在日本献血者中发现新型杂交基因和 St 抗原编码剪接位点突变。

Novel hybrid genes and a splice site mutation encoding the St antigen among Japanese blood donors.

机构信息

Kanto-Koshinetsu Block Blood Center, Japanese Red Cross Society, Tokyo, Japan.

Central blood institute, Japanese Red Cross Society, Tokyo, Japan.

出版信息

Vox Sang. 2020 Nov;115(8):756-766. doi: 10.1111/vox.12921. Epub 2020 May 11.

DOI:10.1111/vox.12921

PMID:32394466

Abstract

BACKGROUND

The low-incidence antigen St of the MNS system is usually associated with the GP(B-A) hybrid molecule, which carries the 'N' antigen at the N terminus. The GP(A-A) molecule with trypsin-resistant M antigen has been found in a few St(a+) individuals.

MATERIALS AND METHODS

Among Japanese blood donors, we screened 24 292 individuals for the presence of St(a+) with trypsin-resistant 'N' antigen and 193 009 individuals for the presence of St(a+) with trypsin-resistant M antigen. The breakpoints responsible for the St antigen were analysed by sequencing the genomic DNAs.

RESULTS

A total of 1001 (4·1%) individuals were identified as St(a+) with trypsin-resistant 'N' antigen. Out of 1001 individuals, 115 were selected randomly for sequencing. Two novel GYPSch (GYP401) variants with new intron 3 breakpoints of GYPA were detected in three cases. Twenty-five (0·013%) individuals were identified as St(a+) with trypsin-resistant M antigen. Five individuals had the GYP(A-ψB-A) hybrid allele; two of these five individuals were GYPZan (GYP101.01), and the remaining three had a novel GYP(A-ψB-A) allele with the first breakpoint in GYPA exon A3 between c.178 and c.203. Nine individuals had a novel GYP(A-E-A) allele with GYPE exon E2 and pseudoexon E3 instead of GYPA exon A2 and A3. The 11 remaining individuals had a novel GYP(A-A) allele with a 9-bp deletion that included the donor splice site of intron 3 of GYPA.

CONCLUSION

Our finding on diversity of glycophorin genes responsible for St antigen provides evidence for further complexity in the MNS system.

摘要

背景

MNS 系统的低频率抗原 St 通常与携带 N 末端“N”抗原的 GP(B-A) 杂交分子相关。在少数 St(a+)个体中发现了具有胰蛋白酶抗性 M 抗原的 GP(A-A)分子。

材料和方法

在日本献血者中，我们筛选了 24292 名个体，以确定是否存在具有胰蛋白酶抗性“N”抗原的 St(a+)，并筛选了 193009 名个体，以确定是否存在具有胰蛋白酶抗性 M 抗原的 St(a+)。通过测序基因组 DNA 分析导致 St 抗原的断点。

结果

共有 1001 名（4.1%）个体被鉴定为具有胰蛋白酶抗性“N”抗原的 St(a+)。在 1001 名个体中，随机选择了 115 名进行测序。在三个病例中发现了两种新的 GYPSch（GYP401）变体，它们具有 GYPA 新的内含子 3 断点。有 25 名（0.013%）个体被鉴定为具有胰蛋白酶抗性 M 抗原的 St(a+)。五名个体具有 GYP(A-ψB-A)杂交等位基因；其中两名个体具有 GYPZan（GYP101.01），其余三名个体具有新型 GYP(A-ψB-A)等位基因，第一个断点位于 GYPA 外显子 A3 的 c.178 和 c.203 之间。九名个体具有新型 GYP(A-E-A)等位基因，其 GYPE 外显子 E2 和假外显子 E3 代替了 GYPA 外显子 A2 和 A3。其余 11 名个体具有 GYP(A-A)等位基因，该基因缺失了 9 个碱基对，包括 GYPA 内含子 3 的供体位点。