共查询到20条相似文献,搜索用时 15 毫秒
1.
E I Shvarts A A Gol'tsov O K Kaboev I N Bakhlanova A N Alekseev 《Bioorganicheskaia khimiia》1989,15(4):556-559
A mutation causing beta 0-thalassaemia in Azerbaijanian population is shown, by the polymerase chain reaction followed by Maxam-Gilbert sequencing, to be the deletion of dinucleotide AA from the eight codone of beta-globin gene (the mutation is known to exist also in Turkey and Lebanon). Two other mutations have also been found in beta-globin gene of the same DNA, one of which (transversion C----G at position 16 of intron 2) eliminates the polymorphic AvaII-site and is associated with thalassaemia, and other is transition C----T in the third position of the second beta-globin codon. 相似文献
2.
G Fucharoen S Fucharoen A Jetsrisuparb Y Fukumaki 《Biochemical and biophysical research communications》1990,170(2):698-704
Amplification of DNA via polymerase chain reaction directly from a small amount of a buffy coat fraction was used to study the molecular basis of HbE-beta-thalassemia in the northeastern Thai population. Eight different mutations including the new one causing a beta o-thalassemia phenotype were detected. This novel mutation is an amber mutation at codon 26, which occurs at the same position as that of HbE; the most common hemoglobin variant in Southeast Asian countries. A pitfall in detection of the HbE mutation by restriction enzyme analysis was pointed out and differential diagnosis of the HbE mutation and the novel one by using allele specific oligonucleotide probes were described. Analysis of polymorphic restriction sites in the beta-globin gene cluster containing the beta E gene revealed two previously undescribed haplotypes in the Southeast Asian populations, which provide evidence for the multiple origins of beta E gene in Southeast Asian populations. 相似文献
3.
Jamsai D Zaibak F Khongnium W Vadolas J Voullaire L Fowler KJ Gazeas S Fucharoen S Williamson R Ioannou PA 《Genomics》2005,85(4):453-461
Accurate animal models that recapitulate the phenotype and genotype of patients with beta-thalassemia would enable the development of a range of possible therapeutic approaches. Here we report the generation of a mouse model carrying the codons 41-42 (-TTCT) beta-thalassemia mutation in the intact human beta-globin locus. This mutation accounts for approximately 40% of beta-thalassemia mutations in southern China and Thailand. We demonstrate a low level of production of gamma-globins from the mutant locus in day 18 embryos, as well as production of mutant human beta-globin mRNA. However, in contrast to transgenic mice carrying the normal human beta-globin locus, 4-bp deletion mice fail to show any phenotypic complementation of the knockout mutation of both murine beta-globin genes. Our studies suggest that this is a valuable model for gene correction in hemopoietic stem cells and for studying the effects of HbF inducers in vivo in a "humanized" thalassemic environment. 相似文献
4.
Duplication followed by deletion accounts for the structure of an Indian deletion beta (0)-thalassemia gene. 总被引:10,自引:4,他引:10 下载免费PDF全文
Nucleotide sequence analysis of a cloned deletion beta-globin gene from a patient with beta(0)-thalassemia demonstrates a 619 nucleotide deletion extending from the 3' third of the second intervening sequence through 209 bases of 3' flanking DNA. However, an additional novel heptanucleotide was identified between the deletion endpoints, suggesting a complex etiology for this rearrangement. 相似文献
5.
A A Gol'tsov V L Surin A V Luk'ianenko A A Alekseev O K Kaboev S V Vinogradov G Ia Solov'ev Iu A Berlin E I Shvarts 《Bioorganicheskaia khimiia》1989,15(7):1001-1002
Molecular nature of two beta 0-thalassaemia-causing mutations in beta-globin gene in Azerbaijanian population has been elucidated, viz., C-T transition in 39 codon (nonsense mutation) and previously unknown G deletion in 82/83 codons. 相似文献
6.
Schachter H 《Biochimica et biophysica acta》1999,1455(2-3):61-62
7.
Juan P. Bustamante Alessandra Bonamore Alejandro D. Nadra Natascia Sciamanna Alberto Boffi Darío A. Estrin Leonardo Boechi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures.Methods
We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position.Results
The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible.Conclusions
This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability.General significance
These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins. 相似文献8.
9.
10.
11.
Molecular basis of mitochondrial DNA disease 总被引:8,自引:0,他引:8
Mitochondrial ATP production via oxidative phosphorylation (OXPHOS) is essential for normal function and maintenance of human organ systems. Since OXPHOS biogenesis depends on both nuclear- and mitochondrial-encoded gene products, mutations in both genomes can result in impaired electron transport and ATP synthesis, thus causing tissue dysfunction and, ultimately, human disease. Over 30 mitochondrial DNA (mtDNA) point mutations and over 100mtDNA rearrangements have now been identified as etiological factors in human disease. Because of the unique characteristics of mtDNA genetics, genotype/phenotype associations are often complex and disease expression can be influenced by a number of factors, including the presence of nuclear modifying or susceptibility alleles. Accordingly, these mutations result in an extraordinarily broad spectrum of clinical phenotypes ranging from systemic, lethal pediatric disease to late-onset, tissue-specific neurodegenerative disorders. In spite of its complexity, an understanding of the molecular basis of mitochondrial DNA disease will be essential as the first step toward rationale and permanent curative therapy. 相似文献
12.
