title: Variation in the size of human apolipoprotein(a) is due to a hypervariable region in the gene.
abstract: We have investigated whether the size heterogeneity of the human apolipoprotein(a) [apo(a)] is due to differences in the number of plasminogen kringle 4-like repeat units present in the different alleles. Using the Southern blot hybridization technique and a DNA probe for the kringle 4 domain of plasminogen, we have observed that in 31 different individuals a 5.8-kb PvuII restriction fragment band varies widely in intensity relative to other bands. A strong correlation (r = 0.76, P less than 0.001) was found between apo(a) protein size and the variation in intensity of the detected restriction fragment band. We confirmed this correlation in a large family where the parents are heterozygous for the apo(a) protein size isoforms. The specificity of the 5.8-kb band was established by using an apo(a)-specific oligonucleotide. These correlations strongly suggest that the observed size heterogeneity in apo(a) protein is due to different numbers of copies of the kringle 4 sequence in the apo(a) glycoprotein gene.
authors.affiliation: Charing Cross Sunley Research Center, Hammersmith, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Lindahl
authors.forename: E
authors.initials: E
authors.lastname: Gersdorf
authors.forename: H J
authors.initials: HJ
authors.lastname: Menzel
authors.forename: M
authors.initials: M
authors.lastname: Seed
authors.forename: S
authors.initials: S
authors.lastname: Humphries
authors.forename: G
authors.initials: G
authors.lastname: Utermann
mesh_terms: D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics* / Q000648:ultrastructure; D001483:Base Sequence; D015139:Blotting, Southern; D015342:DNA Probes; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics*; D010641:Phenotype; D010958:Plasminogen / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D001054:Apolipoproteins A; D015342:DNA Probes; D010446:Peptide Fragments; D010958:Plasminogen