11 results on '"Redondo JM"'
Search Results
2. A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia.
- Author
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Gonzalez-Redondo JM, Stoming TA, Kutlar A, Kutlar F, Lanclos KD, Howard EF, Fei YJ, Aksoy M, Altay C, and Gurgey A
- Subjects
- Base Sequence, Cloning, Molecular, Gene Expression Regulation, Heterozygote, Humans, Molecular Sequence Data, Mutation, RNA, Messenger genetics, Transcription, Genetic, Globins genetics, Promoter Regions, Genetic, Thalassemia genetics
- 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 beta-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 beta-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 beta-thalassemia. It is relatively rare because it was absent among several hundred normal and beta-thalassemia chromosomes.
- Published
- 1989
3. Nucleotide sequence of the human theta 1-globin gene.
- Author
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Gonzalez-Redondo JM, Han IS, Gu YC, and Huisman TH
- Subjects
- Amino Acid Sequence, Base Sequence, Cloning, Molecular, Female, Humans, Leukocytes metabolism, Molecular Sequence Data, Nucleic Acid Hybridization, Genes, Globins genetics
- Abstract
We have cloned and sequenced the human theta 1-globin gene. The nucleotide sequence and organization of the human theta 1 gene (exons, introns, promoter, and polyadenylation signals) are similar to those reported for the orangutan theta 1-globin gene. If these genes are functional, the sequences of their theta 1-globin chains would differ by only one amino acid residue (at position 137).
- Published
- 1988
- Full Text
- View/download PDF
4. Abnormal processing of beta-Malay globin RNA.
- Author
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Gonzalez-Redondo JM, Brickner HE, and Atweh GF
- Subjects
- Base Sequence, Gene Amplification, HeLa Cells, Humans, In Vitro Techniques, RNA, Messenger genetics, Transfection, Globins genetics, Hemoglobins, Abnormal genetics, RNA Processing, Post-Transcriptional, Thalassemia genetics
- Abstract
Hemoglobin Malay (alpha 2 beta 2 19 Asn----Ser) has been observed in a few Malaysian patients with thalassemia intermedia. The beta Malay substitution increases the homology of the cryptic splice site at codons 17/18/19 of the beta-globin gene to the donor consensus splice sequence, suggesting that the beta-thalassemia associated with this mutation may be due to the generation of a new splice site. To test this hypothesis, we constructed a hybrid gene where we replaced part of a normal beta-globin gene with a PCR amplified region of the beta Malay gene. The expression of this mutant gene was studied in a heterologous transient expression system. The data show that nearly 25% of globin mRNA produced by this gene is abnormally spliced at the new splice site, providing a molecular mechanism for the beta-thalassemia associated with the mutation.
- Published
- 1989
- Full Text
- View/download PDF
5. Hb S(C)-beta+-thalassaemia: different mutations are associated with different levels of normal Hb A.
- Author
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Gonzalez-Redondo JM, Kutlar F, Kutlar A, Stoming TA, de Pablos JM, Kilinç Y, and Huisman TH
- Subjects
- Adolescent, Child, Child, Preschool, DNA Probes, Fetal Hemoglobin analysis, Haplotypes, Hemoglobin C genetics, Hemoglobin, Sickle genetics, Humans, Thalassemia blood, Globins genetics, Hemoglobin A analysis, Mutation, Thalassemia genetics
- Abstract
Analysis of amplified DNA through hybridization with 32P-labelled synthetic oligonucleotide probes has provided data about the molecular abnormality for beta-thalassaemic globin genes present in 32 Black and eight Mediterranean patients with Hb S(C)-beta+-thalassaemia. The patients were categorized according to these beta-thalassaemia mutations, and average haematological and haemoglobin composition data were compared for each of four different groups. Twenty-eight Black patients had the -29 A----G substitution and four had the -88 C----T substitution; all had mild disease with comparable haematology and an average Hb A level of 20%. Six Mediterranean patients had the IVS-1, 110 G----A mutation; their haematological data were nearly the same as that for the Black patients except for a lower Hb A value of 11%. Two Turkish patients with the IVS-2, 745 C----G mutation were more severely affected with mild sickling disease and low Hb A levels of 5%. Hb F levels varied greatly because of age differences; high G gamma values were observed only in patients with a beta-thalassaemia chromosome having an Xmn I site 5' to G gamma. The data readily explain the variability in Hb A level that has been repeatedly noted in patients with Hb S(C)-beta+-thalassaemia.
