Globins: A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.alpha-Globins: Members of the alpha-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 16. They include zeta-globin and alpha-globin. There are also pseudogenes of zeta (theta-zeta) and alpha (theta-alpha) in the cluster. Adult HEMOGLOBIN is comprised of 2 alpha-globin chains and 2 beta-globin chains.alpha-Thalassemia: A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted.Hylobates: A genus of the family HYLOBATIDAE consisting of six species. The members of this genus inhabit rain forests in southeast Asia. They are arboreal and differ from other anthropoids in the great length of their arms and very slender bodies and limbs. Their major means of locomotion is by swinging from branch to branch by their arms. Hylobates means dweller in the trees. Some authors refer to Symphalangus and Nomascus as Hylobates. The six genera include: H. concolor (crested or black gibbon), H. hoolock (Hoolock gibbon), H. klossii (Kloss's gibbon; dwarf siamang), H. lar (common gibbon), H. pileatus (pileated gibbon), and H. syndactylus (siamang). H. lar is also known as H. agilis (lar gibbon), H. moloch (agile gibbon), and H. muelleri (silvery gibbon).Hemoglobins, Abnormal: Hemoglobins characterized by structural alterations within the molecule. The alteration can be either absence, addition or substitution of one or more amino acids in the globin part of the molecule at selected positions in the polypeptide chains.Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.Fetal Hemoglobin: The major component of hemoglobin in the fetus. This HEMOGLOBIN has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by LEUKEMIA and several types of ANEMIA.Reticulocytes: Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.Chromosomes, Human, Pair 16: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Erythrocyte Count: The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.beta-Globins: Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the gene cluster. Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains.DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hemoglobin E: An abnormal hemoglobin that results from the substitution of lysine for glutamic acid at position 26 of the beta chain. It is most frequently observed in southeast Asian populations.Terminator Regions, Genetic: DNA sequences recognized as signals to end GENETIC TRANSCRIPTION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Leukemia, Erythroblastic, Acute: A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body.Hemoglobin A2: An adult hemoglobin component normally present in hemolysates from human erythrocytes in concentrations of about 3%. The hemoglobin is composed of two alpha chains and two delta chains. The percentage of HbA2 varies in some hematologic disorders, but is about double in beta-thalassemia.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Locus Control Region: A regulatory region first identified in the human beta-globin locus but subsequently found in other loci. The region is believed to regulate GENETIC TRANSCRIPTION by opening and remodeling CHROMATIN structure. It may also have enhancer activity.Hemoglobins: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Genes, Switch: Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation.gamma-Globins: Members of the beta-globin family. In humans, two non-allelic types of gamma-globin - A gamma and G gamma are encoded in the beta-globin gene cluster on CHROMOSOME 11. Two gamma-globin chains combine with two ZETA-GLOBIN chains to form the embryonic hemoglobin Portland. Fetal HEMOGLOBIN F is formed from two gamma-globin chains combined with two ALPHA-GLOBIN chains.Erythropoiesis: The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Erythroid Cells: The series of cells in the red blood cell lineage at various stages of differentiation.Anemia, Sickle Cell: A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.Iron Overload: An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. (From Churchill's Illustrated Medical Dictionary, 1989)Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Erythroid Precursor Cells: The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.Iron Chelating Agents: Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems.DNA, Recombinant: Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.Chromosome Deletion: Actual loss of portion of a chromosome.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Hemoglobin H: An abnormal hemoglobin composed of four beta chains. It is caused by the reduced synthesis of the alpha chain. This abnormality results in ALPHA-THALASSEMIA.