Summary
The apolipoprotein B gene is subject to mutations that may be important in coronary heart diseases. We have used polymerase chain reaction and denaturin gradient gel electrophoresis to characterize a single nucleotide substitution in the apolipoprotein B gene. This mutation affects amino acid 4311 of the protein and converts asparagine to serine. It was found in 24% of the 81 unrelated individuals analyzed. Moreover, another mutation was detected by sequencing in a single individual.
This is a preview of subscription content, log in via an institution to check access.
References
Blackhart BD, Ludwig EM, Perotti VR, Caiati L, Onasch MA, Wallis SC, Powell L, Pease R, Knott TJ, Chu Mon-Li, Mahley RW, Scott J, McCarthy BJ, Levy-Wilson B (1986) Structure of the human apolipoprotein B gene. J Biol Chem 261:15364–15367
Brown MS, Goldstein JL (1983) Familial hypercholestcrolaemia. In: Stanbury MS, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited human disease. McGraw-Hill, New York, pp 500–550
Fischer SG, Lerman LS (1983) DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: correspondance with melting theory. Proc Natl Acad Sci USA 80:1579–1583
Knott TS, Pease RJ, Powell LH, Wallis SC, Rall SC, Innerarity TL, Blackhart B, Taylor WR, Lusis AJ, McCarthy BJ, Mahley RW, Levy-Wilson B, Scott J (1986) Human apolipoprotein B: complete cDNA sequence and identification of structural domains of the protein. Nature 323:734–738
Law A, Wallis SC, Powell LM, Pease RJ, Brunt H, Priestley LM, Knott JJ, Scott J, Altman DG, Miller GJ, Rajput J, Miller NE (1986a) Common DNA polymorphism within coding sequence of apolipoprotein B gene associated with altered lipid levels. Lancet I:1301–1303
Law SW, Grant SM, Higuchi K, Hospattankar A, Lackner K, Lee N, Brewer HB (1986b) Human liver apolipoprotein B-100 DNA: complete nucleic acid and derived amino acid sequence. Proc Natl Acad Sci USA 83:8142–8146
Messing J (1983) New M13 vectors for cloning. Methods Enzymol 101:20–78
Myers RM, Fischer SG, Maniatis T, Lerman LS (1985) Modification of the melting properties of duplex DNA by denaturing gradient gel electrophoresis. Nucleic Acids Res 13:3111–3129
Noll WW, Collins M (1987) Detection of human DNA polymorphisms with a simplified denaturing gradient gel electrophoresis technique. Proc Natl Acad Sci USA 84:3339–3343
Saiki RK, Scharf S, Faloona S, Mullis F, Horn KB, Erlich GT, Arnheim N (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
Sheffield VC, Cox DR, Lerman LS, Myers RM (1989) Attachment of a 40-base pair G + C rich requence (GC clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc Natl Acad Sci USA 86:232–236
Tabor S, Richardson CC (1987) DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci USA 84:4767–4771
Traystman MD, Higuchi M, Kasper CK, Antonarakis SE, Kazazian HH Jr (1990) Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene. Genomics 6:293–301
Yan CY, Chen SH, Sparrow JT, Gianturco SH, Bradley WA, animura M, Li WH, Sparrow DA, De Loof H, Rosseneu M, Proot L, Brasseur B, Ruysschaert JM, Lee FS, Gu ZW, Gotto AM Jr, Chan L (1986) The primary structure and structure-function relationships of human apolipoprotein B-100, a colossal protein with numerous internal repeats. Nature 323:738–742
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Navajas, M., Laurent, AM., Moreel, JF. et al. Detection by denaturing gradient gel electrophoresis of a new polymorphism in the apolipoprotein B gene. Hum Genet 86, 91–93 (1990). https://doi.org/10.1007/BF00205183
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00205183