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.
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References
Birnboim HC, Doly J (1979) A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res 7:1513–1523
Breckenridge WC, Little JA, Steiner G, Chow A, Poapst M (1978) Hypertriglyceridemia associated with deficiency of apolipoprotein CII. N Engl J Med 298:1265–1272
Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212:628–635
Cox DW, Breckenridge WC, Little JA (1978) Inheritance of apolipoprotein CII deficiency with hypertriglyceridaemia and pancreatitis. N Engl J Med 299:1421–1424
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 250–254
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)
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 74:1942–1945
Jeffreys AJ, Flavell RA (1977) A physical map of the DNA regions flanking the rabbit β globin gene. Cell 12:429–439
Karathanasis SK, Zannis VI, Breslow JL (1983) Isolation and characterization of the human apolipoprotein A-I gene. Proc Natl Acad Sci USA 80:6147–6151
Kostner G, Holasek A (1972) Characterisation and quantitation of the apolipoproteins from human chyle chylomicrons. Biochemistry 11:1217–1223
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 74:1245–1249
La Rosa JC, Levy RI, Herbert P, Lux SE, Fredrickson DS (1970) Specific apoprotein activator for lipoprotein lipase. Biochem Biophys Res Commun 41:57–62
Marsh JB (1976) Apoproteins of the lipoproteins in a nonrecirculating perfusate of rat liver. J Lipid Res 17:85–90
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 11:69–76
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 259:4401–4404
Ott J (1974) Estimation of the recombinant fraction in human pedigrees: efficient computation of the likelihood for human studies. Am J Hum Genet 26:588–597
Schonfeld G, Grimme N, Alpers D (1980) Detection of apolipoprotein C in human and rat enterocytes. J Cell Biol 86:562–567
Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
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 30:919–926
Talmadge K, Stahl S, Gilbert W (1980) Eukaryotic signal sequence transports insulin antigen in E. Coli. Proc Natl Acad Sci USA 77:3369–3373
Wu A-L, Windmueller HG (1979) Relative contributions by liver and intestine to individual plasma apolipoproteins in the rat. J Biol Chem 254:7316–7322
Yamamura T, Sudo H, Ishikawa K, Yamamoto A (1979) Familial type I hyperlipoproteinemia caused by apolipoprotein CII deficiency. Atherosclerosis 34:53–65
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Humphries, S.E., Williams, L., Myklebost, O. et al. Familial apolipoprotein CII deficiency: A preliminary analysis of the gene defect in two independent families. Hum Genet 67, 151–155 (1984). https://doi.org/10.1007/BF00272990
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DOI: https://doi.org/10.1007/BF00272990