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题名: Genomic Typing of Human Red Cell Miltenberger Glycophorins in a Taiwanese Population
作者: Shih, M. C.;Yang, L. H.;Wang, Nancy M.;Chang, J. G.
贡献者: 生物技術研究所
日期: 2000-01
上传时间: 2012-06-06T02:03:59Z
出版者: John Wiley & Sons, Inc.
摘要: BACKGROUND: Antigens in the human red cell Miltenberger series are glycophorin variants of the MN (MNS) blood group system that are due to the rearrangement of glycophorin A (GPA) and glycophorin B (GPB) genes.

STUDY DESIGN AND METHODS: Taking advantage of the differences between the GPA and GPB genes, a polymerase chain reaction-based method was developed to detect all the Miltenberger glycophorin variants and Sta subtype. GPA- and GPB-specific primers were used to amplify the GPA or GPB gene, and the amplified products were used to recognize the different hybrid genes after restriction enzyme digestions.

RESULTS: Among 264 Taiwanese subjects studied, Mi.III and Sta are the most common types of Miltenberger variants found. Mi.III was present in 13 (4.92%) of 264, and Sta was found in 8 (3.03%) of 264; 1 case (0.4%) of Mi.V was also identified from the study group.

CONCLUSION: This is the first polymerase chain reaction-based method of detecting most of the Miltenberger variants and Sta. The genomic typing results were confirmed by control DNA of identified Miltenberger phenotypes. The prevalence rates of Mi.III and Sta in this study were also consistent with other previous reports using different methods.

Human glycophorins are the major sialoglyco-proteins expressed on the red cell membrane that carry the antigens of the MN (MNS) blood group system.1 They are encoded by a gene family that includes at least three common members: glycophorin A (GPA), glycophorin B (GPB), and glycophorin E (GPE). These genes are present as a single copy in the haploid genome, and they share extensive sequence homology in both coding and noncoding regions, except for the extracellular and cytoplasmic domains. The GPA (α) gene contains seven actively expressed exons, while the GPB (δ) and GPE (ɛ) genes lack exons for the cytoplasmic domains. The third exon of GPB and the third and fourth exons of GPE are silent pseudo-exons because of the inactivation of their donor-splice sites by point mutations at the first position of GT dinucleotides.2–4

Studies of genetic variation in the glycophorin genes have shown that variant genes frequently are hybrids from parts of the parental genes arranged in various configurations.4 This suggests that antigenic variation in the human MN (MNS) blood group system occurs predominantly through DNA recombination. The hybrids can be assembled in four basic configurations with respect to the arrangement of parent genes. They are GPA-B, GPB-A, GPA-B-A, and GPB-A-B, which are the results of nucleotide (nt) sequence homology and special DNA motifs inherent from the parent genes. Analysis of all the recombinations shows that all the events occur at the MN (MNS) locus within a genomic region of approximately 4 kb that spans exons of the parent genes encoding the extracellular domain. Moreover, in 18 of 20 variants, genetic exchanges are confined to a 2-kb region spanning from exon II through exon IV.5

Antigens in the Miltenberger series are variants of the MN (MNS) blood group system. As a subsystem of the MN blood group, the antigens in the Miltenberger series all occur through gene rearrangements during the recombination of the parental genes.5,6 These variants were determined by using serologic and biochemical methods in the past,7–10 and some genetics methods have been used for their detection.11–16 In this study, we developed a comprehensive polymerase chain reaction (PCR)-based method of detecting most of the Miltenberger variants, and then we used this new technique to screen for Miltenberger variants among a Taiwanese population to understand the prevalence of these variants in that group.
關聯: Transfusion, 40(1): 54-61
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