Molecular characterization of the VH repertoire in Canis familiaris

The immunoglobulin heavy chain variable region in vertebrates is composed of many genes. However, the gene number and the extent of diversity among the VH gene segments vary with the species. To gain insight into the dog VH repertoire, we analyzed its genome sequence. Eighty VH, six DH and three JH segments were mapped to a 1.28Mb region of the dog chromosome 8. Forty-one of these VH genes were potentially functional, and 39 were pseudogenes. The sequence similarity analysis suggests that the dog IgH locus harbors three VH gene families, VH1 (including 76 members), VH2 (including 3 members) and VH3 (including one member), that are classified into mammalian clan III, I and II, respectively. Subsequently, 111 cDNA positive clones from dog 26 mu, 22 gamma, 23 alpha, 16 delta and 24 epsilon chains containing almost full-length VH, DH and JH segments were selected at random. All of the sequences, except for clone G6, which belonged to the dog VH2 family, originated from the dog VH1 family. The germline segments, VH62 (human VH3-21 homology) and VH44 (human VH3-23 homology), seemed to be preferentially used. Our results suggest that the dog VH repertoire appears to be derived from limited germline gene families, and its diversity may rely on junctional diversity and somatic hypermutation.