Only d_fl16, d_sp2, and d_q52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which d_fl16 and d_sp2 originate from the same primordial d_h gene

Abstract

In mice, 12 germ-line DH genes belonging to three different families (DQ52, DSP2 and DFL16) have been identified. The DH genes other than DQ52 are clustered in the 60 kb-long region located between VH and JH genes. Since there are seven DH gene families (DHQ52, DXP, DA, DK, DN, DM and DLR) in humans, we tried to identify new DH gene families in the 60 kb-long region using human DH gene probes. Mouse and human DH genes showing the highest similarity were mouse DFL16 genes and human DA genes. Southern hybridization of the mouse clones covering the 60-kb region with human DH probes did not detect any other DH genes. Nucleotide sequence analysis of the 4.0-kb fragment containing the DFL16.1 gene confirmed this conclusion. Comparison of the 12 germ-line DH genes and more than 150 somatic DH sequences also indicated that there are not more germ-line DH genes in the mouse genome. Moreover, comparison of nucleotide sequences of DFL16.1 and DSP2.2 genes and their surrounding regions suggests that both DH gene families originate from the same primordial DH gene. Using the flanking sequences of both DH genes, the divergence date between DFL16 and DSP2 genes was estimated at around 37 million years ago.

Sequence and Characterization of the Ig Heavy Chain Constant and Partial Variable Region of the Mouse Strain 129S1

“…Although D H gene usage and the role of the D H region within the process of VDJ rearrangement have been intensively studied (29 -33), a complete nucleotide sequence of the D H region of BALB/c has never been published. The existing map is based on Southern blot hybridization experiments (34,35). The Mouse Genome Sequencing Consortium provided a complete sequence of the D H region of C57BL/6, which has recently been annotated (7,36).…”

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

“…DNA fragments amplified from 27 Dn/H-rearranged alleles were cloned and sequenced. The type of /H and DH segments used as well as the DH reading frame (RF; conventionally stan dardized relative to /H) were determined as described (Ichihara et al 1989;Chang et al 1992). Template-independent nucleotides (N), which are inserted by terminal deoxynucleotidyl transferase (Alt and Baltimore 1982;Desiderio et al 1984), and short pal indromic sequences (P), which are comple mentary to the ends of the recombining gene segments (Lafaille et al 1989), are listed.…”

Genetic Dissection of Lupus Pathogenesis: Sle3/5 Impacts IgH CDR3 Sequences, Somatic Mutations, and Receptor Editing

“…The obtained cell lysates were directly subjected to seminested PCR for detection of circular V H D gene excision products. The first round was done using P5 (conserved 3Ј of V H J558 family: 5Ј-TGAGGAGGAGGTAATAAATGGACA-3Ј) and P71 (conserved 5Ј of DFL16.1/DSP2.2: 5Ј-TCAAAGCACAATGCCTGGCTTGGG-3Ј) primers (21,22). The second round was performed using P6 (conserved 3Ј of V H J558 and more proximal to the coding sequence than P5: 5Ј-TC CCAGTGCAGCTTCCTGCTCCT-3Ј) and P71 primers (21).…”