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Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers.使用下一代测序仪对经典HLA基因座进行8位水平的单分子序列分型的超高分辨率。
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[Allelic and haplotypic diversity of HLA-A, -B, -C, and -DRB1 genes in Koreans defined by high-resolution DNA typing].[通过高分辨率DNA分型确定的韩国人HLA - A、- B、- C和 - DRB1基因的等位基因和单倍型多样性]
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通过多组特异性序列分型法解决韩国人群中HLA基因分型不明确的问题。

Resolution of ambiguous HLA genotyping in korean by multi-group-specific sequence-based typing.

作者信息

Park Yongjung, Yoon Cha Eun, Kwon Oh-Joong, Kim Yu-Seun, Kim Hyon-Suk

机构信息

Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Biowithus Life Science Institute, Seoul, Korea.

出版信息

Yonsei Med J. 2014 Jul;55(4):1005-13. doi: 10.3349/ymj.2014.55.4.1005.

DOI:10.3349/ymj.2014.55.4.1005
PMID:24954331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4075361/
Abstract

PURPOSE

To evaluate a multi-group-specific sequence-based typing (SBT) method for resolving ambiguous results from human leukocyte antigen (HLA) genotyping.

MATERIALS AND METHODS

A total of 50 samples that showed ambiguous genotypes for at least two HLA loci from HLA-A, -B, -C and -DRB1 by the conventional SBT assay were evaluated using a new SBT test, the AVITA plus assay. The most likely HLA genotypes for the respective samples considering allele frequencies in Korean were concordant between the AVITA and conventional SBT assays.

RESULTS

An average of 3.3 loci among the HLA-A, -B, -C and -DRB1 loci per sample gave results with two or more possible allele combinations with the conventional SBT, and 48 (96.0%) out of 50 showed reduced numbers of possible genotypes for at least one HLA locus with the AVITA. A total of 41, 43, 42, and 38 cases among the 50 samples showed ambiguous results for HLA-A, -B, -C, and -DRB1 typing by the conventional SBT, respectively. The average numbers of possible allele combinations for the respective four HLA loci were 8.2, 6.7, 5.9, and 3.2, and they were reduced to 1.5, 2.2, 4.4, and 1.8, respectively, by the AVITA. Ambiguity was resolved by the AVITA in 33 (80.5%), 31 (72.1%), 17 (40.5%) and 28 (73.7%) samples among the ambiguous cases from the conventional SBT for HLA-A, -B, -C, and -DRB1 typing, respectively.

CONCLUSION

The multi-group-specific SBT method considerably reduced the number of ambiguous results, and thus may be useful for accurate HLA typing in clinical laboratories.

摘要

目的

评估一种基于多组特异性序列的分型（SBT）方法，以解决人类白细胞抗原（HLA）基因分型中出现的模糊结果。

材料与方法

使用一种新的SBT检测方法——AVITA plus检测法，对50份通过传统SBT检测在HLA-A、-B、-C和-DRB1中至少两个HLA位点显示模糊基因型的样本进行评估。考虑到韩国人群中的等位基因频率，AVITA检测法和传统SBT检测法对各个样本最可能的HLA基因型结果一致。

结果

每个样本的HLA-A、-B、-C和-DRB1位点中，平均有3.3个位点通过传统SBT检测得到两种或更多种可能的等位基因组合结果，50份样本中有48份（96.0%）至少在一个HLA位点上通过AVITA检测法显示可能的基因型数量减少。在50份样本中，分别有41、43、42和38例通过传统SBT检测在HLA-A、-B、-C和-DRB1分型中显示模糊结果。四个HLA位点各自可能的等位基因组合平均数分别为8.2、6.7、5.9和3.2，通过AVITA检测法分别降至1.5、2.2、4.4和1.8。在传统SBT检测HLA-A、-B、-C和-DRB1分型的模糊病例中，AVITA检测法分别在33份（80.5%）、31份（72.1%）、17份（40.5%）和28份（73.7%）样本中解决了模糊性。

结论

多组特异性SBT方法显著减少了模糊结果的数量，因此可能有助于临床实验室进行准确的HLA分型。