AUTHOR=Huang Lin , Lange Miles D., Zhang Zhixin 

TITLE=VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse

JOURNAL=Frontiers in Immunology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00040

DOI=10.3389/fimmu.2014.00040

ISSN=1664-3224

ABSTRACT=<p>V<sub>H</sub> replacement occurs through RAG-mediated secondary recombination between a rearranged V<sub>H</sub> gene and an upstream unrearranged V<sub>H</sub> gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3′ end of V<sub>H</sub> gene coding region, a short stretch of nucleotides from the previous rearranged V<sub>H</sub> gene can be retained in the newly formed V<sub>H</sub>–D<sub>H</sub> junction as a “footprint” of V<sub>H</sub> replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through V<sub>H</sub> replacement. To explore the contribution of V<sub>H</sub> replacement products to the antibody repertoire, we developed a Java-based computer program, V<sub>H</sub> replacement footprint analyzer-I (V<sub>H</sub>RFA-I), to analyze published or newly obtained IgH genes from human or mouse. The V<sub>H</sub>RFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential V<sub>H</sub>, D<sub>H</sub>, and J<sub>H</sub> germline genes; then, it searches for V<sub>H</sub> replacement footprint motifs within the V<sub>H</sub>–D<sub>H</sub> junction (N1) regions of IgH gene sequences to identify potential V<sub>H</sub> replacement products; it can also analyze the frequencies of V<sub>H</sub> replacement products in correlation with publications, keywords, or V<sub>H</sub>, D<sub>H</sub>, and J<sub>H</sub> gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified V<sub>H</sub> replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of V<sub>H</sub> replacement products in human and mouse.</p>