- Published
- 1988
- Full Text
- View/download PDF
6. Beta-thalassemia due to a T----A mutation within the ATA box.
- Author
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Fei YJ, Stoming TA, Efremov GD, Efremov DG, Battacharia R, Gonzalez-Redondo JM, Altay C, Gurgey A, and Huisman TH
- Subjects
- Base Sequence, Humans, Mutation, Transcription, Genetic, Globins genetics, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Thalassemia genetics
- Abstract
Sequence analyses of amplified DNA from a Yugoslavian patient with Hb Lepore-beta-thalassemia and from his father with a simple beta-thalassemia trait have revealed a T----A mutation within the ATA box at a position 30 base pairs upstream from the Cap site. The nucleotide substitution was confirmed through dot-blot analysis of amplified DNA with specific 32P-labeled synthetic oligonucleotide probes. The patient had a clinically severe condition; his Hb Lepore-beta-thalassemia was of the beta + type, as about 8-10% of the non-alpha chain was normal beta A. The same T----A mutation at nucleotide -30 was present on both chromosomes of a young Turkish patient who suffered from a thalassemia intermedia with a low level of Hb F (13.1%) and a relatively high beta A chain synthesis. These data are similar to those obtained for other types of beta +-thalassemia caused by comparable substitutions at positions 31, 29, and 28 base pairs upstream from the Cap site of the beta-globin gene.
- Published
- 1988
- Full Text
- View/download PDF
7. Frameshift codon 5 [Fsc-5 (-CT)] thalassemia; a novel mutation detected in a Greek patient.
- Author
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Kollia P, Gonzalez-Redondo JM, Stoming TA, Loukopoulos D, Politis C, and Huisman TH
- Subjects
- Adolescent, Base Sequence, Codon, DNA Mutational Analysis, Humans, Male, Molecular Sequence Data, Peptide Chain Termination, Translational, Globins genetics, Thalassemia genetics
- Abstract
Sequence analysis and dot-blot hybridization of DNA from a Greek patient with a transfusion dependent thalassemia revealed the combination of a beta IVS-I-1 G----A mutation (beta(0) -thalassemia) and a hitherto undescribed frameshift mutation; the latter concerns the absence of a CT dinucleotide from codon 5 and results in a termination signal at the new codon 21 (also a beta (0)-thalassemia).
- Published
- 1989
- Full Text
- View/download PDF
8. Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major.
- Author
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Yang KG, Kutlar F, George E, Wilson JB, Kutlar A, Stoming TA, Gonzalez-Redondo JM, and Huisman TH
- Subjects
- Amino Acid Sequence, Base Sequence, Codon, Humans, Malaysia, Mutation, Thalassemia ethnology, Genes, Globins genetics, Hemoglobin E genetics, Hemoglobins, Abnormal genetics, Thalassemia genetics
- Abstract
This study concerned the identification of the beta-thalassaemia mutations that were present in 27 Malay patients with Hb E-beta-thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all beta-thalassaemia chromosomes carried the G----C substitution at nucleotide 5 of IVS-I; the commonly occurring Chinese anomalies such as the frameshift at codons 41 and 42, the nonsense mutation A----T at codon 17, the A----G substitution at position -28 of the promoter region, and the C----T substitution at position 654 of the second intron, were rare or absent. Two new thalassaemia mutations were discovered. The first involves a frameshift at codon 35 (-C) that was found in two patients with Hb E-beta zero-thalassaemia and causes a beta zero-thalassaemia because a stop codon is present at codon 60. The second is an AAC----AGC mutation in codon 19 that was present on six chromosomes. This substitution results in the production of an abnormal beta chain (beta-Malay) that has an Asn----Ser substitution at position beta 19. Hb Malay is a 'Hb Knossos-like' beta +-thalassaemia abnormality; the A----G mutation at codon 19 likely creates an alternate splicing site between codons 17 and 18, reducing the efficiency of the normal donor splice site at IVS-I to about 60%.
