Molecular definition of the extreme size polymorphism in apolipoprotein(a)

Carolin Lackner; Jonathan C. Cohen; Helen H. Hobbs

doi:10.1093/hmg/2.7.933

Molecular definition of the extreme size polymorphism in apolipoprotein(a)

Carolin Lackner, Jonathan C. Cohen, Helen H. Hobbs

Research output: Contribution to journal › Article › peer-review

325 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	933-940
Number of pages	8
Journal	Human molecular genetics
Volume	2
Issue number	7
DOIs	https://doi.org/10.1093/hmg/2.7.933
State	Published - Jul 1993

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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title = "Molecular definition of the extreme size polymorphism in apolipoprotein(a)",

abstract = "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.",

author = "Carolin Lackner and Cohen, {Jonathan C.} and Hobbs, {Helen H.}",

note = "Funding Information: We wish to acknowledge the excellent technical assistance of Tommy Hyatt, Kathy Schueler, and Carla Leffert as well as helpful discussions with Giulia Chiesa. This work was supported by NIH HL-47619 and the Perot Family Fund. Helen H. Hobbs is an Established Investigator for the American Heart Association. Carolin Lackner is a Schroedinger Scholar.",

year = "1993",

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doi = "10.1093/hmg/2.7.933",

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AU - Cohen, Jonathan C.

AU - Hobbs, Helen H.

N1 - Funding Information: We wish to acknowledge the excellent technical assistance of Tommy Hyatt, Kathy Schueler, and Carla Leffert as well as helpful discussions with Giulia Chiesa. This work was supported by NIH HL-47619 and the Perot Family Fund. Helen H. Hobbs is an Established Investigator for the American Heart Association. Carolin Lackner is a Schroedinger Scholar.

PY - 1993/7

Y1 - 1993/7

N2 - 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.

AB - 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.

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Molecular definition of the extreme size polymorphism in apolipoprotein(a)

Abstract

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