SEQUENCE MICROHETEROGENEITY IN APOLIPOPROTEIN(A) GENE REPEATS AND THERELATIONSHIP TO PLASMA LP(A) LEVELS

Citation
Fp. Mancini et al., SEQUENCE MICROHETEROGENEITY IN APOLIPOPROTEIN(A) GENE REPEATS AND THERELATIONSHIP TO PLASMA LP(A) LEVELS, Human molecular genetics, 4(9), 1995, pp. 1535-1542
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity",Biology
Journal title
ISSN journal
0964-6906
Volume
4
Issue
9
Year of publication
1995
Pages
1535 - 1542
Database
ISI
SICI code
0964-6906(1995)4:9<1535:SMIAGR>2.0.ZU;2-1
Abstract
Lipoprotein(a) [Lp(a)] is a cholesterol ester-rich atherogenic lipopro tein that is composed of a particle of low density lipoprotein and a l arge glycoprotein, apolipoprotein(a) [apo(a)]. Apolipoprotein(a) varie s in size over a similar to 500 kDa range due to inter-allelic differe nces 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 K 4 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 m icroheterogeneity within the sequence of the type 2 K4 repeat. DraIII restriction digestion and genomic blotting revealed that a subset of t he type 2 K4-encoding sequences contained a DraIII site (K4-D). The pr oportion of apo(a) alleles that had at least one K4-D repeat ranged fr om 25% in Caucasians to 50% in the Chinese, K4-D repeats were clustere d at the end(s) of the type 2 K4 tandem array and the number and patte rns of the K4-D repeats were in linkage disequilibrium with flanking s equence polymorphisms; these features are remarkably similar to the mi nisatellite variant repeats (MVRs) found in variable number of tandem repeat sequences (VNTRs). In addition, a DraIII pattern that comprised 9% of the sample was invariably associated with low plasma levels of Lp(a) in Caucasians.