Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels

Francesco P. Mancini, Vincent Mooser, Rudy Guerra, Helen H. Hobbs

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Lipoprotein(a) [Lp(a)] is a cholesterol ester-rich atherogenic lipoprotein that is composed of a particle of low density lipoprotein and a large glycoprotein, apolipoprotein(a) [apo(a)]. Apolipoprotein(a) varies in size over a ̃500 kDa range due to inter-allelic differences in the number of tandemly repeated kringle 4 (K4)-encoding 5. 5 kb sequences in the apo(a) gene. Only one of the 10 different types of K4 repeats in the apo(a) gene, the so-called type 2 K4 repeats, vary in number between apo(a) alleles. In this paper, we show that there is microheterogeneity within the sequence of the type 2 K4 repeat. Dralll restriction digestion and genomic blotting revealed that a subset of the type 2 K4-encoding sequences contained a Dralll site (K4-D). The proportion of apo(a) alleles that had at least one K4-D repeat ranged from 25% in Caucasians to 50% in the Chinese. K4-D repeats were clustered at the end(s) of the type 2 K4 tandem array and the number and patterns of the K4-D repeats were in linkage disequilibrium with flanking sequence polymorphisms; these features are remarkably similar to the minisatellite variant repeats (MVRs) found in variable number of tandem repeat sequences (VNTRs). In addition, a Dralll pattern that comprised 9% of the sample was invariably associated with low plasma levels of Lp(a) in Caucasians.

Original languageEnglish (US)
Pages (from-to)1535-1542
Number of pages8
JournalHuman Molecular Genetics
Volume4
Issue number9
DOIs
StatePublished - Sep 1995

Fingerprint

Kringles
Apoprotein(a)
Lipoproteins
Lipoprotein(a)
Plasma
Genes
Gene
Plasmas
Encoding
Vary
Linkage Disequilibrium
Minisatellite Repeats
Glycoprotein
Cholesterol
Polymorphism
Glycoproteins
Genomics
Proportion
Alleles
Relationships

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)
  • Genetics

Cite this

Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels. / Mancini, Francesco P.; Mooser, Vincent; Guerra, Rudy; Hobbs, Helen H.

In: Human Molecular Genetics, Vol. 4, No. 9, 09.1995, p. 1535-1542.

Research output: Contribution to journalArticle

Mancini, Francesco P. ; Mooser, Vincent ; Guerra, Rudy ; Hobbs, Helen H. / Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels. In: Human Molecular Genetics. 1995 ; Vol. 4, No. 9. pp. 1535-1542.
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