caa a22 4500 467907765 CHVBK 20180406152839.0 cr unu---uuuuu 170328e20060101xx s 000 0 eng 10.1007/s00251-005-0062-5 doi (NATIONALLICENCE)springer-10.1007/s00251-005-0062-5 Reconsidering the human immunoglobulin heavy-chain locus [Elektronische Daten] 1. An evaluation of the expressed human IGHD gene repertoire [C. Lee, B. Gaëta, H. Malming, M. Bain, W. Sewell, A. Collins] We have used a bioinformatics approach to evaluate the completeness and functionality of the reported human immunoglobulin heavy-chain IGHD gene repertoire. Using the hidden Markov-model-based iHMMune-align program, 1,080 relatively unmutated heavy-chain sequences were aligned against the reported repertoire. These alignments were compared with alignments to 1,639 more highly mutated sequences. Comparisons of the frequencies of gene utilization in the two databases, and analysis of features of aligned IGHD gene segments, including their length, the frequency with which they appear to mutate, and the frequency with which specific mutations were seen, were used to determine the reliability of alignments to the less commonly seen IGHD genes. Analysis demonstrates that IGHD4-23 and IGHD5-24, which have been reported to be open reading frames of uncertain functionality, are represented in the expressed gene repertoire; however, the functionality of IGHD6-25 must be questioned. Sequence similarities make the unequivocal identification of members of the IGHD1 gene family problematic, although all genes except IGHD1-14*01 appear to be functional. On the other hand, reported allelic variants of IGHD2-2 and of the IGHD3 gene family appear to be nonfunctional, very rare, or nonexistent. Analysis also suggests that the reported repertoire is relatively complete, although one new putative polymorphism (IGHD3-10*p03) was identified. This study therefore confirms a surprising lack of diversity in the available IGHD gene repertoire, and restriction of the germline sequence databases to the functional set described here will substantially improve the accuracy of IGHD gene alignments and therefore the accuracy of analysis of the V-D-J junction. Springer-Verlag, 2006 Human nationallicence B Cells nationallicence Antibodies nationallicence Repertoire development nationallicence Lee C. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut Gaëta B. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut Malming H. School of Computer Science and Engineering, University of New South Wales, NSW, Australia aut Bain M. School of Computer Science and Engineering, University of New South Wales, NSW, Australia aut Sewell W. Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales, NSW, Australia aut Collins A. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut Immunogenetics Springer-Verlag 57/12(2006-01-01), 917-925 0093-7711 57:12<917 2006 57 251 https://doi.org/10.1007/s00251-005-0062-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-005-0062-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee C. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut NATIONALLICENCE 700 1- Gaëta B. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut NATIONALLICENCE 700 1- Malming H. School of Computer Science and Engineering, University of New South Wales, NSW, Australia aut NATIONALLICENCE 700 1- Bain M. School of Computer Science and Engineering, University of New South Wales, NSW, Australia aut NATIONALLICENCE 700 1- Sewell W. Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales, NSW, Australia aut NATIONALLICENCE 700 1- Collins A. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Australia aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 57/12(2006-01-01), 917-925 0093-7711 57:12<917 2006 57 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer