Two Prevalent ∼100-kb GYPB Deletions Causative of the GPB-Deficient Blood Group MNS Phenotype S-s-U- in Black Africans
Two Prevalent ∼100-kb GYPB Deletions Causative of the GPB-Deficient Blood Group MNS Phenotype S-s-U- in Black Africans
复制标题
DOI：
10.1159/000504946
复制
发表时间：
2020-07-01
影响因子：
2.2
通讯作者：
Frey, Beat M.
中科院分区：
文献类型：
--
作者：
Gassner, Christoph;Denomme, Gregory A.;Frey, Beat M.
U抗原(MNS5)是血糖素A(GPA)和血糖素B(GPB)携带的MNS血型系统(ISBT002)的49种抗原之一。在几乎所有的欧洲人和亚洲人的红细胞上都存在U，但在大约1.0%的非洲黑人中没有。U负值与S和S在GPB上的负值一致，因此被称为S-S-U-，被认为是由GYPB纯合缺失引起的。人们对这些缺失的分子背景知之甚少。对1000基因组计划数据的生物信息学分析揭示了GYPB中几个明显缺失的候选区域。高度特异的缺口-聚合酶链式反应，只导致DNA的阳性扩增，存在缺失，允许对3个不同的断裂点进行准确的基因定位；110.24和103.26 kb的缺失被证明在美国黑人和非洲人中最常见。在157个CEPH DNA中，8个非洲种族中有6个存在缺失。非洲种族内缺失的等位基因频率差异很大，在刚果Mbuti俾格米人中累计达到23.3%。U+(Var)等位基因也有类似的观察结果，已知会导致GPB表达显著降低。110kb和103kb缺失的GYPB单倍型代表了导致MNS血型表型S-S-U-的最常见的遗传因素。GYPB缺失现在可以通过对同型和半合子遗传的分子检测来实现。
The U antigen (MNS5) is one of 49 antigens belonging to the MNS blood group system (ISBT002) carried on glycophorins A (GPA) and B (GPB). U is present on the red blood cells in almost all Europeans and Asians but absent in approximately 1.0% of Black Africans. U negativity coincides with negativity for S (MNS3) and s (MNS4) on GPB, thus be called S-s-U-, and is thought to arise from homozygous deletion ofGYPB. Little is known about the molecular background of these deletions. Bioinformatic analysis of the 1000 Genomes Project data revealed several candidate regions with apparent deletions inGYPB. Highly specific Gap-PCRs, only resulting in positive amplification from DNAs with deletions present, allowed for the exact genetic localization of 3 different breakpoints; 110.24- and 103.26-kb deletions were proven to be the most frequent in Black Americans and Africans. Among 157 CEPH DNAs, deletions in 6 out of 8 African ethnicities were present. Allele frequencies of the deletions within African ethnicities varied greatly and reached a cumulative 23.3% among the Mbuti Pygmy people from the Congo. Similar observations were made for U+(var) alleles, known to cause strongly reduced GPB expression. The 110- and 103-kb deletionalGYPBhaplotypes were found to represent the most prevalent hereditary factors causative of the MNS blood group phenotype S-s-U-. RespectiveGYPBdeletions are now accessible by molecular detection of homo- and hemizygous transmission.