Base substitution in an intervening sequence of a β +-thalassemic human globin gene

R. A. Spritz, P. Jagadeeswaran, Prabhakara V Choudary, P. A. Biro, J. T. Elder, J. K. deRiel, J. L. Manley, M. L. Gefter, B. G. Forget, S. M. Weissman

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

β globin gene fragments from a patient with homozygous β +-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro transcription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the β +-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of β globin mRNA precursor molecules in β +-thalassemia.

Original languageEnglish (US)
Pages (from-to)2455-2459
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number4 II
DOIs
StatePublished - 1981
Externally publishedYes

Fingerprint

Globins
Introns
Thalassemia
Genes
Restriction Mapping
RNA Splice Sites
RNA Precursors
DNA Restriction Enzymes
Sequence Analysis
Nucleotides
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Spritz, R. A., Jagadeeswaran, P., Choudary, P. V., Biro, P. A., Elder, J. T., deRiel, J. K., ... Weissman, S. M. (1981). Base substitution in an intervening sequence of a β +-thalassemic human globin gene. Proceedings of the National Academy of Sciences of the United States of America, 78(4 II), 2455-2459. https://doi.org/10.1073/pnas.78.4.2455

Base substitution in an intervening sequence of a β +-thalassemic human globin gene. / Spritz, R. A.; Jagadeeswaran, P.; Choudary, Prabhakara V; Biro, P. A.; Elder, J. T.; deRiel, J. K.; Manley, J. L.; Gefter, M. L.; Forget, B. G.; Weissman, S. M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 78, No. 4 II, 1981, p. 2455-2459.

Research output: Contribution to journalArticle

Spritz, RA, Jagadeeswaran, P, Choudary, PV, Biro, PA, Elder, JT, deRiel, JK, Manley, JL, Gefter, ML, Forget, BG & Weissman, SM 1981, 'Base substitution in an intervening sequence of a β +-thalassemic human globin gene', Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 4 II, pp. 2455-2459. https://doi.org/10.1073/pnas.78.4.2455
Spritz, R. A. ; Jagadeeswaran, P. ; Choudary, Prabhakara V ; Biro, P. A. ; Elder, J. T. ; deRiel, J. K. ; Manley, J. L. ; Gefter, M. L. ; Forget, B. G. ; Weissman, S. M. / Base substitution in an intervening sequence of a β +-thalassemic human globin gene. In: Proceedings of the National Academy of Sciences of the United States of America. 1981 ; Vol. 78, No. 4 II. pp. 2455-2459.
@article{48b5cf9623ec447e9bf447f115c166dc,
title = "Base substitution in an intervening sequence of a β +-thalassemic human globin gene",
abstract = "β globin gene fragments from a patient with homozygous β +-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro transcription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the β +-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of β globin mRNA precursor molecules in β +-thalassemia.",
author = "Spritz, {R. A.} and P. Jagadeeswaran and Choudary, {Prabhakara V} and Biro, {P. A.} and Elder, {J. T.} and deRiel, {J. K.} and Manley, {J. L.} and Gefter, {M. L.} and Forget, {B. G.} and Weissman, {S. M.}",
year = "1981",
doi = "10.1073/pnas.78.4.2455",
language = "English (US)",
volume = "78",
pages = "2455--2459",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "4 II",

}

TY - JOUR

T1 - Base substitution in an intervening sequence of a β +-thalassemic human globin gene

AU - Spritz, R. A.

AU - Jagadeeswaran, P.

AU - Choudary, Prabhakara V

AU - Biro, P. A.

AU - Elder, J. T.

AU - deRiel, J. K.

AU - Manley, J. L.

AU - Gefter, M. L.

AU - Forget, B. G.

AU - Weissman, S. M.

PY - 1981

Y1 - 1981

N2 - β globin gene fragments from a patient with homozygous β +-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro transcription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the β +-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of β globin mRNA precursor molecules in β +-thalassemia.

AB - β globin gene fragments from a patient with homozygous β +-thalassemia have been cloned and subjected to restriction endonuclease, nucleotide sequence, and in vitro transcription analyses. Restriction endonuclease mapping of the cloned gene fragments revealed no deletions or other rearrangements, and transcription of the thalassemic gene appeared to be normal in vitro. However, nucleotide sequence analysis of the β +-thalassemic gene fragments permitted identification of a single base change in the body of the small intervening sequence. This nucleotide change creates a sequence much like that of the 3' splice site of the small intervening sequence. The presence of a potential anomalous splicing site as a result of this base change suggests a mechanism for defective posttranscriptional processing of β globin mRNA precursor molecules in β +-thalassemia.

UR - http://www.scopus.com/inward/record.url?scp=0005188076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0005188076&partnerID=8YFLogxK

U2 - 10.1073/pnas.78.4.2455

DO - 10.1073/pnas.78.4.2455

M3 - Article

C2 - 6264477

AN - SCOPUS:0005188076

VL - 78

SP - 2455

EP - 2459

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 4 II

ER -