Using the dominant control region (DCR) sequences that flank the beta-globin gene locus, we have been able to achieve high-level expression of the human alpha-globin gene in transgenic mice. Expression in fetal liver and blood is copy number dependent and at levels comparable to that of the endogenous mouse alpha-globin genes. Transgenic fetuses with high-copy numbers of the transgene suffer severe anemia and die before birth. Using a construct with both the human alpha- and beta-globin genes and the beta-globin DCR, live mice with low-copy numbers were obtained. Both human globin genes are expressed at high levels in adult red cells to give human hemoglobin HbA in amounts equal to or greater than endogenous mouse hemoglobin. Expression of HbA in murine red cells is not accompanied by any increase in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC). However, these transgenic mice tend to have an increased number of reticulocytes in peripheral blood; consistent with some
Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.
Adult White Leghorn chickens were rendered anemic by injection with 1-acetyl-2-phenylhydrazine and then treated with parenteral 5-azacytidine, and levels of embryonic globin RNA in circulating reticulocytes were measured. A very small but detectable amount of correctly initiated embryonic p-type globin RNA was detected in reticulocytes from birds treated with 5-azacytidine, while none was detected in reticulocytes from those receiving only phenylhydrazine or phenylhydrazine plus 1-beta-D-arabinofuranosylcytosine (cytosine arabinonucleoside). An attempt to increase embryonic globin RNA induction by treatment with parenteral sodium butyrate after 7 days of 5-azacytidine administration resulted in a 5- to 10-fold increase in the level of embryonic globin RNA. However, sodium butyrate did not induce embryonic gene expression when given alone or after treatment with cytosine arabinonucleoside. Sodium butyrate treatment also caused a DNase I-hypersensitive site to be exposed at the 5 end of the ...
We have studied the interaction of the alpha alpha alpha/alpha alpha gene arrangement with various beta globin genotypes (AA, AS, AC, SS and SC). Whereas this interaction has no detectable clinical or haematological effects in subjects with AA, SS or SC genotypes it is associated with a significantly increased level of Hb S or Hb C in heterozygotes for these variants. These findings indicate that the additional alpha globin gene in the alpha alpha alpha gene arrangement is functional.
Abstract Human β-globin disorders are relatively common genetic diseases cause by mutations in the β-globin gene. Increasing the expression of the γ-globin gene has great benefits in reducing complications associated with these diseases. The Oct-1 transcription factor is involved in the transcriptional regulation of the γ-globin gene. The human γ-globin genes (both Aγ and Gγ-globin genes) carry three Oct-1 transcription factor consensus sequences within their promoter regions. We have studied the possibility of inducing γ-globin gene expression using decoy oligonucleotides that target the Oct-1 transcription factor consensus sequence. A double-stranded 22 bp decoy oligonucleotide containing the Oct-1 consensus sequence was synthesized. The results obtained from our in vitro binding assay revealed a strong competitive binding of the decoy oligonucleotide for the Oct-1 transcription factor. When K562 human erythroleukemia cells were treated with the Oct-1 decoy oligonucleotide, significant
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myoglobin and hemoglobin. Both of these proteins reversibly bind oxygen via a heme prosthetic group. They are widely distributed in many organisms. Globin superfamily members share a common three-dimensional fold. This globin fold typically consists of eight alpha helices, although some proteins have additional helix extensions at their termini. Since the globin fold contains only helices, it is classified as an all-alpha protein fold. The globin fold is found in its namesake globin families as well as in phycocyanins. The globin fold was thus the first protein fold discovered (myoglobin was the first protein whose structure was solved). The eight helices of the globin fold core share significant nonlocal structure, unlike other structural motifs in which amino ...
