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iHMMune-align Germine RepertoiresUNSWIg RepertoireThe iHMMune-align IGHV repertoire, also known as the UNSWIg repertoire, is based upon the IMGT repertoire, but classifies all alleles according to the certainty that the reported germline sequences are error free, and according to the likelihood that misalignments to the alleles could occur because of the existence of highly similar alleles. The alignment output indicates the level of aligned genes from the most certain (L1) to the least certain (L4). L5 alleles are sequences that we believe were reported in error, or that have other deficiencies. They are not included in the IGHV Expressed Repertoire. There are 100 of these sequences. A manuscript describing this analysis was published in 2008 (1).Our study also identified a number of previously unreported polymorphisms (1). Until these polymorphisms have been confirmed by genomic sequencing, they are unlikely to be officially recognised, and they are therefore designated ‘putative polymorphisms’. Putative alleles are indicated using a 'p' designation before the allele number in the allele name. IGHV Combined RepertoireThe combined IGHV repertoire is a non-redundant combination of all IGHV genes and alleles from the IMGT reference set (accessed in June 2007) and the VBASE2 database of germline genes. It also includes the iHMMune-align putative polymorphisms. Functional IGHV, pseudogenes and ORFs are included in this repertoire. Each of the reference sets were aligned against each other using the Smith-Waterman algorithm to prevent duplication of sequences from the different naming schemes. Each unique IGHV appears only once in the IGHV combined repertoire and uses the nomenclature of the IGHV-R1 repertoire.IGHD RepertoireThe iHMMune-align IGHD repertoire (IGHD-R1) is based upon our published evaluation of the IMGT repertoire (2). Note that three members of the IGHD1 family are so similar that alignments to one or other of the genes may be uncertain. As IGHD2-2 alleles can not be distinguished with any confidence, alignments to the *01, *02 and *03 alleles are all designated simply as IGHD2-2. We have identified two new putative IGHD gene polymorphisms, IGHD3-10*p03 (2) and IGHD3-16*p03. These putative polymorphisms are included in the iHMMune-align repertoire.IGHJ RepertoireThe iHMMune-align IGHJ repertoire (IGHJ-R1) is the same as the IMGT repertoire. Our published evaluation of this repertoire (2) raises questions about the existence or accuracy of sequences reported for IGHJ3*01, IGHJ4*01, IGHJ5*01 and IGHJ6*01. There is, however, insufficient evidence to warrant the removal of these sequences from the available repertoire.References
1. Wang, Y., Jackson, K. J. L., Sewell, W. A., and Collins, A. M
2008, Many human immunoglobulin heavy-chain IGHV gene polymorphisms have been reported in error , Immunology and Cell Biology,
86: 111-115
2. C. E. H. Lee, Gaeta, B., Malming, H. R., Bain, M. E., Sewell, W. A. and Collins, A, M., 2006, Reconsidering the human immunoglobulin heavy-chain locus: 1. An evaluation of the expressed human IGHD gene repertoire, Immunogenetics, 57(12):917-925, doi:10.1007/s00251-005-0062-5 3. C. E. H. Lee, Jackson, K. J. L., Sewell, W. A. and Collins, A. M., 2006, Use of IGHJ and IGHD gene mutations in analysis of immunoglobulin sequences for the prognosis of chronic lymphocytic leukemia , Leukemia Research, doi:10.1016/j.leukres.2006.10.013 |
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