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Human Genetics

, Volume 67, Issue 2, pp 151–155 | Cite as

Familial apolipoprotein CII deficiency: A preliminary analysis of the gene defect in two independent families

  • S. E. Humphries
  • L. Williams
  • O. Myklebost
  • A. F. H. Stalenhoef
  • P. N. M. Demacker
  • G. Baggio
  • G. Crepaldi
  • D. J. Galton
  • R. Williamson
Original Investigations

Summary

We have used a cDNA clone for human apolipoprotein CII (apo CII) to study the apo CII genes in two independent individuals with familial apo CII deficiency. With all the restriction enzymes so far used, gene fragments hybridising with apo CII cDNA are observed that are indistinguishable from normal samples. This demonstrates that in neither of these individuals is the defect due to a major deletion of DNA in or around the apo CII gene. We have used a common polymorphism of the apo CII gene detected with the enzyme TaqI to follow the inheritance of the gene in the families of these apo CII deficient individuals. The pattern of inheritance that we observe is consistent with the defect causing apo CII deficiency being in, or closely linked to the apo CII structural gene.

Keywords

Restriction Enzyme Metabolic Disease Structural Gene Preliminary Analysis cDNA Clone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Birnboim HC, Doly J (1979) A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res 7:1513–1523Google Scholar
  2. Breckenridge WC, Little JA, Steiner G, Chow A, Poapst M (1978) Hypertriglyceridemia associated with deficiency of apolipoprotein CII. N Engl J Med 298:1265–1272Google Scholar
  3. Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212:628–635Google Scholar
  4. Cox DW, Breckenridge WC, Little JA (1978) Inheritance of apolipoprotein CII deficiency with hypertriglyceridaemia and pancreatitis. N Engl J Med 299:1421–1424Google Scholar
  5. Crepaldi G, Feilin R, Baggio G, Augustin J, Greten H (1980) Lipoprotein and apoprotein, adipose tissue and hepatic lipoprotein lipases levels in patients with familial hyperchylomicronemia and their immediate family members. In: Gotto AM, Smith LC, Allen B (eds) Atherosclerosis V. Springer, Berlin, pp 250–254Google Scholar
  6. Humphries SE, Jowett NI, Williams L, Rees A, Vella M, Kessling A, Myklebost O, Lydon A, Seed M, Galton DJ, Williamson R (1984) A DNA polymorphism adjacent to the human apolipoprotein CII gene. Mol Biol Med (in press)Google Scholar
  7. Jackson RL, Baker HN, Gilliam EB, Gotto AM (1977) Primary structure of very low density apolipoprotein CII of human plasma. Proc Natl Acad Sci USA 74:1942–1945Google Scholar
  8. Jeffreys AJ, Flavell RA (1977) A physical map of the DNA regions flanking the rabbit β globin gene. Cell 12:429–439Google Scholar
  9. Karathanasis SK, Zannis VI, Breslow JL (1983) Isolation and characterization of the human apolipoprotein A-I gene. Proc Natl Acad Sci USA 80:6147–6151Google Scholar
  10. Kostner G, Holasek A (1972) Characterisation and quantitation of the apolipoproteins from human chyle chylomicrons. Biochemistry 11:1217–1223Google Scholar
  11. Kunkel LM, Smith DK, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW Jr, Rary JM (1977) Analysis of Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249Google Scholar
  12. La Rosa JC, Levy RI, Herbert P, Lux SE, Fredrickson DS (1970) Specific apoprotein activator for lipoprotein lipase. Biochem Biophys Res Commun 41:57–62Google Scholar
  13. Marsh JB (1976) Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver. J Lipid Res 17:85–90Google Scholar
  14. Miller NE, Rao SN, Alaupovic P, Noble N, Slack J, Brunzell JD, Lewis B (1981) Familial apolipoprotein CII deficiency: plasma lipoproteins and apolipoproteins in heterozygous and homozygous subjects and the effects of plasma infusion. Eur J Clin Invest 11:69–76Google Scholar
  15. Myklebost O, Williamson R, Markham AF, Myklebost S, Rogers J, Woods DE, Humphries SE (1984) The isolation and characterisation of cDNA clones for human apolipoprotein CII. J Biol Chem 259:4401–4404Google Scholar
  16. Ott J (1974) Estimation of the recombinant fraction in human pedigrees: efficient computation of the likelihood for human studies. Am J Hum Genet 26:588–597Google Scholar
  17. Schonfeld G, Grimme N, Alpers D (1980) Detection of apolipoprotein C in human and rat enterocytes. J Cell Biol 86:562–567Google Scholar
  18. Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517Google Scholar
  19. Stalenhoef AFH, Casparie AF, Demacker PNM, Stouten JTJ, Lutterman JA, Van 't Laar A (1981) Combined deficiency of apolipoprotein CII and lipoprotein lipase in familial hyperchylomicronemia. Metabolism 30:919–926Google Scholar
  20. Talmadge K, Stahl S, Gilbert W (1980) Eukaryotic signal sequence transports insulin antigen in E. Coli. Proc Natl Acad Sci USA 77:3369–3373Google Scholar
  21. Wu A-L, Windmueller HG (1979) Relative contributions by liver and intestine to individual plasma apolipoproteins in the rat. J Biol Chem 254:7316–7322Google Scholar
  22. Yamamura T, Sudo H, Ishikawa K, Yamamoto A (1979) Familial type I hyperlipoproteinemia caused by apolipoprotein CII deficiency. Atherosclerosis 34:53–65Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • S. E. Humphries
    • 1
  • L. Williams
    • 2
  • O. Myklebost
    • 1
  • A. F. H. Stalenhoef
    • 3
  • P. N. M. Demacker
    • 3
  • G. Baggio
    • 4
  • G. Crepaldi
    • 4
  • D. J. Galton
    • 2
  • R. Williamson
    • 1
  1. 1.Department of BiochemistrySt. Mary's Hospital Medical SchoolLondonEngland
  2. 2.Medical Professorial UnitSt. Bartholomew's Hospital Medical SchoolLondonEngland
  3. 3.Department of Medicine, Division of General Internal MedicineUniversity of NijmegenThe Netherlands
  4. 4.Department of Internal MedicineUniversity of PaduaPadovaItaly

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