Molecular basis of an apolipoprotein[a] null allele: a splice site mutation is associated with deletion of a single exon
| Autor: | L A, Cox, C, Jett, J E, Hixson |
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| Rok vydání: | 1998 |
| Předmět: |
Base Sequence
Transcription Genetic Cloning Organism Molecular Sequence Data Plasminogen Exons Apoprotein(a) Macaca mulatta Polymerase Chain Reaction Introns Alternative Splicing Apolipoproteins Liver Sequence Homology Nucleic Acid Animals Humans Amino Acid Sequence RNA Messenger Sequence Alignment Alleles DNA Primers Lipoprotein(a) Papio Sequence Deletion |
| Zdroj: | Journal of lipid research. 39(7) |
| ISSN: | 0022-2275 |
| Popis: | Apolipoprotein[a] (apo[a]), a unique component of atherogenic lipoprotein[a], is highly polymorphic in human and nonhuman primates. Null alleles, producing no detectable circulating Lp[a] or apo[a] isoforms, are found at high frequencies. The molecular basis of null alleles is not yet known. In baboons, approximately two-thirds of null alleles do not produce detectable hepatic transcripts (transcript negative nulls), and one-third of null alleles produce normal amounts of apo[a] transcripts (transcript positive nulls). We have cloned apo[a] cDNA from a baboon carrying a transcript positive null allele defective in secretion from primary hepatocytes. Compared with wild-type cDNA, the null allele contained an in-frame 47 amino acid deletion in the protease domain corresponding to one exon of the apo[a] gene. The null allele contains an A--T substitution in the third nucleotide position of the intron downstream of the deleted exon which alters the donor splice site consensus sequence. Thus, this null is likely due to a mutation that prevents normal mRNA splicing, yielding a shortened protein that may be defective in intramolecular interactions required for normal processing and secretion of apo[a]. This is the first report of a molecular basis for apo[a] null alleles. |
| Databáze: | OpenAIRE |
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