Kelly R J, Rouquier S, Giorgi D, Lennon G G, Lowe J B
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650.
J Biol Chem. 1995 Mar 3;270(9):4640-9. doi: 10.1074/jbc.270.9.4640.
Synthesis of soluble A, B, H, and Lewis b blood group antigens in humans is determined by the Secretor (Se) (FUT2) blood group locus. Genetic, biochemical, and molecular analyses indicate that this locus corresponds to an alpha(1,2)fucosyltransferase gene distinct from the genetically-linked H blood group alpha(1,2)fucosyltransferase locus. The accompanying paper (Rouquier, S., Lowe, J. B., Kelly, R. J., Fertitta, A. L., Lennon, G. G., and Giorgi, D. (1995) J. Biol. Chem. 270, 4632-4639) describes the molecular cloning and mapping of two human DNA segments that are physically linked to, and cross-hybridize with, the H locus. We present here an analysis of these two new DNA segments. One of these, termed Sec1, is a pseudogene, because translational frameshifts and termination codons interrupt potential open reading frames that would otherwise share primary sequence similarity with the H alpha(1,2)fucosyltransferase. The other DNA segment, termed Sec2, predicts a 332-amino acid-long polypeptide, and a longer isoform, that share 68% sequence identity with the COOH-terminal 292 residues of the human H blood group alpha(1,2)fucosyltransferase. Sec2 encodes an alpha(1,2)fucosyltransferase with catalytic properties that mirror those ascribed to the Secretor locus-encoded alpha(1,2)fucosyltransferase. Approximately 20% of randomly-selected individuals were found to be apparently homozygous for an enzyme-inactivating nonsense allele (Trp143-->ter) at this locus, in correspondence to the frequency of the non-secretor phenotype in most human populations. Furthermore, each of six unrelated non-secretor individuals are also apparently homozygous for this null allele. These results indicate that Sec2 corresponds to the human Secretor blood group locus (FUT2) and indicate that homozygosity for a common nonsense allele is responsible for the nonsecretor phenotype in many non-secretor individuals.
人类中可溶性A、B、H和Lewis b血型抗原的合成由分泌型（Se）（FUT2）血型位点决定。遗传学、生物化学和分子分析表明，该位点对应于一个α（1,2）岩藻糖基转移酶基因，它不同于与H血型α（1,2）岩藻糖基转移酶位点遗传连锁的基因。随附论文（鲁基耶，S.，洛，J. B.，凯利，R. J.，费尔蒂塔，A. L.，列侬，G. G.，和乔吉，D.（1995年）《生物化学杂志》270，4632 - 4639）描述了与H位点物理连锁并与之交叉杂交的两个人类DNA片段的分子克隆和定位。我们在此展示对这两个新DNA片段的分析。其中一个称为Sec1，是一个假基因，因为翻译移码和终止密码子打断了潜在的开放阅读框，否则这些开放阅读框会与Hα（1,2）岩藻糖基转移酶具有一级序列相似性。另一个DNA片段称为Sec2，预测有一个332个氨基酸长的多肽以及一个更长的异构体，它们与人类H血型α（1,2）岩藻糖基转移酶的COOH末端292个残基具有68%的序列同一性。Sec2编码一种α（1,2）岩藻糖基转移酶，其催化特性与归因于分泌型位点编码的α（1,2）岩藻糖基转移酶的特性相似。在随机选择的个体中，约20%在该位点对于一个使酶失活的无义等位基因（Trp143→ter）明显是纯合的，这与大多数人类群体中非分泌型表型的频率一致。此外，六个不相关的非分泌型个体中的每一个在这个无效等位基因上也明显是纯合的。这些结果表明Sec2对应于人类分泌型血型位点（FUT2），并表明许多非分泌型个体中常见无义等位基因的纯合性导致了非分泌型表型。
