MOLECULAR-BASIS FOR H-BLOOD-GROUP DEFICIENCY IN BOMBAY (O-H) AND PARA-BOMBAY INDIVIDUALS

被引:150
作者
KELLY, RJ
ERNST, LK
LARSEN, RD
BRYANT, JG
ROBINSON, JS
LOWE, JB
机构
[1] UNIV MICHIGAN, HOWARD HUGHES MED INST, ANN ARBOR, MI 48109 USA
[2] UNIV MICHIGAN, DEPT PATHOL, ANN ARBOR, MI 48109 USA
[3] AMER RED CROSS, REFERENCE LAB, CHARLOTTE, NC 28203 USA
[4] UNIV KENTUCKY, MED CTR, BLOOD BANK, LEXINGTON, KY 40536 USA
关键词
ABO BLOOD GROUP; SECRETOR BLOOD GROUP; OLIGOSACCHARIDE BIOSYNTHESIS; FUCOSYL-TRANSFERASE; SURFACE ANTIGEN;
D O I
10.1073/pnas.91.13.5843
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:5843 / 5847
页数:5
相关论文
共 25 条
[1]  
AUSUBEL J, 1987, MOL BIOL LABORATORY, V2
[2]  
AUSUBEL J, 1987, MOL BIOL LABORATORY, V1
[3]   INCIDENCE OF BOMBAY (OH) PHENOTYPE AND WEAKER VARIANTS OF A AND B ANTIGEN IN BOMBAY (INDIA) [J].
BHATIA, HM ;
SATHE, MS .
VOX SANGUINIS, 1974, 27 (06) :524-532
[4]  
BHENDE YM, 1952, LANCET, V262, P903
[5]   BIOSYNTHETIC PATHWAYS FOR THE LEB-GLYCOLIPIDS AND Y-GLYCOLIPIDS IN THE GASTRIC-CARCINOMA CELL-LINE KATO III AS ANALYZED BY A NOVEL ASSAY [J].
BLASZCZYKTHURIN, M ;
SARNESTO, A ;
THURIN, J ;
HINDSGAUL, O ;
KOPROWSKI, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 151 (01) :100-108
[6]  
BRYANT JG, 1974, TRANSFUSION, V14, P506
[7]   RNA EDITING - EXPLORING ONE MODE WITH APOLIPOPROTEIN-B MESSENGER-RNA [J].
CHAN, L .
BIOESSAYS, 1993, 15 (01) :33-41
[8]   DNA TYPING FROM SINGLE HAIRS [J].
HIGUCHI, R ;
VONBEROLDINGEN, CH ;
SENSABAUGH, GF ;
ERLICH, HA .
NATURE, 1988, 332 (6164) :543-546
[9]   DETERMINANTS OF CA2+ PERMEABILITY IN BOTH TM1 AND TM2 OF HIGH-AFFINITY KAINATE RECEPTOR CHANNELS - DIVERSITY BY RNA EDITING [J].
KOHLER, M ;
BURNASHEV, N ;
SAKMANN, B ;
SEEBURG, PH .
NEURON, 1993, 10 (03) :491-500
[10]   ALTERING GENES IN ANIMALS BY GENE TARGETING [J].
KOLLER, BH ;
SMITHIES, O .
ANNUAL REVIEW OF IMMUNOLOGY, 1992, 10 :705-730