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Partitioning of rearranged Ig genes by mutation analysis demonstrates D-D fusion and V gene replacement in the expressed human repertoire.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Jan 01; Vol. 172 (1), pp. 340-8. - Publication Year :
- 2004
-
Abstract
- The accurate partitioning of Ig H chain V(H)DJ(H) junctions and L chain V(L)J(L) junctions is problematic. We have developed a statistical approach for the partitioning of such sequences, by analyzing the distribution of point mutations between a determined V gene segment and putative Ig regions. The establishment of objective criteria for the partitioning of sequences between V(H), D, and J(H) gene segments has allowed us to more carefully analyze intervening putative nontemplated (N) nucleotides. An analysis of 225 IgM H chain sequences, with five or fewer V mutations, led to the alignment of 199 sequences. Only 5.0% of sequences lacked N nucleotides at the V(H)D junction (N1), and 10.6% at the DJ(H) junction (N2). Long N regions (>9 nt) were seen in 20.6% of N1 regions and 17.1% of N2 regions. Using a statistical analysis based upon known features of N addition, and mutation analysis, two of these N regions aligned with D gene segments, and a third aligned with an inverted D gene segment. Nine additional sequences included possible alignments with a second D segment. Four of the remaining 40 long N1 regions included 5' sequences having six or more matches to V gene end motifs, which may be the result of V gene replacement. Such sequences were not seen in long N2 regions. The long N regions frequently seen in the expressed repertoire of human Ig gene rearrangements can therefore only partly be explained by V gene replacement and D-D fusion.
- Subjects :
- Cytosine metabolism
Germ-Line Mutation
Guanine metabolism
Humans
Immunoglobulin Heavy Chains biosynthesis
Immunoglobulin Joining Region biosynthesis
Immunoglobulin Joining Region genetics
Immunoglobulin M biosynthesis
Immunoglobulin M genetics
Immunoglobulin Variable Region biosynthesis
Oligonucleotides biosynthesis
Oligonucleotides genetics
Point Mutation
Probability
Sequence Alignment methods
Antibody Diversity genetics
DNA Mutational Analysis methods
Gene Expression Regulation immunology
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin
Immunoglobulin Heavy Chains genetics
Immunoglobulin Variable Region genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 14688342
- Full Text :
- https://doi.org/10.4049/jimmunol.172.1.340