Yuh-Ching Twu

Molecular genetic analysis for the Ae1 and A3 alleles.

BACKGROUND: In addition to the common ABO phenotypes, numerous phenotypes with a weak expression of the A or B antigens on RBCs have been found. This study describes the molecular genetic analysis of the Ael and the A3 phenotypes.

Phosphorylation status of transcription factor C/EBPα determines cell-surface poly-LacNAc branching (I antigen) formation in erythropoiesis and granulopoiesis

The cell-surface straight and branched repeats of N-acetyllactosamine (LacNAc) units, called poly-LacNAc chains, characterize the histo-blood group i and I antigens, respectively. The transition of straight to branched poly-LacNAc chain (i to I) is determined by the I locus, which expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC. Our previous investigation demonstrated that the i-to-I transition in erythroid differentiation is regulated by the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha). In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition is determined by the phosphorylation status of the C/EBPalpha Ser-21 residue, with dephosphorylated C/EBPalpha Ser-21 stimulating the transcription of the IGnTC gene, consequently resulting in I branching. Results from studies using adult erythropoietic and granulopoietic progenitor cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPalpha in CD34(+) hematopoietic cells demonstrating that the dephosphorylated form of C/EBPalpha Ser-21 induced the expression of I antigen, granulocytic CD15, and also erythroid CD71 antigens. Taken together, these results demonstrate that the regulation of poly-LacNAc branching (I antigen) formation in erythropoiesis and granulopoiesis share a common mechanism, with dephosphorylation of the Ser-21 residue on C/EBPalpha playing the critical role.

Expression of the histo-blood group B gene predominates in AB-genotype cells

BACKGROUND: It has been demonstrated that the 43‐bp minisatellite sequence in the 5′ region of the ABO gene plays an important role in its transcriptional regulation. It was determined in previous investigations that the structure of the minisatellite enhancer was specific to A, B, and O alleles.

Polymorphism and distribution of the Secretor α(1,2)‐fucosyltransferase gene in various Taiwanese populations

BACKGROUND: The Secretor gene (Se or FUT2), which produces α(1,2)‐fucosyltransferase, exhibits extensive polymorphism. Six Se genes, including the weak Se (Sew or Se385) and three nonsecretor alleles (se571, se685, and se849) have been detected in various populations of Taiwan. The distribution of various Lewis phenotypes among the Taiwanese population groups has been shown to vary considerably.

A novel A allele with 664G>A mutation identified in a family with the Am phenotype.

BACKGROUND:  The Am phenotype has been characterized as a weak expression of the A antigen on red blood cells but the presence of a normal quantity of the A antigen in saliva. This study describes a molecular genetic analysis of members of an Am family.

The molecular genetics of the mouse Iβ-1,6-N-acetylglucosaminyltransferase locus

The I antigen and its precursor, the i antigen, are carbohydrate structures and are found on the surface of most mammalian cells. Conversion of the i to the I structure requires I beta-1,6-N-acetylglucosaminyltransferase activity. The present investigation demonstrates a novel transcript form expressed from the mouse I locus and elucidates the molecular genetics and the genomic organization of the mouse I locus. The mouse I locus was demonstrated to express three transcript forms, one newly identified and two previously reported, which have a different exon 1 but identical exons 2 and 3. The three transcripts were shown to express differentially in various mouse tissues, and all their protein products demonstrated GlcNAc-transferring activity in enzyme function assay. The molecular genetics proposed for the mouse I locus shows that it is homologous to the human I locus. It has been established recently that a defect in the human I locus may lead to the development of congenital cataracts. It was demonstrated that the mouse and the human I transcripts expressed in the epithelium cells of the mouse and human lens, respectively, are homologous forms.