Characterization of a rare HLA-C*08:84 allele and analysis of its 3-D molecular structure / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure.@*METHODS@#PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software.@*RESULTS@#Analysis indicated that the rare allele (HLA-C*0884) has transmitted from the proband's mother and has differed from HLA-C*0801 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*0884, C*0801, C*0802, C*0803 and C*0822 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively.@*CONCLUSION@#A rare HLA-C*0884 allele has been identified, and its clinical significance has been analyzed.