TY - JOUR
T1 - Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels
AU - Mancini, Francesco P.
AU - Mooser, Vincent
AU - Guerra, Rudy
AU - Hobbs, Helen H.
N1 - Funding Information:
We wish to thank Kathy Schueler and Tommy Hyatt for their excellent technical assistance and Jonathan Cohen for helpful discussions. This work was supported by HL-20948 and the Perot Family Fund and HL-40613. H.H.H. is an Established Investigator of the American Heart Association. F.P.M. is on leave of absence from the Dipartimento di Biochimica e Biotecnologie Mediche, Facolta di Medicina, University of Naples 'Federico II', Italy. V.M. is supported by the Swiss Academy for Medical Sciences, the Ciba-Geigy Foundation and the Holderbank Foundation.
PY - 1995/9
Y1 - 1995/9
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/4.9.1535
DO - 10.1093/hmg/4.9.1535
M3 - Article
C2 - 8541836
AN - SCOPUS:0029116287
SN - 0964-6906
VL - 4
SP - 1535
EP - 1542
JO - Human molecular genetics
JF - Human molecular genetics
IS - 9
ER -