Four Non-functional FUT1 Alleles Were Identified in Seven Chinese Individuals with Para-Bombay Phenotypes
Background: The para-Bombay phenotype is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for seven Chinese individuals serologically typed as para-Bombay in Blood Station Center of Ningbo, Zhejiang Province, Ningbo, China from 2011 to 2014.
Methods: RBCs’ phenotype was characterized by standard serologic technique. Genomic DNA was sequenced with primers that amplified the coding sequence of α (1, 2)-fucosyltransferase genes FUT1 (or H) and FUT2 (or Se), respectively. Routine ABO genotyping analysis was performed. Haplotypes of FUT1 were identified by TOPO cloning sequencing. Phylogenetic tree of H proteins of different organisms was performed using Mega 6 software.
Results: Seven independent individuals were demonstrated to possess the para-Bombay phenotype. RBC ABO genotypes correlated with ABH substances in their saliva. FUT1 547delAG (h1), FUT1 880delTT (h2), FUT1 658T (h3) and FUT1 896C were identified in this study. FUT1 896C was first revealed by our team. The H-deficient allele reported here was rare and the molecular basis for H deficient alleles was diverse as well in the Chinese population. In addition, the FUT2 was also analyzed, only one FUT2 allele was detected in our study: Se357. Phylogenetic tree of the H proteins showed that H proteins could work as an evolutionary and genetic marker to differentiate organisms in the world.
Conclusion: Molecular genetic backgrounds of seven Chinese individuals were summarized sporadic and random mutations in the FUT1 gene are responsible for the inactivation of the FUT1-encoded enzyme activity.
Zhang A, Chi Q, Ren B (2015). Genomic analysis of para- Bombay individuals in south-eastern China: the possibility of linkage and disequilibrium between FUT1 and FUT2. Blood Transfus, 13(3): 472-477.
Ball SP, Tongue N, Gibaud A et al (1991). The human chromosome 19 linkage group FUT1 (H), FUT2 (SE), LE, LU, PEPD, C3, APOC2, D19S7 and D19S9. Ann Hum Genet, 55(Pt 3): 225-233.
Reguigne-Arnould I, Couillin P, Mollicone R et al (1995). Relative positions of two clusters of human alpha-L-fucosyltransferases in 19q (FUT1-FUT2) and 19p (FUT6-FUT3-FUT5) within the microsatellite genetic map of chromo-some 19. Cytogenet Cell Genet, 71(2): 158-162.
Oriol R, Danilovs J, Hawkins BR (1981). A new genetic model proposing that the Se gene is a structural gene closely linked to the H gene. Am J Hum Genet, 33(3): 421-431.
Le Pendu J, Cartron JP, Lemieux RU, et al (1985). The presence of at least two dif-ferent H-blood-group-related beta-D-gal alpha-2-L-fucosyltrans- ferases in human serum and the genetics of blood group H substances. Am J Hum Genet, 37(4): 749-760.
Matsushita M, Otani K, Sakamoto Y, et al (2015). Increase in Alkaline Phosphatase Activity after High-Fat Meal Ingestion is Correlated to the Amount of ABH Sub-stances in Saliva. Rinsho Byori, 63(5): 543-547.
Yip SP, Chee KY, Chan PY, et al (2002). Molecular genetic analysis of para-Bombay phenotypes in Chinese: a novel non-functional FUT1 allele is identified. Vox Sang, 83(3): 258-262.
Saitou N, Nei M (1987). The neighbor-joining method: a new method for re-constructing phylogenetic trees. Mol Biol Evol, 4(4): 406-425.
Zuckerkandl E, Pauling L (1965). Evolution-ary divergence and convergence in pro-teins. Edited in Evolving Genes and Pro-teins by Bryson V and Vogel HJ, Aca-demic Press. New York, 97-166.
Tamura K, Stecher G, Peterson D, et al (2013). MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol, 30(12): 2725-9.
Yu LC, Yang YH, Broadberry RE, et al (1997). Heterogeneity of the human H blood group alpha(1,2)fucosyltransferase gene among para-Bombay individuals. Vox Sang, 72(1): 36-40.
