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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, apolipoprotein(a) [apo(a)]. Apo(a) is one of the most polymorphic expressed sequences in the human genome. The glycoprotein varies in size over a approximately 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 kilobase, 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 immunoblotting. 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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Cited by
Mapping and sequencing of structural variation from eight human genomes
Kidd, J. M., Cooper, G. M., Donahue, W. F., Hayden, H. S., Sampas, N., Graves, T., Hansen, N., Teague, B., Alkan, C., Antonacci, F., et al. (2008) · Nature · doi:10.1038/nature06862 · Cited by 1,119
Fine-scale structural variation of the human genome
Tuzun, E., Sharp, A. J., Bailey, J. A., Kaul, R., Morrison, V. A., Pertz, L. M., Haugen, E., Hayden, H., Albertson, D., Pinkel, D., et al. (2005) · Nature Genetics · doi:10.1038/ng1562 · Cited by 991
Personalized copy number and segmental duplication maps using next-generation sequencing
Alkan, C., Kidd, J. M., Marques-Bonet, T., Aksay, G., Antonacci, F., Hormozdiari, F., Kitzman, J. O., Baker, C., Malig, M., Mutlu, O., et al. (2009) · Nature Genetics · doi:10.1038/ng.437 · Cited by 748
Lipoprotein(a): resurrected by genetics
Kronenberg, F., & Utermann, G. (2013) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2012.02592.x · Cited by 521
Vissers, L. E. L. M., de Vries, B. B. A., Osoegawa, K., Janssen, I. M., Feuth, T., Choy, C. O., Straatman, H., van der Vliet, W., Huys, E. H. L. P. G., van Rijk, A., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/379977 · Cited by 469
Metadata
- Authors
- Lackner, C., Cohen, J. C., & Hobbs, H. H.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1993
- Volume
- 2
- Issue
- 7
- Pages
- 933-940
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2160741225
- Cited by
- 319
- References
- 0
- FWCI
- 20.57
- Type
- journal article
- Language
- en
- Open access
- closed
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- Lackner, C., Cohen, J. C., & Hobbs, H. H. (1993). Molecular definition of the extreme size polymorphism in apolipoprotein(a). Human Molecular Genetics. https://doi.org/10.1093/hmg/2.7.933
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