2006-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/653634摘要：人類的P血型系統已確立很長一段時間，它是29個已確認的人類血型抗原系統中第3個被發現確認的；但是P血型系統的分子遺傳學卻仍未被釐清。P血型系統僅包含一個抗原，P1。另有三個抗原，P，Pk，及LKE，和P1抗原密切相關。P1為一個醣抗原，具有Gala1-4Gala1-4GlcNAcb1-3Galb1-4Glcb1-1Cer的結構；而Pk則為Gala1-4Galb1-4Glcb1-1Cer的醣結構。P1及Pk抗原皆帶有Gala1-4的末端結構。P抗原，GalNAcb1-3Gala1-4Galb1-4Glcb1-1Cer，則可由Pk結構進一步經由GalNAc b1-3連結醣化而產生。根據這些抗原的表現與否，P血型系統共可分為五種表現型：P1 (P1+P+Pk+)，P2 (P1–P+Pk+)，P1k (P1+P–Pk+)，P2k (P1–P–Pk+)，和p (P1–P–Pk–)。在台灣人的P1表現型頻率約為32%。 P1基因應負責表現一種a-1,4-galactosyltransferase；P基因則表現一種b-1,3-N-acetylgalactosaminyltransferase。而P<br> Abstract: The P blood group system has been established for a long time and is the third system in the recognized 29 systems of human blood groups; however, its molecular genetics still awaits elucidation. The P system contains only one antigen, P1. Three additional antigens, P, Pk, and LKE, closely related to the P1 antigen, have been recognized. The P1 antigen is characterized by the carbohydrate structure Gala1-4Gala1-4GlcNAcb1-3Galb1-4Glcb1-1Cer, and the Pk has the antigenic structure Gala1-4Galb1-4Glcb1-1Cer, which also bears a Gala1-4 terminal as the P1 antigen does. The P antigen (GalNAcb1-3Gala1-4Galb1-4Glcb1-1Cer) can be produced as the Pk structure serving as a precursor. According to the expression of these antigens, five phenotypes in the P blood group are classified: P1 (P1+P+Pk+), P2 (P1–P+Pk+), P1k (P1+P–Pk+), P2k (P1–P–Pk+), and p (P1–P–Pk–). The frequency of the P1 phenotype in Taiwanese is about 32%. The P1 gene probably encodes an a-1,4-galactosyltransferase, while the P gene, which has been shown to be independent of the P1 locus, encodes a b-1,3-N-acetylgalactosaminyltransferase. The Pk gene also produces an a-1,4-galactosyltransferase; nevertheless, the relationship between the P1 and Pk genes is undetermined, as unusual correlation in P1 and Pk antigen expression has been observed: (1) Individuals with the p phenotype who lack Pk antigens also lack P1 antigen; however, individuals with the P2 or P2k phenotypes who lack P1 antigen express Pk antigen normally; (2) No P1 children were produced from the mating type P2Xp. Due to the observation of the two phenomena, the relationship between the P1 a-1,4-galactosyltransferase and the Pk a-1,4-galactosyltransferase has long been debated. Several genetic models have been proposed to explain the expression of the P1 and Pk antigens. The Pk a-1,4-galactosyltransferase gene was cloned and molecular basis of the p phenotype was demonstrated recently; however, the molecular genetic background for the correlation of the P1 and Pk antigen expression is still unrevealed. Our goal in this research project is to establish the molecular genetics of the human P blood group system. This includes identification of the P1 gene and elucidation of the molecular genetic basis for the correlation of the P1 and Pk antigen expression. Two new approaches for identification of the P1 gene are designed. We will use the SNP information in NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine) and employ the positional cloning strategy to localize the P1 gene candidate. We will also establish the B lymphocyte cell line (with the P2 phenotype) through Epstein-Barr virus (EBV) transformation and employ the expression cloning technique using the retrovirus expression system to identify the P1 gene as the established B lymphocyte cell line serving as a host cell. Our research plan includes seven main steps: (1) Assessing and collecting the typical pedigrees with P1/P2 phenotypes; (2)血型系統醣結構分子遺傳學blood group systemgalactosyltransferase