title: The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts.
abstract: The human i and I antigens are characterized as linear and branched repeats of N-acetyllactosamine, respectively. Conversion of the i to the I structure requires I-branching beta-1,6-N-acetylglucosaminyltransferase activity. It has been noted that the null phenotype of I, the adult i phenotype, is associated with congenital cataracts in Asians. Previously, the identification of molecular changes in the IGnT gene, associated with the adult i phenotype, has been reported. In the present study, we demonstrate that the human I locus expresses 3 IGnT forms, designated IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exons 2 and 3, coding regions. The molecular genetics proposed for the I locus offer a new perspective on the formation and expression of the I antigen in different cells and provide insight into the questions derived from investigation of the adult i phenotype. Molecular genetic analyses of the I loci of the 2 adult i groups, with and without congenital cataracts, were performed, and enzyme function assays and expression patterns for the 3 IGnT transcripts in reticulocytes and lens-epithelium cells were analyzed. The results suggest a molecular genetic mechanism that may explain the partial association of the adult i phenotype with congenital cataracts and indicate that a defect in the I locus may lead directly to the development of congenital cataracts. The results also suggest that the human blood group I gene should be reassigned to the IGnTC form, not the IGnTB form, as described previously.
authors.affiliation: Transfusion Medicine Laboratory, Mackay Memorial Hospital, and the Institute of Biochemical Sciences, College of Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Lung-Chih
authors.initials: LC
authors.lastname: Yu
authors.forename: Yuh-Ching
authors.initials: YC
authors.lastname: Twu
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Chou
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
authors.forename: Alan R
authors.initials: AR
authors.lastname: Gray
authors.forename: Joann M
authors.initials: JM
authors.lastname: Moulds
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chang
authors.forename: Marie
authors.initials: M
authors.lastname: Lin
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D018076:DNA, Complementary / Q000032:analysis; D006801:Humans; D007048:I Blood-Group System / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D007908:Lens, Crystalline / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis; D012156:Reticulocytes / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan; D044465:White People
chemical_list: D018076:DNA, Complementary; D007048:I Blood-Group System; D007527:Isoenzymes; D012333:RNA, Messenger; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases