MOLECULAR-BASIS FOR H-BLOOD-GROUP DEFICIENCY IN BOMBAY (O-H) AND PARA-BOMBAY INDIVIDUALS
MOLECULAR-BASIS FOR H-BLOOD-GROUP DEFICIENCY IN BOMBAY (O-H) AND PARA-BOMBAY INDIVIDUALS
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DOI：
10.1073/pnas.91.13.5843
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发表时间：
1994-06-21
影响因子：
11.1
通讯作者：
LOWE, JB
中科院分区：
文献类型：
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作者：
KELLY, RJ;ERNST, LK;LOWE, JB
人ABO血型寡糖抗原生物合成的倒数第二步由α-（1，2）岩藻糖基转移酶（GDP-L-岩藻糖：β-D-半乳糖苷2-α-L-岩藻糖基转移酶，EC 2.4.1.69）催化，其表达由H和分泌（SE）血型基因座（也分别称为FUT 1和FUT 2）决定。这些酶构建Fuc α 1 -> 2Gal β-连接，称为H决定簇，其是A和B抗原的必需前体。来自具有罕见孟买和类孟买血型表型的个体的红细胞缺乏H决定簇，因此缺乏A和B决定簇，这是H基因座上无效等位基因表观纯合性的结果。我们报告的人α-（1，2）-岩藻糖基转移酶基因的分子分析，被认为是对应于H血型位点，在孟买血统和准孟买血统。我们发现失活点突变的编码区的两个等位基因的这个基因在每个H-缺陷的个人，这些结果定义的H血型抗原缺乏症在孟买和para-Bombay表型的分子基础，提供令人信服的证据表明，这个基因代表人类H血型基因座，并强烈支持一个假设，即H和SE基因座代表不同的α-（1，2）-岩藻糖基转移酶基因。人SE基因座的候选序列通过低严格性Southern印迹杂交分析鉴定，使用源自H α-（1，2）-岩藻糖基转移酶基因的探针。
The penultimate step in the biosynthesis of the human ABO blood group oligosaccharide antigens is catalyzed by alpha-(1,2)fucosyltransferase(s) (GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase, EC 2.4.1.69), whose expression is determined by the H and Secretor (SE) blood group loci (also known as FUT1 and FUT2, respectively). These enzymes construct Fuc alpha 1 --> 2Gal beta-linkages, known as H determinants, which are essential precursors to the A and B antigens. Erythrocytes from individuals with the rare Bombay and para-Bombay blood group phenotypes are deficient in H determinants, and thus A and B determinants, as a consequence of apparent homozygosity for null alleles at the H locus. We report a molecular analysis of a human alpha-(1,2)-fucosyltransferase gene, thought to correspond to the H blood group locus, in a Bombay pedigree and a para-Bombay pedigree. We find inactivating point mutations in the coding regions of both alleles of this gene in each H-deficient individual, These results define the molecular basis for H blood group antigen deficiency in Bombay and para-Bombay phenotypes, provide compelling evidence that this gene represents the human H blood group locus, and strongly support a hypothesis that the H and SE loci represent distinct alpha-(1,2) -fucosyltransferase genes. Candidate sequences for the human SE locus are identified by low-stringency Southern blot hybridization analyses, using a probe derived from the H alpha-(1,2)-fucosyltransferase gene.