[Sequence Analysis and Confirmation of an HLA Null Allele Generated by a Base Insertion]

Area of Science:

• Human Leukocyte Antigen (HLA) genetics
• Molecular typing techniques
• Immunogenetics

Context:

• Accurate HLA typing is crucial for hematopoietic stem cell transplantation and understanding immune responses.
• Routine HLA detection methods like PCR sequence-specific oligonucleotide probe (SSOP) and PCR sequence-based typing (SBT) may encounter challenges with novel alleles.
• An abnormal HLA-C sequence was observed in a patient with acute myeloid leukemia.

Purpose:

• To confirm the sequence of the null allele *HLA-C*08:127N.
• To investigate the impact of a base insertion on HLA allele identification.
• To compare the efficacy of different HLA typing technologies.

Summary:

• PCR-SSOP and SBT initially suggested an abnormal *HLA-C* sequence in an acute myeloid leukemia patient.
• PCR-SBT indicated a potential insertion or deletion in exon 3.
• Next-generation sequencing (NGS) definitively identified the null allele as *HLA-C*08:127N, confirming a base insertion.

Impact:

• Next-generation sequencing (NGS) provides accurate HLA typing results, even with complex variations like base insertions.
• Standard SBT analysis software may yield incorrect results for null alleles caused by base insertions.
• This study highlights the importance of advanced sequencing technologies for precise HLA allele discovery and characterization.