V_H replacement footprint analyzer-I, a Java-based computer program for analyses of immunoglobulin heavy chain genes and potential V_H replacement products in human and mouse

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