Patterns of non-ARD variation in more than 300 full-length HLA-DPB1 alleles.

Patterns of non-ARD variation in more than 300 full-length HLA-DPB1 alleles. Hum Immunol. 2018 Jun 04;: Authors: Klasberg S, Lang K, Günther M, Schober G, Massalski C, Schmidt AH, Lange V, Schöfl G Abstract Our understanding of sequence variation in the HLA-DPB1 gene is largely restricted to the hypervariable antigen recognition domain (ARD) encoded by exon 2. Here, we employed a redundant sequencing strategy combining long-read and short-read data to accurately phase and characterise in full length the majority of common and well-documented (CWD) DPB1 alleles as well as alleles with an observed frequency of at least 0.0006% in our predominantly European sample set. We generated 664 DPB1 sequences, comprising 279 distinct allelic variants. This allows us to present the, to date, most comprehensive analysis of the nature and extent of DPB1 sequence variation. The full-length sequence analysis revealed the existence of two highly diverged allele clades. These clades correlate with the rs9277534 A→G variant, a known expression marker located in the 3'-UTR. The two clades are fully differentiated by 174 fixed polymorphisms throughout a 3.6 kB stretch at the 3'-end of DPB1. The region upstream of this differentiation zone is characterised by increasingly shared variation between the clades. The low-expression A clade comprises 59% of the distinct allelic sequences including the three by far most frequent DPB1 alleles, DPB1*04:01, DPB1...
Source: Human Immunology - Category: Allergy & Immunology Authors: Tags: Hum Immunol Source Type: research