Lipoprotein(a) [Lp(a)], an atherogenic lipoprotein, consists of an LDL particle complexed with a large glycoprotein, apollpoprotein(a) [apo(a)]. Apo(a) is one of the most polymorphic expressed sequences in the human genome. The glycoprotein varies in size over a ∼500 kDa range due to length polymorphisms in the apo(a) gene. The region of the apo(a) gene responsible for this size polymorphism was cloned and characterized. Apo(a) alleles of different length were found to contain varying numbers of a subset of a tandemly-repeated, 5.5 kllobase, kringle IV-encoding sequences. A total of 34 apo(a) alleles and glycoproteins could be distinguished using pulsed-field gel electrophoresis and genomic blotting and lmmmunoblotting. Molecular analysis of a newly-generated apo(a) allele of different length suggests that the high degree of length polymorphism is in part due to recombination between sister chromatids.
ASJC Scopus subject areas
- Molecular Biology