SEQUENCE AND EXPRESSION OF A CANDIDATE FOR THE HUMAN SECRETOR BLOOD-GROUP ALPHA(1,2)FUCOSYLTRANSFERASE GENE (FUT2) - HOMOZYGOSITY FOR AN ENZYME-INACTIVATING NONSENSE MUTATION COMMONLY CORRELATES WITH THE NON-SECRETOR PHENOTYPE
SEQUENCE AND EXPRESSION OF A CANDIDATE FOR THE HUMAN SECRETOR BLOOD-GROUP ALPHA(1,2)FUCOSYLTRANSFERASE GENE (FUT2) - HOMOZYGOSITY FOR AN ENZYME-INACTIVATING NONSENSE MUTATION COMMONLY CORRELATES WITH THE NON-SECRETOR PHENOTYPE
复制标题
DOI：
10.1074/jbc.270.9.4640
复制
发表时间：
1995-03-03
影响因子：
4.8
通讯作者：
LOWE, JB
中科院分区：
文献类型：
--
作者：
KELLY, RJ;ROUQUIER, S;LOWE, JB
人类可溶性A、B、H和刘易斯B血型抗原的合成由分泌型（Se）（FUT 2）血型基因座决定。遗传、生物化学和分子分析表明，该位点对应于与遗传连锁的H血型α（1，2）岩藻糖基转移酶位点不同的α（1，2）岩藻糖基转移酶基因。所附论文（Rouquier，S.，Lowe，J，B.，凯利河，巴西-地J.，费尔蒂塔，亚利桑那州，Lennon，G. G.，和Giorgi，D.（1995）J.Biol.Chem.270，4632-4639）描述了与H基因座物理连接并交叉杂交的两个人DNA区段的分子克隆和作图。我们在这里提出了这两个新的DNA片段的分析。其中之一，称为Sec 1，是假基因，因为翻译移码和终止密码子中断潜在的开放阅读框，否则将与H α（1，2）岩藻糖基转移酶共享一级序列相似性。另一个DNA片段，称为Seca，预测一个332个氨基酸长的多肽，和一个更长的同种型，与人H血型α（1，2）岩藻糖基转移酶的COOH末端292个残基共享68%的序列同一性。Sec 2编码具有催化性质的α（1，2）岩藻糖基转移酶，该催化性质反映了分泌子基因座编码的α（1，2）岩藻糖基转移酶的催化性质。大约20%的随机选择的个体被发现在该基因座上的酶失活无义等位基因（Trp（143）--> ter）是明显纯合的，与大多数人群中非分泌型表型的频率相对应。此外，六个无关的非分泌型个体中的每一个也是该无效等位基因的表观纯合子。这些结果表明，Seca对应于人类分泌型血型基因座（FUT 2），并表明一个共同的无义等位基因的纯合性是负责在许多非分泌型个体的nonsecretor表型。
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 lo cus. 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 Seca, 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 (Trp(143) --> 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 apparentry homozygous for this null allele. These results indicate that Seca 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.