We have previously reported a couple of new putative D alleles. An IGHD3-10 allele was inferred from Sanger sequencing data (Lee CE et al 2006. Immunogenetics 57: 917-25), and an IGHD3-16 allele was reported from 454 data in Boyd et al 2010 (J Immunol; 184: 6986-92). These sequences are:
I think D alleles should be on our radar, and I agree that by restricting analysis to relatively unmutated V genes it should be pretty straight forward to pick up allelic variants. I think it is also true that if an unknown D gene is too different from those we know, it could slip through unseen in our analyses. I was interested to find solutions to D-less alignments for many years, and never saw anything that suggested there were other genes, but my datasets were tiny by today’s standards.
One explanation for ‘D-less" VDJs is that many D genes are too short to detect, and a simple analysis of 5’ and 3’ removals from D genes shows that there must be many D genes that are below the minimum length required to make a positive call. I agree though that I have never been sure that this can explain all the sequences for which we can’t identify a D gene.
Since we are talking D genes, the 2006 paper mentioned above (Lee CE et al 2006) suggests that the IMGT classification of D genes may not be correct . We concluded that IGHD4-23 and IGHD5-24 are functional, but IMGT reports them as open reading frames of uncertain functionality. IGHD1-14*01 and IGHD6-25 are defined as functional by IMGT, but we concluded this was not true.
I would be interested to know if we can reach agreement on this today.