VH replacement footprint analyzer-I, a Java-based computer program for analyses of immunoglobulin heavy chain genes and potentia VH 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 VH replacement. Such footprints can be used as markers to identify Ig heavy chain (lgH) 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(H)RFA-I), to analyze published or newly obtained IgH genes from human or mouse. The V(H)RFA-1 program has multiple functional modules: it first uses service provided by the IMGTN-QUEST program to assign potential V-H, D-H, and J(H) germline genes; then, it searches for V-H replacement footprint motifs within the V-H-D-H 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, D-H, and J(H) 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.