A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia

J. M. Gonzalez-Redondo, T. A. Stoming, A. Kutlar, F. Kutlar, K. D. Lanclos, E. F. Howard, Y. J. Fei, M. Aksoy, C. Altay, A. Gurgey, A. N. Basak, G. D. Efremov, G. Petkov, T. H.J. Huisman

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C→T mutation at nucleotide position -101 relative to the Cap site of the β-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 β-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the -101 C→T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of β-thalassemia. It is relatively rare because it was absent among several hundred normal and β-thalassemia chromosomes.

Original languageEnglish (US)
Pages (from-to)1705-1711
Number of pages7
JournalBlood
Volume73
Issue number6
StatePublished - Jan 1 1989

Fingerprint

Thalassemia
Globins
Conserved Sequence
DNA sequences
Hemoglobin A2
Chromosomes
Genetic Promoter Regions
Substitution reactions
Nucleotides
Genes
Mutation
Chloramphenicol O-Acetyltransferase
Oligonucleotide Probes
Transcription
beta-Thalassemia
Sequence Analysis

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Gonzalez-Redondo, J. M., Stoming, T. A., Kutlar, A., Kutlar, F., Lanclos, K. D., Howard, E. F., ... Huisman, T. H. J. (1989). A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia. Blood, 73(6), 1705-1711.

A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia. / Gonzalez-Redondo, J. M.; Stoming, T. A.; Kutlar, A.; Kutlar, F.; Lanclos, K. D.; Howard, E. F.; Fei, Y. J.; Aksoy, M.; Altay, C.; Gurgey, A.; Basak, A. N.; Efremov, G. D.; Petkov, G.; Huisman, T. H.J.

In: Blood, Vol. 73, No. 6, 01.01.1989, p. 1705-1711.

Research output: Contribution to journalArticle

Gonzalez-Redondo, JM, Stoming, TA, Kutlar, A, Kutlar, F, Lanclos, KD, Howard, EF, Fei, YJ, Aksoy, M, Altay, C, Gurgey, A, Basak, AN, Efremov, GD, Petkov, G & Huisman, THJ 1989, 'A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia', Blood, vol. 73, no. 6, pp. 1705-1711.
Gonzalez-Redondo, J. M. ; Stoming, T. A. ; Kutlar, A. ; Kutlar, F. ; Lanclos, K. D. ; Howard, E. F. ; Fei, Y. J. ; Aksoy, M. ; Altay, C. ; Gurgey, A. ; Basak, A. N. ; Efremov, G. D. ; Petkov, G. ; Huisman, T. H.J. / A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia. In: Blood. 1989 ; Vol. 73, No. 6. pp. 1705-1711.
@article{47f86d348e324efdb3f54ecfb95e326d,
title = "A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia",
abstract = "Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C→T mutation at nucleotide position -101 relative to the Cap site of the β-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 β-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the -101 C→T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of β-thalassemia. It is relatively rare because it was absent among several hundred normal and β-thalassemia chromosomes.",
author = "Gonzalez-Redondo, {J. M.} and Stoming, {T. A.} and A. Kutlar and F. Kutlar and Lanclos, {K. D.} and Howard, {E. F.} and Fei, {Y. J.} and M. Aksoy and C. Altay and A. Gurgey and Basak, {A. N.} and Efremov, {G. D.} and G. Petkov and Huisman, {T. H.J.}",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "73",
pages = "1705--1711",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia

AU - Gonzalez-Redondo, J. M.

AU - Stoming, T. A.

AU - Kutlar, A.

AU - Kutlar, F.

AU - Lanclos, K. D.

AU - Howard, E. F.

AU - Fei, Y. J.

AU - Aksoy, M.

AU - Altay, C.

AU - Gurgey, A.

AU - Basak, A. N.

AU - Efremov, G. D.

AU - Petkov, G.

AU - Huisman, T. H.J.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C→T mutation at nucleotide position -101 relative to the Cap site of the β-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 β-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the -101 C→T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of β-thalassemia. It is relatively rare because it was absent among several hundred normal and β-thalassemia chromosomes.

AB - Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C→T mutation at nucleotide position -101 relative to the Cap site of the β-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 β-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the -101 C→T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of β-thalassemia. It is relatively rare because it was absent among several hundred normal and β-thalassemia chromosomes.

UR - http://www.scopus.com/inward/record.url?scp=0024477306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024477306&partnerID=8YFLogxK

M3 - Article

C2 - 2713503

AN - SCOPUS:0024477306

VL - 73

SP - 1705

EP - 1711

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -