Organization of the variable region of the immunoglobulin heavy-chain gene locus of the rat

Abstract

We have mapped and annotated the variable region of the immunoglobulin heavy (IGH) gene locus of the Brown Norway (BN) rat (assembly V3.4; Rat Genomic Sequence Consortium). In addition to known variable region genes, we found 12 novel previously unidentified functional IGHV genes and 1 novel functional IGHD gene. In total, the variable region of the rat IGH locus is composed of at least 353 unique IGHV genes, 21 IGHD genes, and 5 IGHJ genes, of which 131, 14, and 4 are potentially functional genes, respectively. Of all species studied so far, the rat seems to have the highest number of functional IGHV genes in the genome. Rat IGHV genes can be classified into 13 IGHV families based on nucleotide sequence identity. The variable region of the BN rat spans a total length of approximately 4.9 Mb and is organized in a typical translocon organization. Like the mouse, members of the various IGHV gene families are more or less grouped together on the genome, albeit some members of IGHV gene families are found intermingled with each other. In the rat, the largest IGHV gene families are IGHV1, IGHV2, and IGHV5. The overall conclusion is that the genomic organization of the variable region of the rat IGH locus is strikingly similar to that of the mouse, illustrating the close evolutionary relationship between these two species.

Fig. 1

Chromosomal map of the variable region of the IGH locus of the BN rat. Shown is the IGHV region from chromosome 6 ranging from gene Znf386 to IGHJ4 (RGSC V3.4: 138,451,833–143,326,393 bp). The map was established on the basis of the IMGT database (http://imgt.cines.fr), as indicated in “Materials and Methods,” and does not contain the 12 newly identified IGHV genes. Genes and their orientation are indicated by an arrow point. The IGHV, IGHD, and IGHJ genes are numbered according to the IMGT nomenclature (Lefranc et al. 1999). Members of the same IGHV family share identical colors (non-IGHV genes are shown in gray). Nonfunctional genes are indicated with a “p” for pseudogene or with an “r” for ORF gene after the family number. The last number in the gene name is the rank number of the gene in the locus, starting at the centromeric end. Black dotted lines indicate near-perfect inverted repeats. Gaps in assembly V3.4 are marked by solid gray bars. This map is also available as an MS Excel file (Online Resource 1) and as a “bed”-type file (Online Resource 2) that can be projected on the current rat genome version V3.4 at the UCSC genome website (www.genome.ucsc.edu). These files can be found in “Supplementary Material”