HLA‐DQB1*03:01:01:21Q, a novel HLA‐DQB1 allele, detected in a Spanish volunteer bone marrow donor

Abstract

HLA‐DQB1*03:01:01:21Q differs from HLA‐DQB1*03:01:01:03 by a single‐nucleotide substitution (G → A) at position 1 of intron 3.

RNA and protein expression analysis of HLA‐DQB1*03:01:01:21Q allele: A null allele renamed as HLA‐DQB1*03:01:01:21N

“…As previously described, 10 HLA typing by NGS of the bone marrow donor AB‐RED‐008283, revealed the presence of a single‐nucleotide (G→A) substitution at position 1 of intron 3 (gDNA 4629) when compared with DQB1*03:01:01:03 allele. This initial typing of HLA‐DQB1 locus included a sequence of 3806 bp from intron 1 to exon 4, thus, in order to confirm these results, the sequence of the whole gene was obtained by NGS.…”

“…The new allele HLA‐DQB1*03:01:01:21Q was detected during routine typing for HLA class I (HLA‐A, ‐B, and ‐C) and class II (HLA‐DRB1 and ‐DQB1) by next‐generation sequencing (NGS) of a female volunteer bone marrow donor, AB‐RED‐008283, from the Spanish registry 10 . The complete HLA typing of the volunteer bone marrow donor was: A*03:01:01:05, 24:02:01; B*07:02:01:01, 14:02:01:01; C*07:02:01, 08:02:01:01; DRB1*01:02P, 11:02:01; DQB1*03:01:01:21Q, 05:01:01:01 .…”

“…HLA typing for HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 loci by NGS was performed as previously described 10 . Briefly, library preparation was performed by using commercial NGSgo‐AmpX kits (GenDx, Utrecht, The Netherlands), this method covers a region from intron 1 to exon 4 of DQB1 gene.…”

“…Here, we describe the expression analysis of the allele HLA‐DQB1*03:01:01:21Q in a bone marrow donor. This new allele shows a substitution at position 1 of intron 3 when compared with DQB1*03:01:01:03 allele 10 . Given the location of this substitution, it is possible that it might disrupt the initial splice site in the intron 3 and affect the expression of this allele.…”

Identification of two novel HLA‐DQB1 alleles by next‐generation sequencing DQB1*04:73N and DQB1*03:19:01:02Q

“…Comparing with the closest DQB1*03:19:01:01 , the new allele has an intron 3 splice donor site mutation which changes the sequence from GT to AT immediately next to the end of exon 3. The only other reported DQB1 allele that has the same mutation at the beginning of intron 3 is DQB1*03:01:01:21Q 5 . Because it has the potential to disrupt the intron 3 splicing, the expression of this allele is questionable.…”