951 1234 DNase hypersensitive site 4 4550 4775 DNase hypersensitive site 3 8486 8860 DNase hypersensitive site 2 12752 13769 DNase hypersensitive site 1 116 431 Right Alu 1968 2258 Left Alu 5605 5918 Right Alu 8019 8314 Right Alu 10612 10924 Right Alu 12912 13066 Left L1 14836 15071 Right L1 16918 17218 Left Alu 17940 18231 Right Alu 19486 21080 epsilon-globin gene 19486 19632 Exon 1 19755 19977 Exon 2 20833 21080 Exon 3 23118 31136 Left L1 25885 27987 Left InnerL1 32407 32711 Right Alu 32986 33101 Left L1 34478 36069 G-gamma-globin gene 34478 34622 Exon 1 34745 34967 Exon 2 35854 36069 Exon 3 37921 38039 Left L1 39414 40985 A-gamma-globin gene 39414 39558 Exon 1 39681 39903 Exon 2 40770 40985 Exon 3 42695 43274 Left L1 44788 45108 Right Alu 45658 47272 eta-globin pseudo gene 45658 45800 Exon 1 45922 46144 Exon 2 46997 47272 Exon 3 50895 51198 Left Alu 51976 52276 Right Alu 53222 53540 Left L1 54740 56389 delta-globin gene 54740 54881 Exon 1 55010 55232 Exon 2 56131 56389 Exon 3 62137 63742 ...
Hemoglobin subunit epsilon is a protein that in humans is encoded by the HBE1 gene. The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5 - epsilon - gamma-G - gamma-A - delta - beta - 3. Hemoglobin Human β-globin locus GRCh38: Ensembl release 89: ENSG00000213931 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000052217 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Higgs DR, Vickers MA, Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (May 1989). "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. ...
TY - JOUR. T1 - Neuroglobin, a novel member of the globin family, is expressed in focal regions of the brain. AU - Mammen, Pradeep P A. AU - Shelton, John M.. AU - Goetsch, Sean C.. AU - Williams, S. Clay. AU - Richardson, James A.. AU - Garry, Mary G.. AU - Garry, Daniel J.. PY - 2002/12/1. Y1 - 2002/12/1. N2 - Hemoproteins are widely distributed among unicellular eukaryotes, plants, and animals. In addition to myoglobin and hemoglobin, a third hemoprotein, neuroglobin, has recently been isolated from vertebrate brain. Although the functional role of this novel member of the globin family remains unclear, neuroglobin contains a heme-binding domain and may participate in diverse processes such as oxygen transport, oxygen storage, nitric oxide detoxification, or modulation of terminal oxidase activity. In this study we utilized in situ hybridization (ISH) and RT-PCR analyses to examine the expression of neuroglobin in the normoxic and hypoxic murine brain. In the normoxic adult mouse, neuroglobin ...
A common mutation causing thalassemia in Mediterranean populations is an amber (UAG) nonsense mutation at the 39th codon of the human β globin gene, the β-39 mutation. Studies of mRNA metabolism in reticulocytes from patients with β-39 thalassemia and studies using heterologous transfection systems have suggested the possibility that this mutation affects not only protein synthesis but also alters mRNA metabolism. This phenomenon has been investigated further by two approaches. A careful series of RNA expression studies were performed comparing expression of β-39 to β-normal (β-nl). These experiments led to the conclusion that the defect in expression of the β-39 mRNA resides in the nucleus. A number of nonsense and missense mutations of the β globin gene were constructed by oligonucleotide-directed site-specific mutagenesis. Their expression was studied in a heterologous transfection system. These studies strongly suggest that the presence of a nonsense mutation (but not a missense mutation) in
Recent evidence suggests that long-range enhancers and gene promoters are in close proximity, which might reflect the formation of chromatin loops. Here, we examined the mechanism for DNA looping at the beta-globin locus. By using chromosome conformation capture (3C), we show that the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 are required for the physical interaction between the beta-globin locus control region (LCR) and the beta-major globin promoter. Kinetic studies reveal that GATA-1-induced loop formation correlates with the onset of beta-globin transcription and occurs independently of new protein synthesis. GATA-1 occupies the beta-major globin promoter normally in fetal liver erythroblasts from mice lacking the LCR, suggesting that GATA-1 binding to the promoter and LCR are independent events that occur prior to loop formation. Together, these data demonstrate that GATA-1 and FOG-1 are essential anchors for a tissue-specific chromatin loop, providing general insights into
Highly purified RNase H (RNA·DNA hybrid ribonucleotidohydrolase, EC 3.1.4.34) from calf thymus was used to specifically remove the poly(A) sequences of purified rabbit globin mRNA after its hybridization with poly(dT). The deadenylylated globin mRNA was repurified by a one-step procedure including a nitrocellulose column. The poly(A) size and the content of unmodified mRNA were determined by hybridization with [(3)H]-poly(U), and it could be shown that the RNase H digestion method effectively removes this terminal poly(A) sequence. No difference in activity was found between mRNAs with and without poly(A) to initiate, elongate, terminate, and release newly synthesized globin chains in exogenous-mRNA-dependent, cell-free, protein-synthesizing systems from wheat embryo, ascites Krebs II cells, and rat liver. Furthermore, poly(A)-free globin mRNA competed with the same efficiency as authentic globin mRNA against chick ovalbumin mRNA when translated under total mRNA saturation conditions. It is ...
