HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cox, L. A. Articles by Hixson, J. E. Search for Related Content PubMed PubMed Citation Articles by Cox, L. A. Articles by Hixson, J. E. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 39, 1319-1326, July 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Molecular basis of an apolipoprotein[a] null allele: a splice site mutation is associated with deletion of a single exon

Correspondence to: James E. Hixson.

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.—Cox, L. A., C. Jett, and J. E. Hixson. Molecular basis of an apolipoprotein[a] null allele: a splice site mutation is associated with deletion of a single exon. J. Lipid Res. 1998. 39: 1319–1326.

Supplementary key words: protein secretion, plasminogen, lipid metabolism, transcript processing

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. A. Cox, S. Birnbaum, M. C. Mahaney, D. L. Rainwater, J. T. Williams, and J. L. VandeBerg Identification of Promoter Variants in Baboon Endothelial Lipase That Regulate High-Density Lipoprotein Cholesterol Levels Circulation, September 4, 2007; 116(10): 1185 - 1195. [Abstract] [Full Text] [PDF]

				J. Wang, J. Boedeker, H. H. Hobbs, and A. L. White Determinants of human apolipoprotein [a] secretion from mouse hepatocyte cultures J. Lipid Res., January 1, 2001; 42(1): 60 - 69. [Abstract] [Full Text]

				G. Lippi and G. Guidi Lipoprotein(a): from ancestral benefit to modern pathogen? QJM, February 1, 2000; 93(2): 75 - 84. [Abstract] [Full Text] [PDF]

				J. Wang and A. L. White 6-Aminohexanoic Acid as a Chemical Chaperone for Apolipoprotein(a) J. Biol. Chem., April 30, 1999; 274(18): 12883 - 12889. [Abstract] [Full Text] [PDF]