13.
H. Harris 《BMJ (Clinical research ed.)》1968,2(5598):135-141
14.
Naka I Ohashi J Nuchnoi P Hananantachai H Looareesuwan S Tokunaga K Patarapotikul J 《Biochemical genetics》2008,46(11-12):708-711
Hemoglobin E (HbE; beta26Glu --> Lys) is the most common variant of the beta-globin gene in Southeast Asia; it has been suggested that it confers resistance against Plasmodium falciparum malaria. In this study 306 adult patients with P. falciparum malaria (198 mild and 108 cerebral malaria patients) living in northwest Thailand were investigated to examine whether the HbE variant is associated with protection from cerebral malaria. Our results revealed that the sample allele frequency of HbE was not significantly different between mild (7.3%) and cerebral malaria (7.4%) patients. Thus, the HbA/HbE polymorphism would not be a major genetic factor influencing the onset of cerebral malaria in Thailand. 相似文献
15.
16.
The beta-globin gene in Sardinian delta beta 0-thalassemia carries a C----T nonsense mutation at codon 39. 总被引:2,自引:1,他引:2 下载免费PDF全文
Sardinian delta beta 0-thalassemia is an inherited syndrome characterized by the inactivity of the beta-globin gene and the persistent activity of the fetal gamma-globin genes, particularly the A gamma-globin gene. Previous mapping studies with restriction enzymes failed to show any abnormality in the non-alpha globin gene cluster. We have now examined the possibility that this syndrome might result from a single rather than two different defects. Restriction enzyme polymorphisms linked to the delta beta 0-thalassemic non-alpha globin fragments were defined providing the basis for cloning the delta beta 0-thalassemic beta-globin gene from the DNA of a heterozygous patient. This gene appears to carry a C----T single mutation causing the appearance of a stop codon at amino acid position 39 of the beta-globin gene. This mutation was previously reported in beta 0-thalassemic patients, in linkage with different haplotypes. We conclude that Sardinian delta beta 0-thalassemia is the result of two separate mutations, the former one (unknown) responsible for persistent expression of gamma-globin genes, the latter for beta 0-thalassemia. 相似文献
17.
Gene analysis in delta beta and delta (0) thalassemia 总被引:1,自引:0,他引:1
M Baird M C Driscoll I Ben-Bassat Y Ohta F Nakamura A Bloom A Bank 《The Journal of biological chemistry》1984,259(1):512-515
18.
Mitrousis G Olia AS Walker-Kopp N Cingolani G 《The Journal of biological chemistry》2008,283(12):7877-7884
The nuclear import of uridine-rich ribonucleoproteins is mediated by the transport adaptor snurportin 1 (SNP1). Similar to importin alpha, SNP1 uses an N-terminal importin beta binding (sIBB) domain to recruit the receptor importin beta and gain access to the nucleus. In this study, we demonstrate that the sIBB domain has a bipartite nature, which contains two distinct binding determinants for importin beta. The first determinant spans residues 25-65 and includes the previously identified importin alpha IBB (alphaIBB) region of homology. The second binding determinant encompasses residues 1-24 and resembles region 1011-1035 of the nucleoporin 153 (Nup153). The two binding determinants synergize within the sIBB domain to confer a low nanomolar binding affinity for importin beta (K(d) approximately 2 nm) in an interaction that, in vitro, is displaced by RanGTP. We propose that in vivo the synergy of Nup153 and nuclear RanGTP promotes translocation of uridine-rich ribonucleoproteins into the nucleus. 相似文献
19.
20.
Amaya Leunda Bernadette Van Vaerenbergh Aline Baldo Stefan Roels Philippe Herman 《朊病毒》2013,7(5):420-424
Shadoo (Sho) is a brain glycoprotein with similarities to the unstructured region of PrPC. Frameshift alleles of the Sho gene, Sprn, are reported in variant Creutzfeldt-Jakob disease (vCJD) patients while Sprn mRNA knockdown in PrP-null (Prnp0/0) embryos produces lethality, advancing Sho as the hypothetical PrP-like “pi” protein. Also, Sho levels are reduced as misfolded PrP accumulates during prion infections. To penetrate these issues we created Sprn null alleles (Daude et al., Proc. Natl. Acad. Sci USA 2012; 109(23): 9035–40). Results from the challenge of Sprn null and TgSprn transgenic mice with rodent-adapted prions coalesce to define downregulation of Sho as a “tracer” for the formation of misfolded PrP. However, classical BSE and rodent-adapted BSE isolates may behave differently, as they do for other facets of the pathogenic process, and this intriguing variation warrants closer scrutiny. With regards to physiological function, double knockout mice (Sprn0/0/Prnp0/0) mice survived to over 600 d of age. This suggests that Sho is not pi, or, given the accumulating data for many activities for PrPC, that the pi hypothesis invoking a discrete signaling pathway to maintain neuronal viability is no longer tenable. 相似文献