TY - JOUR. T1 - An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis. AU - Yu, Xiang. AU - Kong, Yi. AU - Dore, Louis C.. AU - Abdulmalik, Osheiza. AU - Katein, Anne M.. AU - Zhou, Suiping. AU - Choi, John K.. AU - Gell, David. AU - Mackay, Joel P.. AU - Gow, Andrew J.. AU - Weiss, Mitchell J.. PY - 2007/7/2. Y1 - 2007/7/2. N2 - Erythrocyte precursors produce abundant α- and β-globin proteins, which assemble with each other to form hemoglobin A (HbA), the major blood oxygen carrier. αHb-stabilizing protein (AHSP) binds free α subunits reversibly to maintain their structure and limit their ability to generate reactive oxygen species. Accordingly, loss of AHSP aggravates the toxicity of excessive free α-globin caused by β-globin gene disruption in mice. Surprisingly, we found that AHSP also has important functions when free α-globin is limited. Thus, compound mutants lacking both Ahsp and 1 of 4 α-globin genes (genotype Ahsp-/-α-globin -/-α/αα) ...
[Molecular mechanisms of globin gene regulation and disregulation].: Human globin genes are expressed in tissue and developmental stage specific manners. Variou
TY - JOUR. T1 - Characterization of an unique RNA initiated immediately upstream from human α1 globin gene in vivo and in vitro. T2 - Polymerase II-dependence, tissue specificity, and subcellular location. AU - Hess, John. AU - Perez-Stable, Carlos. AU - Deisseroth, Al. AU - Shen, Che Kun James. PY - 1985/9/11. Y1 - 1985/9/11. N2 - We have identified an abundant transcript initiated upstream from the canonical cap site of human α1 globin gene in bone marrow cells and in COS-7 cells transfected with an α1 globin gene-containing plasmid. Similar to the major α1 globin transcript, this upstream RNA is present almost exclusively in the cytoplasm of the transfected COS-7 cells. It is also synthesized efficiently in vitro by RNA polymerase II in the nuclear extracts prepared from a Hela cell line and an erythroleukemia cell line, K562. RNAs isolated from these cell lines, however, do not contain this upstream transcript. The putative 5′ end of the α1 globin upstream RNA is mapped by primer ...
The KLF1 gene encodes a key transcription factor regulating the developmental switch from fetal to adult globin. Based on previous and recent experimental data it has been hypothesized that after birth high levels of KLF1 activate the HBB gene and BCL11A expression, which in turn suppresses HBG1/HBG2 expression, while in the fetus reduced KLF1 levels result in very low HBB and BCL11A gene expression and therefore in low beta and high gamma globin levels.6 It is interesting to note that subjects II-1 and II-2, with genetic compound for the two KLF1 mutations, have unbalanced alpha/beta globin chain synthesis ratio (i.e. in the beta-thalassemia carrier range), despite having normal beta globin gene sequence and not increased HbA2 levels. The reduced beta globin production and the excess of G-gamma chains partly resembles a late fetal or newborn condition, consistent with the key role of KLF1 in the globin switching. The milder imbalance in II-2 as compared to II-1 is due to the coinheritance of ...
Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γA and γG genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control γA methylation during development. DNA methylation causes a 20-fold repression of γA both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress γ gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and
Anthropogenetical Analysis of Abnormal Human -globin Gene Cluster Arrangement on Chromosome 16*. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ~22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (,1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the ...
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TY - JOUR. T1 - Hpal polymorphic site 3 of the human β-globin gene is inside a repetitive sequence and cannot be ascertained by polymerase chain reaction. AU - Wang, X.. AU - Bouhassira, Eric E.. PY - 1992. Y1 - 1992. KW - Haplotype. KW - Kpnl sequence. KW - PCR. UR - http://www.scopus.com/inward/record.url?scp=0026603960&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0026603960&partnerID=8YFLogxK. M3 - Article. VL - 39. SP - 226. EP - 227. JO - American Journal of Hematology. JF - American Journal of Hematology. SN - 0361-8609. IS - 3. ER - ...
Androglobin (Adgb) is a recently discovered globin type consisting of large chimeric proteins with an N-terminal calpain-like protease domain and a central globin domain. Adgb is predominantly expressed in testis tissue and the expression is associated with the post-meiotic stages of spermatogenesis. Although we knew that Adgb plays a crucial role in male fertility, its molecular function is still not clear. The aim of this thesis was clear: unraveling the molecular function of Adgb. This was approached by using different strategies: the function was studied on biochemical, cellular and biological level.. To perform an in vitro biochemical characterization of the globin domain of Adgb, the globin domain was recombinantly expressed in E.coli, P.pastoris and baculovirus infected insect cells. We encountered difficulties with the solubility of the globin domain and concluded that for a proper folding it requires the context of the full length Adgb protein. Hence, we expressed the full length Adgb ...
In the vascular wall, endothelial nitric oxide synthase (eNOS) produces NO to regulate peripheral vascular resistance, tissue perfusion, and blood pressure. In resistance arteries, eNOS couples with α-globin and, through chemical reactions, modulates NO diffusion needed for vascular smooth muscle relaxation. While α-globin protein alone is known to be unstable, the mechanisms that enable α-globin protein expression remain elusive. Here, Lechauve et al. report that arterial endothelium expresses α hemoglobin-stabilizing protein, which acts as a critical chaperone protein for α-globin expression and vascular function.. ...
We have constructed a minilocus that contains the 5 and 3 flanking regions of the human beta-globin locus and the beta-globin gene. These regions are characterized by erythroid-specific DNAase I-superhypersensitive sites and are normally located approximately 50 kb 5 and 20 kb 3 of the beta-gl …
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
GLOBINclear-Human Globin mRNA Removal Kit Depletes alpha and beta globin mRNA from blood total RNA with a simple magnetic bead procedure (no enzymatic treatments) Increases sensitivity of gene detection in microarray profiling experiments ,Unmask,Blood,RNA,for,Gene,Expression,Profiling,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
Takaras Human Beta-globin Control Primer Set contains a set of PCR primers that recognizes the human beta-globin gene at chromosome 11. Beta-globin makes up about half of the human hemoglobin tertrameric protein; in the normal human adult, the hemoglobin tetramer consists of two alpha chains and two beta chains. The Human Beta-globin Control Primer Set may be used as a experimental control during protocols such as PCR ...
The work in our laboratory focuses on analyzing the regulation of globin gene expression in red blood cells. The globin genes encode for components of hemoglobin. We use a combination of genetic and biochemical approaches to analyze the structure and function of the human b-globin locus control region (LCR), a powerful regulatory genetic element located far upstream of the globin genes. The LCR, which is composed of several sub-regions revealing high sensitivity to nucleases in erythroid cells enhances globin gene transcription in a developmental stage specific manner. We use transgenic mice, embryonic stem (ES) cell differentiation systems, and in vitro assays to elucidate the mechanism by which the LCR regulates the recruitment of transcription and chromatin modifying complexes to the b-globin gene locus.. ...
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The β‐globin constructs with the wild‐type ORF or with the nonsense codon at position 39 (NS 39) contain a genomic 1423 bp β‐globin gene fragment extending from the physiological translation initiation codon to the translation termination codon, which was inserted into the pCIneo vector (Promega) at the XhoI-XbaI sites of the polylinker. The wild‐type and NS 39 gene sequences were derived from a healthy proband and from a patient with homozygous β‐thalassaemia, respectively. Constructs cWT and cNS 39 were derived from RT-PCRs of cytoplasmic RNA from HeLa cells transfected with wild‐type and NS 39 constructs and were inserted into the same position of the pCIneo vector.. The cWT‐UTR and the cNS 39‐UTR series of constructs was generated by replacement of a fragment spanning from the EcoRI site in the nominal exon 3 to an XhoI site that was inserted by in vitro mutagenesis immediately 3′ of the termination codon by sequences extending from the same EcoRI site to the XhoI site ...
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Thalassemic syndromes are genetically determined disorders of hemoglobin synthesis with decreased production of either alpha or beta polypeptide chains of hemoglobin molecules. This reduced production results from markedly decreased amounts of globin messenger ribonucleic acid.
Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing. Alister P. W. Funnel, Ka Sin Mak, Natalie A. Twine, Gregory J. Pelka, Laura J. Norton, Tania Radziewic, Melinda Power, Marc R. Wilkins, Kim S. Bell-Anderson, Stuart T. Fraser, Andrew C. Perkins, Patrick P. Tam, Richard C. M. Pearson and Merlin Crossley. Mol Cel Biol. (2013) Aug; 33(15):2976-87. IF=4.2 Cit=15 (GS 18) ...
Preparations comprising, especially, globin that is insoluble at neutral pH, and therefore at physiological pH, in which the globin has been obtained from whole blood by depigmentation in a medium tha
The globin gene superfamily as a model system. A second area of research is geared towards understanding the role of gene duplication and whole-genome duplication in the evolution of key physiological innovations. Gene duplication is thought to play an extremely important role in the evolution of novel protein and pathway functions. However, there is still much debate about the specific evolutionary mechanisms that are responsible for the initial retention and subsequent functional divergence of duplicated genes. The globin gene superfamily is an ideal model system for investigating these issues because it is one of the most intensively studied multigene families from the standpoint of molecular genetics and phylogenetic history. The globin gene families also provide an excellent example of the kind of physiological versatility that can be attained through functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the same multimeric protein. For ...
Four polypeptide globin chains are arranged in pairs forming the tetrameric molecule or globin portion of hemoglobin. Each globin chain is covalently attached to a heme moiety.. The globin tetramer is globular or ellipsoid in shape, being approximately 550nm in diameter. The four porphyrin heme moieties lie in four regularly spaced clefts on the tetramer surface.. The globin portion of most normal hemoglobins consists of two chains from chromosome 16 and two from chromosome 11. Normal a chains contain 141 amino acids; normal ß chains 146 amino acids. The d chain varies by 10 aa; the g chain by 39 aa compared with the ß chain ...
Annotated images of multiple alignments: HSs in the mammalian beta-globin LCR How to contact us NOTE: These pages are under constant revision, and are located on several physical systems. Please be careful to only bookmark our published URL, http://www.bx.psu.edu/, otherwise your links to internal pages may go stale. ...
Xenopus embryos contain a considerable amount of a polysialo-ganglioside not yet fully characterized; in this paper, we will refer to it as ganglioside XI. Preliminary experiments indicate asialo-GMI as the core structure of the ganglioside XI and pa
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
A team of scientists at the University of California, Davis, and the University of Auckland has discovered that neuroglobin may protect against Alzheimers disease by preventing brain neurons from dying in response to natural stress. A team of scientists at the University of California, Davis and the University of Auckland has discovered that neuroglobin may protect against Alzheimers disease by preventing brain neurons from dying in response to natural stress. The team published the results of their study in the April, 2010 issue of Apoptosis.. Scientists have learned that neuroglobin protects cells from stroke damage, amyloid toxicity and injury due to lack of oxygen. Neuroglobin occurs in various regions of the brain and at particularly high levels in brain cells called neurons. Scientists have associated low levels of neuroglobin in brain neurons with increased risk of Alzheimers disease. Recent studies have hinted that neuroglobin protects cells by maintaining the function of mitochondria ...
In 2015, a group of Chinese researchers repo--rted replacing a mutated gene that encodes the β-globin protein, a gene responsible for the development of β-thalassemia, in pre-implantation human embryos.1 While only 4 of the 86 embryos contained the replaced DNA, this discovery heralded the possibility of removing mutations and making epigenetic changes to the genome that could protect humans from diseases. It also adds a new level of complexity to decisions regarding changing the fate of future generations, a question that haunts many parents and policy workers today. With this advancement, expectant parents may have the ability to protect their children from certain diseases while also introducing them to novel, unanticipated ailments. Such advancement could thus blur the boundary between disease prevention and acceptance of genetic diversity. My father once told me the story of how a deaf girl grew up to become a professional clarinet player. Because of a recessive mutation, she had to learn ...
An example of a complex eukaryotic KOG: globins and related hemoproteins. The systematic protein names of the KOG members are listed under each species. To the
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The human HBB complex sequence is a compilation of sequences. Most of the sequences flanking the beta-like globin genes and LCR were determined by Mike Bulger in the Groudine lab, and he generated this compilation. A "minimal tiling path" of GenBank sequences that in combination will make something close to this compilation (after removing overlaps) is accession numbers AF137396, AF064190, U01317, AF137131, X54282, AF289203 and AF289204. THERE IS A ROUGHLY 6 KB GAP IN THE HUMAN SEQUENCE at position 344746. The gene HOR3beta3 and the 3 breakpoint for the Chinese thalassemia deletion precede this gap, and the 3 breakpoint for HPFH1 and the gene HOR3beta4 follow this gap. This gap was resistant to cloning and sequencing in multiple attempts. The Celera contig also ends in roughly this region. ...
Specific complementary DNAs (cDNAs) for the messenger RNAs coding for sheep alpha-, betaA-, betaB-, betaC-, and gamma-globins were prepared by thermal denaturation of heterologous hybrids (e.g. alphabetaB-cDNA-alphagamma-mRNA) followed by hydroxylapatite chromatography. Each cDNA represented a nearly full-length copy of its globin mRNA complement as determined by electrophoretic analysis in polyacrylamide gels containing 98% formamide. The purity of each cDNA fraction was estimated by hybridization analysis and thermal denaturation. The beta- and gamma-cDNAs contained 5 to 20% contaminating alpha-cDNA while the alpha-cDNA was 25 to 30% contaminated with non-alpha-cDNA. The melting temperatures (Tm) of homologous duplexes between each non-alpha chain cDNA and its mRNA complement ranged from 69.5-71.5 degrees in 50% formamide while alpha-alpha duplexes melted with a Tm of 75-76 degrees. The Tm values of heterologous duplexes formed between each non-alpha-cDNA and the various globin mRNAs (e.g
Click to launch & play an online audio visual presentation by Dr. Ann Dean on The beta-globin locus, part of a collection of online lectures.
Neuroglobin and Cytoglobin are two new heme-containing repiratory proteins, which were revealed through the human genome sequence. These proteins are both monomeric, and are structurally similar to myoglobin more than hemoglobin. The expression of neuroglobin is restricted to the brain and is mostly observed in the retina. Its roles include protecting neural tissue from hypoxia and insufficient oxygenation of the blood, through its roles in neuronal oxygen homeostasis. Cytoglobin on the other hand is expressed mainly in fibroblasts and other similar cells throughout the body, and may be involved in collagen synthesis. Spectroscopy data has shown that both proteins have the proximal and sital histidines coordinated to iron in the deoxy form and the distal histidine is displaced on oxygen binding.. ...
Cell death associated with mitochondrial dysfunction is common in acute neurological disorders and in neurodegenerative diseases. Neuronal apoptosis is regulated by multiple proteins, including neuroglobin, a small heme protein of ancient origin. Neuroglobin is found in high concentration in some neurons, and its high expression has been shown to promote survival of neurons in vitro and to protect brain from damage by both stroke and Alzheimers disease in vivo. Early studies suggested this protective role might arise from the proteins capacity to bind oxygen or react with nitric oxide. Recent data, however, suggests that neither of these functions is likely to be of physiological significance. Other studies have shown that neuroglobin reacts very rapidly with cytochrome c released from mitochondria during cell death, thus interfering with the intrinsic pathway of apoptosis. Systems level computational modelling suggests that the physiological role of neuroglobin is to reset the trigger level for the
ChIP qPCR primers: use in control reactions to amplify human GAPDH, RPL10, or beta globin loci from DNA isolated using chromatin immunoprecipitation.