Original Investigations

Human Genetics

, Volume 79, Issue 4, pp 352-356

First online:

The apolipoprotein(a) gene resides on human chromosome 6q26–27, in close proximity to the homologous gene for plasminogen

  • Susan Lynn FrankAffiliated withDepartment of Microbiology, University of California
  • , Ivana KlisakAffiliated withDepartment of Medicine, School of Medicine, University of California
  • , Robert S. SparkesAffiliated withDepartment of Medicine, School of Medicine, University of California
  • , T. MohandasAffiliated withDivision of Medical Genetics, Harbor-UCLA Medical Center
  • , James E. TomlinsonAffiliated withDepartment of Cardiovascular Research, Genentech, Inc.
  • , John W. McLeanAffiliated withDepartment of Cardiovascular Research, Genentech, Inc.
  • , Richard M. LawnAffiliated withDepartment of Cardiovascular Research, Genentech, Inc.
  • , Aldons J. LusisAffiliated withDepartment of Microbiology, University of CaliforniaDepartment of Medicine, School of Medicine, University of California

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Summary

Apolipoprotein(a) [apo(a)], the glycoprotein associated with the lipoprotein(a) [Lp(a)] subfraction of plasma lipoproteins, has been shown to exhibit heritable molecular weight isoforms ranging from 400–700 kDa. Increased serum concentrations of Lp(a) correlate positively with the risk of atherosclerosis. Variations in Lp(a) plasma levels among individuals are inherited as a codominant quantitative trait. As part of an effect to define the basis of these variations and further clarify the expression of the protein, we have determined the chromosomal location of the human apo(a) gene. Blot hybridization analysis of DNA from a panel of mouse-human somatic cell hybrids with an apo(a) cDNA probe revealed a complex pattern of bands, all of which segregated with chromosome 6. In situ hybridization yielded a single peak of grain density located on chromosome 6q26–27. Apo(a) cDNA sequences exhibit striking homology to those of the plasma protease plasminogen, and, therefore, we have reexamined the chromosome assignment of the plasminogen gene. We conclude that both the apo(a) and plasminogen genes reside on human chromosome 6q22–27, consistent with a gene duplication mechanism for their evolutionary origin. The results are of significance for the genetic control of apo(a) expression and genetic influences predisposing to atherosclerosis.