- Published
- 1989
- Full Text
- View/download PDF
9. Characterization of three types of beta zero-thalassemia resulting from a partial deletion of the beta-globin gene.
- Author
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Gonzalez-Redondo JM, Kattamis C, and Huisman TH
- Subjects
- Base Sequence, Black People genetics, Chromosome Mapping, Cloning, Molecular, Deoxyribonuclease BamHI, Deoxyribonuclease EcoRI, Deoxyribonuclease HindIII, Exons, Female, Gene Amplification, Greece ethnology, Heterozygote, Humans, Introns, Middle Aged, Molecular Sequence Data, Nucleic Acid Hybridization, Turkey ethnology, Chromosome Deletion, Globins genetics, Thalassemia genetics
- Abstract
Three patients heterozygous for a partial deletion of the beta-globin gene were studied: an American Black with an approximately 1.35 kb deletion, a Turkish patient with an approximately 300 nucleotide deletion, and a Greek patient with a newly discovered deletion of 44 nucleotides. The DNA was amplified by the polymerase chain reaction procedure and sequenced; only the DNA with the deletion was amplified for the patients with the approximately 1.35 kb and approximately 300 bp deletion, facilitating the interpretation of the sequencing gels. The amplified DNA fragments from these two chromosomes were also cloned into a plasmid vector and sequenced. The size of the deletion found in the Turkish patient is 290 nucleotides and includes 123, 124 or 125 nucleotides 5' to the Cap site, the 5' untranslated region, exon 1, and 25, 24, or 23 nucleotides of the first intron. The total size of the deletion of the Black patient is 1393 nucleotides including 485 (484) bp 5' to the Cap site, exon 1, intron 1, exon 2, and 413 (414) nucleotides of the second intron. The new deletion in the Greek beta-thalassemic patient was detected by direct sequencing of amplified DNA; the 44 bp deletion begins within codon 24 or between codons 24 and 25, and includes the first 26 or 27 nucleotides of intron 1. This deletion was confirmed by hybridization of amplified DNA with a specific oligonucleotide probe and by sequence analysis of amplified DNA cloned in a plasmid. A 7 bp homology sequence (GACAGGT) was found at both sides of the 290 bp deletion, while only 3 nucleotides were repeated at both sides of the 44 nucleotide deletion (GGT). No homology was found between the breakpoints of the 1393 nucleotide deletion.
- Published
- 1989
- Full Text
- View/download PDF
10. Characterization of a newly discovered alpha-thalassaemia-1 in two Spanish patients with Hb H disease.
- Author
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Gonzalez-Redondo JM, Diaz-Chico JC, Malcorra-Azpiazu JJ, Balda-Aguirre MI, and Huisman TH
- Subjects
- Adolescent, Adult, Child, Chromosome Deletion, Chromosome Mapping, Chromosomes, Human, Pair 16, DNA Probes, Female, Humans, Male, Middle Aged, Globins genetics, Thalassemia genetics
- Abstract
A new deletion of more than 27 kb, removing the psi zeta 1, psi alpha 2, psi alpha 1, alpha 2, alpha 1 and theta 1 globin genes has been found in four members of a Spanish family, including two patients with Hb H disease. The 5' end point of the deletion is located between the zeta and psi zeta genes, and the 3' end of the deletion is downstream of the 3' hypervariable region.
- Published
- 1988
- Full Text
- View/download PDF
11. Characterization of a new alpha-thalassemia-1 deletion in a Spanish family.
- Author
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Gonzalez-Redondo JM, Gilsanz F, and Ricard P
- Subjects
- Adult, Chromosome Deletion, DNA Restriction Enzymes genetics, Female, Hematologic Tests, Hemoglobin A analysis, Hemoglobin A2 analysis, Humans, Restriction Mapping, Spain, Globins genetics, Thalassemia genetics
- Abstract
A new type of alpha-thalassemia-1 was characterized in one Spanish patient with Hb H disease and in her mother. The restriction map of this deletion suggests that the deletion of 22 kb has occurred on a chromosome carrying a zeta-globin triplication. The resulting chromosome lacks the alpha 2- and alpha 1-globin genes, the psi alpha 2- and psi alpha 1-globin genes, and one of the three zeta-globin genes, while the other two zeta-globin genes and the theta 1-globin gene have been retained.
- Published
- 1989
- Full Text
- View/download PDF
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