Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Dec 1;89(23):11584–11588. doi: 10.1073/pnas.89.23.11584

Characterization by yeast artificial chromosome cloning of the linked apolipoprotein(a) and plasminogen genes and identification of the apolipoprotein(a) 5' flanking region.

N Malgaretti 1, F Acquati 1, P Magnaghi 1, L Bruno 1, M Pontoglio 1, M Rocchi 1, S Saccone 1, G Della Valle 1, M D'Urso 1, D LePaslier 1, et al.
PMCID: PMC50597  PMID: 1454851

Abstract

The apoprotein(a) [apo(a)] gene encodes a protein component of the circulating lipoprotein(a) [Lp(a)]. The apo(a) gene is highly homologous to the plasminogen gene. It encodes one of the most polymorphic human proteins, due to variability in the number of repetitions of structures called kringles. In addition, Lp(a) levels vary among individuals by more than two orders of magnitude, the high levels being highly correlated with predisposition to early atherosclerotic disease. To better understand the genetics and function of the apo(a) gene, we have cloned in yeast artificial chromosome vectors DNA fragments comprising the linked apo(a) and plasminogen genes and other members of the plasminogen family. By a combination of pulsed-field gel electrophoresis and genome walking experiments, we have identified the 5' portion and flanking regions of the apo(a) gene.

Full text

PDF
11584

Images in this article

11585Image
on p.11585
11585Image
on p.11585
11586Image
on p.11586
11587Image
on p.11587

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albertsen H. M., Abderrahim H., Cann H. M., Dausset J., Le Paslier D., Cohen D. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4256–4260. doi: 10.1073/pnas.87.11.4256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armstrong V. W., Cremer P., Eberle E., Manke A., Schulze F., Wieland H., Kreuzer H., Seidel D. The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis. 1986 Dec;62(3):249–257. doi: 10.1016/0021-9150(86)90099-7. [DOI] [PubMed] [Google Scholar]
  3. Brown M. S., Goldstein J. L. Plasma lipoproteins: teaching old dogmas new tricks. Nature. 1987 Nov 12;330(6144):113–114. doi: 10.1038/330113a0. [DOI] [PubMed] [Google Scholar]
  4. Burke D. T., Carle G. F., Olson M. V. Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science. 1987 May 15;236(4803):806–812. doi: 10.1126/science.3033825. [DOI] [PubMed] [Google Scholar]
  5. Frank S. L., Klisak I., Sparkes R. S., Lusis A. J. A gene homologous to plasminogen located on human chromosome 2q11-p11. Genomics. 1989 Apr;4(3):449–451. doi: 10.1016/0888-7543(89)90356-x. [DOI] [PubMed] [Google Scholar]
  6. Frank S. L., Klisak I., Sparkes R. S., Mohandas T., Tomlinson J. E., McLean J. W., Lawn R. M., Lusis A. J. The apolipoprotein(a) gene resides on human chromosome 6q26-27, in close proximity to the homologous gene for plasminogen. Hum Genet. 1988 Aug;79(4):352–356. doi: 10.1007/BF00282175. [DOI] [PubMed] [Google Scholar]
  7. Ichinose A. Multiple members of the plasminogen-apolipoprotein(a) gene family associated with thrombosis. Biochemistry. 1992 Mar 31;31(12):3113–3118. doi: 10.1021/bi00127a011. [DOI] [PubMed] [Google Scholar]
  8. Kamboh M. I., Ferrell R. E., Kottke B. A. Expressed hypervariable polymorphism of apolipoprotein (a). Am J Hum Genet. 1991 Nov;49(5):1063–1074. [PMC free article] [PubMed] [Google Scholar]
  9. Lackner C., Boerwinkle E., Leffert C. C., Rahmig T., Hobbs H. H. Molecular basis of apolipoprotein (a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest. 1991 Jun;87(6):2153–2161. doi: 10.1172/JCI115248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lindahl G., Gersdorf E., Menzel H. J., Seed M., Humphries S., Utermann G. Variation in the size of human apolipoprotein(a) is due to a hypervariable region in the gene. Hum Genet. 1990 May;84(6):563–567. doi: 10.1007/BF00210810. [DOI] [PubMed] [Google Scholar]
  11. Little R. D., Porta G., Carle G. F., Schlessinger D., D'Urso M. Yeast artificial chromosomes with 200- to 800-kilobase inserts of human DNA containing HLA, V kappa, 5S, and Xq24-Xq28 sequences. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1598–1602. doi: 10.1073/pnas.86.5.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McLean J. W., Tomlinson J. E., Kuang W. J., Eaton D. L., Chen E. Y., Fless G. M., Scanu A. M., Lawn R. M. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987 Nov 12;330(6144):132–137. doi: 10.1038/330132a0. [DOI] [PubMed] [Google Scholar]
  13. Petersen T. E., Martzen M. R., Ichinose A., Davie E. W. Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem. 1990 Apr 15;265(11):6104–6111. [PubMed] [Google Scholar]
  14. Rocchi M., Roncuzzi L., Santamaria R., Archidiacono N., Dente L., Romeo G. Mapping through somatic cell hybrids and cDNA probes of protein C to chromosome 2, factor X to chromosome 13, and alpha 1-acid glycoprotein to chromosome 9. Hum Genet. 1986 Sep;74(1):30–33. doi: 10.1007/BF00278781. [DOI] [PubMed] [Google Scholar]
  15. Scott J. Lipoprotein(a). Thrombogenesis linked to atherogenesis at last? Nature. 1989 Sep 7;341(6237):22–23. doi: 10.1038/341022a0. [DOI] [PubMed] [Google Scholar]
  16. Utermann G., Duba C., Menzel H. J. Genetics of the quantitative Lp(a) lipoprotein trait. II. Inheritance of Lp(a) glycoprotein phenotypes. Hum Genet. 1988 Jan;78(1):47–50. doi: 10.1007/BF00291233. [DOI] [PubMed] [Google Scholar]
  17. Utermann G., Kraft H. G., Menzel H. J., Hopferwieser T., Seitz C. Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of LP(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum Genet. 1988 Jan;78(1):41–46. doi: 10.1007/BF00291232. [DOI] [PubMed] [Google Scholar]
  18. Utermann G. The mysteries of lipoprotein(a). Science. 1989 Nov 17;246(4932):904–910. doi: 10.1126/science.2530631. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES