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Nucleic Acids Res. 1982 September 25; 10(18): 5421–5427.
PMCID: PMC320886

mRNA-deficient beta o-thalassemia results from a single nucleotide deletion.

Abstract

The beta-globin gene of a patient with mRNA-deficient beta o-thalassemia has been sequenced. We find a single nucleotide deletion in amino acid codon 44 that produces a UGA terminator at codon 60. We have previously shown that the beta-globin mRNA of this patient is correctly spliced and polyadenylated, but rapidly turns over with a half-life of less than 30 min. We suggest that the rapid mRNA turnover is influenced by the deletion of this single nucleotide as well as by the nonsense codon.

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Selected References

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  • Orkin SH, Old JM, Weatherall DJ, Nathan DG. Partial deletion of beta-globin gene DNA in certain patients with beta 0-thalassemia. Proc Natl Acad Sci U S A. 1979 May;76(5):2400–2404. [PubMed]
  • Maquat LE, Kinniburgh AJ, Beach LR, Honig GR, Lazerson J, Ershler WB, Ross J. Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with beta+-thalassemia. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4287–4291. [PubMed]
  • Kantor JA, Turner PH, Nienhuis AW. Beta Thalassemia: mutations which affect processing of the beta-Globin mRNA precursor. Cell. 1980 Aug;21(1):149–157. [PubMed]
  • Spritz RA, Jagadeeswaran P, Choudary PV, Biro PA, Elder JT, deRiel JK, Manley JL, Gefter ML, Forget BG, Weissman SM. Base substitution in an intervening sequence of a beta+-thalassemic human globin gene. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2455–2459. [PubMed]
  • Westaway D, Williamson R. An intron nucleotide sequence variant in a cloned beta +-thalassaemia globin gene. Nucleic Acids Res. 1981 Apr 24;9(8):1777–1788. [PMC free article] [PubMed]
  • Busslinger M, Moschonas N, Flavell RA. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron. Cell. 1981 Dec;27(2 Pt 1):289–298. [PubMed]
  • Baird M, Driscoll C, Schreiner H, Sciarratta GV, Sansone G, Niazi G, Ramirez F, Bank A. A nucleotide change at a splice junction in the human beta-globin gene is associated with beta 0-thalassemia. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4218–4221. [PubMed]
  • Maquat LE, Kinniburgh AJ, Rachmilewitz EA, Ross J. Unstable beta-globin mRNA in mRNA-deficient beta o thalassemia. Cell. 1981 Dec;27(3 Pt 2):543–553. [PubMed]
  • Chang JC, Kan YW. beta 0 thalassemia, a nonsense mutation in man. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2886–2889. [PubMed]
  • Trecartin RF, Liebhaber SA, Chang JC, Lee KY, Kan YW, Furbetta M, Angius A, Cao A. beta zero thalassemia in Sardinia is caused by a nonsense mutation. J Clin Invest. 1981 Oct;68(4):1012–1017. [PMC free article] [PubMed]
  • Orkin SH, Goff SC. Nonsense and frameshift mutations in beta 0-thalassemia detected in cloned beta-globin genes. J Biol Chem. 1981 Oct 10;256(19):9782–9784. [PubMed]
  • Gorski J, Fiori M, Mach B. A new nonsense mutation as the molecular basis for beta thalassaemia. J Mol Biol. 1982 Jan 25;154(3):537–540. [PubMed]
  • Moschonas N, de Boer E, Grosveld FG, Dahl HH, Wright S, Shewmaker CK, Flavell RA. Structure and expression of a cloned beta o thalassaemic globin gene. Nucleic Acids Res. 1981 Sep 11;9(17):4391–4401. [PMC free article] [PubMed]