Liang W, Xu H, Liu YY, et al (2015). Molec-ular genetic analysis of para-Bombay phenotype in Chinese persons: a novel FUT1 allele is identified. Transfusion, 55(6 Pt 2): 1588.
Blumenfeld OO, Patnaik SK (2004). Allelic genes of blood group antigens: a source of human mutations and cSNPs docu-mented in the Blood Group Antigen Gene Mutation Database. Hum Mutat, 23(1): 8-16.
Cai XH, Jin S, Liu X, et al (2011). Molecular genetic analysis for the para-Bombay blood group revealing two novel alleles in the FUT1 gene. Blood Transfus, 9(4): 466-468.
Wang B, Koda Y, Soejima M, et al (1997). Two missense mutations of H type al-pha(1,2)fucosyltransferase gene (FUT1) responsible for para-Bombay phenotype. Vox Sang, 72(1): 31-35.
Xu X, Tao S, Ying Y, et al (2011). A novel FUT1 allele was identified in a Chinese individual with para-Bombay phenotype. Transfus Med, 21(6): 385-393.
Kelly RJ, Rouquier S, Giorgi D, et al (1995). Sequence and expression of a candidate for the human Secretor blood group al-pha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem, 270(9): 4640-9.
Storry JR, Johannesson JS, Poole J, et al (2006). Identification of six new alleles at the FUT1 and FUT2 loci in ethnically di-verse individuals with Bombay and Para-Bombay phenotypes. Transfusion, 46(12): 2149-2155.
Ali S, Niang MA, N'doye I, et al (2000). Se-cretor polymorphism and human immu-nodeficiency virus infection in Senegalese women. J Infect Dis, 181(2): 737-739.
Thorven M, Grahn A, Hedlund KO, et al (2005). A homozygous nonsense muta-tion (428G-->A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infec-tions. J Virol, 79(24): 15351-5.
Kindberg E, Hejdeman B, Bratt G, et al (2006). A nonsense mutation (428G-->A) in the fucosyltransferase FUT2 gene af-fects the progression of HIV-1 infection. AIDS, 20(5): 685-9.
Wagner FF, Flegel WA (1997). Polymor-phism of the h allele and the population frequency of sporadic nonfunctional al-leles. Transfusion, 37(3): 284-290.
Kaneko M, Nishihara S, Shinya N, et al (1997). Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme. Blood, 90(2): 839-849.
Bhende YM, Deshpande CK, Bhatia HM, et al (1994). A "new" blood-group character related to the ABO system. 1952. Indian J Med Res, 99: 3p.
Koda Y, Soejima M, Johnson PH, et al (1997). Missense mutation of FUT1 and deletion of FUT2 are responsible for In-dian Bombay phenotype of ABO blood group system. Biochem Biophys Res Commun, 238(1): 21-25.
Yan L, Zhu F, Xu X, et al (2005). Molecular basis for para-Bombay phenotypes in Chinese persons, including a novel non-functional FUT1 allele. Transfusion, 45(5): 725-730.
Liu Y, Koda Y, Soejima M, et al (1998). Ex-tensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa. Hum Genet, 103(2): 204-210.
Henry S, Mollicone R, Fernandez P, et al (1996). Molecular basis for erythrocyte Le(a+ b+) and salivary ABH partial-secretor phenotypes: expression of a FUT2 secretor allele with an A-->T muta-tion at nucleotide 385 correlates with re-duced alpha(1,2) fucosyltransferase activi-ty. Glycoconj J, 13(6): 985-993.
Kudo T, Iwasaki H, Nishihara S, et al (1996). Molecular genetic analysis of the human Lewis histo-blood group system. II. Se-cretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals. J Biol Chem, 271(16): 9830-7.
Koda Y, Ishida T, Tachida H, et al (2003). DNA sequence variation of the human ABO-secretor locus (FUT2) in New Guinean populations: possible early hu-man migration from Africa. Hum Genet, 113(6): 534-541.
|Issue||Vol 47 No 8 (2018)|
|FUT1 FUT2 Para-Bombay phenotype|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|