Tangier disease. The complete mRNA sequence encoding for preproapo-A-I.
A cDNA library of Tangier liver mRNA has been established, and two apo-A-I-containing clones were identified. The complete derived amino acid sequence of preproapo-A-I has been established by nucleic acid sequence analysis of cloned apo-A-I cDNA and specific primer extensions on Tangier liver RNA. Sequence analysis of the longest cDNA clone, pMDB136T, established the derived amino acid sequence of residues 116-243 of plasma apo-A-I. The remaining portion of the sequence of Tangier preproapo-A-I mRNA was established by sequence analysis of specific primer extensions of synthetic oligonucleotides on Tangier liver mRNA. This latter technique provided the derived amino acid sequence of residues -24 to 116, thus completing the entire preproapo-A-I structure. The structure of Tangier preproapo-A-I was identical to normal preproapo-A-I except for a single base substitution (G----T) which resulted in the isosteric replacement of a glutamic acid residue at position 120 to aspartic acid. These results are interpreted as indicating that there is no major structural defect in Tangier apo-A-I, and the rapid rate of catabolism of apo-A-I in Tangier disease is due to a post-translational defect in apo-A-I metabolism.
D000595:Amino Acid Sequence; D001054:Apolipoproteins A / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004274:DNA, Recombinant; D015245:Deoxyribonuclease BamHI; D006801:Humans; D007009:Hypolipoproteinemias / Q000235:genetics*; D008099:Liver / Q000032:analysis*; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013631:Tangier Disease / Q000235:genetics*
D001054:Apolipoproteins A; D004274:DNA, Recombinant; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D012333:RNA, Messenger; C035250:preproapolipoprotein A-I; D004247:DNA; D004262:DNA Restriction Enzymes; D015245:Deoxyribonuclease BamHI