database currently contains 3201 allele sequences. In addition to the physical sequences the database contains detailed information concerning the material from which the sequence was derived and data on the validation of the sequences.

Gene

Number
Alleles Proteins Null Alleles

HLA-A

673

527

46

HLA-B

1077

911

38

HLA-C

360

283

8


HLA-E

9

3

0

HLA-F

21

4

0

HLA-G

36

14

1


HLA-H

12

- -
HLA-J

9

- -
HLA-K

6

- -
HLA-L

5

- -
HLA-P

4

- -
HLA-V

3

- -

Gene

Number
Alleles Proteins Null Alleles

HLA-DRA

3

2

0

HLA-DRB

669

546

8

HLA-DQA1

34

25

1

HLA-DQB1

93

68

1

HLA-DPA1

27

16

0

HLA-DPB1

128

114

2


HLA-DMA

4

4

0

HLA-DMB

7

7

0

HLA-DOA

12

3

1

HLA-DOB

9

4

0


TAP1

7

5

1

TAP2

4

4

0

MICA

64

54

0

MICB

30

19

2

It is now established procedure for authors to submit the sequences directly to the HLA Sequence Database for checking and assignment of an official name prior to publication, this avoids the problems associated with renaming published sequences and the confusion of multiple names for the same sequence. The need for reasonably rapid publication of new HLA allele sequences has necessitated an annual meeting of the WHO Nomenclature Committee for Factors of the HLA System. Additionally we now publish monthly HLA nomenclature updates both in journals and online to provide quick and easy access to new sequence information. Links to the HLA sequences and nomenclature information are given above.

In collaboration with the Imperial Cancer Research Fund (ICRF) and European Bioinformatics Institute (EBI) we have developed an ORACLE database to house the HLA sequences in such a way as to allow users to present complex queries about the sequence, sequence features, references, contacts and allele designations to the database via a graphical user interface over the web. The initial development of this database was been funded by collaborative European Union BIOMED1 (BIOCT930038) and BIOTECH2 (BIO4CT960037) grants awarded to the ICRF as part of the International ImMunoGeneTics (IMGT) databases. The work on the HLA database is done in collaboration with Julia Bodmer (ICRF), James Robinson previously of the ICRF now at the ANRI and Peter Parham of Stanford University. Direct access to the IMGT/HLA Sequence Database is available from the link above.

In addition to the interactive access to HLA sequences alignments and other tools available via the IMGT/HLA database, we release a set of static alignments on this web site. These are updated every three months.

The IMGT/HLA Sequence Database is described in the following paper:

IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex;
Nucleic Acids Research (2003), 31:311-314
available from here

Nucleic Acids Research cover

The Graph below indicates the numbers of antigens and alleles named since the HLA Nomenclature Committee was first formed in 1968, up to the end of June 2008.

Graph showing numcer of alleles named from 1968 to present
Graph showing numbers of antigens and alleles named from 1968 to June 2008

Support for the IMGT/HLA Sequence Database

The work of maintaining and updating the database has been supported in the past by the Imperial Cancer Research Fund, the National Institute of Health, the National Marrow Donor Program (NMDP) and more recently by the Anthony Nolan Trust. Alternate sources of financial support have been sought for the continued maintenance of the database. The Sequence.org initiative at the NMDP has solicited funds from institutions and companies who produce HLA typing reagents, typing systems, and instrumentation or that otherwise utilize these databases in critical components of their business. To learn more about how your business can support the IMGT/HLA Sequence database Web site, please contact: Doug Kingsriter (dkingsri@nmdp.org), The Marrow Foundation.

We are grateful to acknowledge the support of our Lead Sponsor - Histogenetics and the following other sponsors. Current contributors include The Anthony Nolan Trust, American Society for Histocompatibility and Immunogenetics (ASHI), BAG, Biotest, European Federation for Immunogenetics (EFI), Invitrogen, One Lambda, National Marrow Donor Program (NMDP), The Marrow Foundation, Tepnel, Abbott, Innogenetics and Qiagen.

Lead sponsorship:

Histogenetics, click for more info

Further sponsorship:

further sponsorship

IPD-KIR Sequence Database

The IPD-KIR Sequence Database provides a centralised repository for KIR sequences. Killer cell Immunoglobulin-like Receptors or KIRs have been shown to be highly polymorphic at the allelic and haplotypic level. KIRs are members of the immunoglobulin superfamily (IgSF) formerly called Killer cell Inhibitory Receptors. They are composed of two or three Ig-domains, a transmembrane region and cytoplasmic tail which can in turn be short (activatory) or long (inhibitory). The Leukocyte Receptor Complex (LRC) which encodes KIR genes has been shown to be polymorphic, polygenic and complex like the MHC.

KIR logo

IPD-MHC Sequence Database

The IPD-MHC Sequence Database provides a centralised repository for sequences of the major histocompatibilty complex from a number of different species. Through a number of international collaborations IPD is able to provide the MHC sequences of different species. The sequences provided by each group are curated by experts in the field and then submitted to the central database.

Currently the database includes sequence data from Domestic Dogs, Wolves, Coyotes, Non Human Primates, Cattle, Rats, Domestic Cats, Sheep, Fish and Pigs

IPD MHC logo

HSCT Donor/Patient Project

For the past 12 years, the Anthony Nolan Research Institute has co-ordinated a study to investigate the effects of matching or mis-matching a number of different genetic markers on the outcome of haematopoietic stem cell transplants (HSCT) using unrelated donors. This study involves a total of 37 transplant centres throughout the United Kingdom. Over this period we have recruited well over 1500 Anthony Nolan Trust volunteer donors and their respective recipients.

We are utilising the material made available by this project in several studies that have significantly furthered our understanding of the effects of matching HLA at high resolution and in particular the role of the HLA-DPB1 gene. In addition to this, we are now beginning to investigate the role of genes other than HLA on transplant outcome as we believe that there may be a significant contribution when these are taken in to consideration together with HLA typing. There are two projects being undertaken at this time. The first is trying to establish the effects of NOD2/CARD15 gene polymorphisms on the outcome of unrelated donor haematopoietic stem cell transplants, while the second is investigating the role of KIR genes.

Kaplan-Meier Survival plot

HLA Diversity Analysis of the UK Population

The Anthony Nolan Trust maintains a register of around 390,000 potential bone marrow donors, each of whom have been typed for some of their HLA genes. This data set represents an ideal source of information for studying the HLA genetic diversity in the different UK ethnic groups represented in the register. We are undertaking a project to characterise the geographical HLA genetic diversity of the UK population using donors of North European origin. The results of this project are aimed at aiding the recruitment strategies currently used by the Trust, by the identification of regions with higher diversity. This will contribute to the integration of a more diverse register, and so increase the chances of a patient finding a compatible donor.

Additionally, we are participants of the 15th International Histocompatibility and Immunogenetics Workshop, Registry Diversity Group, an international working group whose objective is to establish the standards for the analysis of genetic data from bone marrow registers or similar sources.

Map of phenotypic diversity in the UK

The HLA FactsBook

Steven Marsh, Peter Parham, Linda Barber - presents up-to-date and comprehensive information on the HLA genes in a manner that is accessible to both beginner and expert alike. The focus of the book is on the polymorphic HLA genes (HLA-A, B, C, DP, DQ, and DR) that are typed for in clinical HLA laboratories. Each gene has a dedicated section in which individual entries describe the structure, functions, and population distribution of groups of related allotypes. Fourteen introductory chapters provide a beginners' guide to the basic structure, function, and genetics of the HLA genes, as well as to the nomenclature and methods used for HLA typing. Further information on the HLA FactsBook may be found on the Elsevier site.

facts book