  • Ramirez F, Starkman D, Bank A, Kerem H, Cividalli G, Rachmilewitz EA. Absence of beta mRNA in beta0-thalassemia in Kurdish Jews. Blood. 1978 Oct;52(4):735–739. [PubMed]
  • Murray NE, Brammar WJ, Murray K. Lambdoid phages that simplify the recovery of in vitro recombinants. Mol Gen Genet. 1977 Jan 7;150(1):53–61. [PubMed]
  • Maniatis T, Hardison RC, Lacy E, Lauer J, O'Connell C, Quon D, Sim GK, Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. [PubMed]
  • Blattner FR, Blechl AE, Denniston-Thompson K, Faber HE, Richards JE, Slightom JL, Tucker PW, Smithies O. Cloning human fetal gamma globin and mouse alpha-type globin DNA: preparation and screening of shotgun collections. Science. 1978 Dec 22;202(4374):1279–1284. [PubMed]
  • Benton WD, Davis RW. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. [PubMed]
  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PubMed]
  • Norvell WA, Frink CR, Hill DE. Phosphorus in Connecticut lakes predicted by land use. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5426–5429. [PubMed]
  • Adhya S, Gottesman M. Control of transcription termination. Annu Rev Biochem. 1978;47:967–996. [PubMed]
  • Perry RP, Kelley DE, LaTorre J. Synthesis and turnover of nuclear and cytoplasmic polyadenylic acid in mouse L cells. J Mol Biol. 1974 Jan 25;82(3):315–331. [PubMed]
  • Zähringer J, Baliga BS, Munro HN. Novel mechanism for translational control in regulation of ferritin synthesis by iron. Proc Natl Acad Sci U S A. 1976 Mar;73(3):857–861. [PubMed]
  • Kinniburgh AJ, McMullen MD, Martin TE. Distribution of cytoplasmic poly(A+)RNA sequences in free messenger ribonucleoprotein and polysomes of mouse ascites cells. J Mol Biol. 1979 Aug 25;132(4):695–708. [PubMed]
  • McMullen MD, Shaw PH, Martin TE. Characterization of poly(A+)RNA in free messenger ribonucleoprotein and polysomes of mouse Taper ascites cells. J Mol Biol. 1979 Aug 25;132(4):679–694. [PubMed]
  • Gander ES, Stewart AG, Morel CM, Scherrer K. Isolation and characterization of ribosome-free cytoplasmic messenger-ribonucleoprotein complexes from avian erythroblasts. Eur J Biochem. 1973 Oct 18;38(3):443–452. [PubMed]
  • Stahl H, Gallwitz D. Fate of histone messenger RNA in synchronized HeLa cells in the absence of initiation of protein synthesis. Eur J Biochem. 1977 Jan;72(2):385–392. [PubMed]
  • Traeger J, Wood WG, Clegg JB, Weatherall DJ. Defective synthesis of HbE is due to reduced levels of beta E mRNA. Nature. 1980 Dec 4;288(5790):497–499. [PubMed]
  • Adams JG, 3rd, Steinberg MH, Newman MV, Morrison WT, Benz EJ, Jr, Iyer R. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0]. Proc Natl Acad Sci U S A. 1981 Jan;78(1):469–473. [PubMed]
  • Cohen-Solal M, Blouquit Y, Garel MC, Thillet J, Gaillard L, Creyssel R, Gibaud A, Rosa J. Haemoglobin Lyon (beta17-18 (A 14-15) Lys-Val leads to O). Determination by sequenator analysis. Biochim Biophys Acta. 1974 Jun 7;351(2):306–316. [PubMed]
  • Brimhall B, Jones RT, Schneider RG, Hosty TS, Tomlin G, Atkins R. Two new hemoglobins. Hemoglobin Alabama (beta39(C5)Gln leads to Lys) and hemoglobin Montgomery (alpha 48(CD 6) Leu leads to Arg). Biochim Biophys Acta. 1975 Jan 30;379(1):28–32. [PubMed]
  • Mellon P, Parker V, Gluzman Y, Maniatis T. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system. Cell. 1981 Dec;27(2 Pt 1):279–288. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press