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.Erythroblasts: Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.NF-E2 Transcription Factor, p45 Subunit: A tissue-specific subunit of NF-E2 transcription factor that interacts with small MAF PROTEINS to regulate gene expression. P45 NF-E2 protein is expressed primarily in MEGAKARYOCYTES; ERYTHROID CELLS; and MAST CELLS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.NF-E2 Transcription Factor: A basic-leucine zipper transcription factor that regulates GLOBIN gene expression and is related to TRANSCRIPTION FACTOR AP-1. NF-E2 consists of a small MAF protein subunit and a tissue-restricted 45 kDa subunit.Erythroid-Specific DNA-Binding Factors: A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.Blood Transfusion: The introduction of whole blood or blood component directly into the blood stream. (Dorland, 27th ed)Chromosomes, Artificial, Yeast: Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. These artificial chromosomes are used extensively in molecular biology for the construction of comprehensive genomic libraries of higher organisms.Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.Homozygote: An individual in which both alleles at a given locus are identical.Hemoglobin, Sickle: An abnormal hemoglobin resulting from the substitution of valine for glutamic acid at position 6 of the beta chain of the globin moiety. The heterozygous state results in sickle cell trait, the homozygous in sickle cell anemia.Sickle Cell Trait: The condition of being heterozygous for hemoglobin S.Pyridones: Pyridine derivatives with one or more keto groups on the ring.Deoxyribonuclease I: An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.K562 Cells: An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Hemoglobin J: A group of abnormal hemoglobins with similar electrophoretic characteristics. They have faster electrophoretic mobility and different amino acid substitutions in either the alpha or beta chains than normal adult hemoglobin. Some of the variants produce hematologic abnormalities, others result in no clinical disorders.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Erythrocytes, Abnormal: Oxygen-carrying RED BLOOD CELLS in mammalian blood that are abnormal in structure or function.GATA1 Transcription Factor: A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Hybrid Cells: Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.SicilyIntegrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Yolk Sac: The first of four extra-embryonic membranes to form during EMBRYOGENESIS. In REPTILES and BIRDS, it arises from endoderm and mesoderm to incorporate the EGG YOLK into the DIGESTIVE TRACT for nourishing the embryo. In placental MAMMALS, its nutritional function is vestigial; however, it is the source of INTESTINAL MUCOSA; BLOOD CELLS; and GERM CELLS. It is sometimes called the vitelline sac, which should not be confused with the VITELLINE MEMBRANE of the egg.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Kinetics: The rate dynamics in chemical or physical systems.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.Erythrocyte Indices: ERYTHROCYTE size and HEMOGLOBIN content or concentration, usually derived from ERYTHROCYTE COUNT; BLOOD hemoglobin concentration; and HEMATOCRIT. The indices include the mean corpuscular volume (MCV), the mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC).Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Ferritins: Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store IRON in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (APOFERRITINS) made of 24 subunits of various sequences depending on the species and tissue types.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes.MafK Transcription Factor: A small Maf protein involved in differentiation of ERYTHROID CELLS. MafK was originally described as the small subunit of the NF-E2 Transcription Factor, but other small MAF PROTEINS also serve as NF-E2 subunits.Hematopoiesis, Extramedullary: The formation and development of blood cells outside the BONE MARROW, as in the SPLEEN; LIVER; or LYMPH NODES.
Orkin SH, Michelson A (1980). "Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia". Nature. 286 ( ... 2001). "Embryonic and fetal globins are expressed in adult erythroid progenitor cells and in erythroid cell cultures". Prenat. ... while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene ... Hemoglobin subunit zeta is a protein that in humans is encoded by the HBZ gene. Zeta-globin is an alpha-like hemoglobin. The ...
... two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions). Deletion of ... the two genes that code for alpha globins, are non-functional, only gamma globins are produced. These gamma globins bind to ... four alpha globin genes was previously felt to be incompatible, but there are currently 69 patients who have survived past ... "Pathophysiology of alpha thalassemia". www.uptodate.com. Retrieved 2016-08-30. F. P. van der Dijs, M. Volmer, D. G. van Gijssel ...
Usually there are four genes that code for alpha globin and two genes that code for beta globin. If the genes for alpha chains ... Hb H usually occurs in some alpha thalassemia and is composed of four beta globin (protein) chains. This variant is usually ... Hemoglobin variants occur when there are genetic changes in specific genes, or globins, that cause changes or alterations in ... With most of these variants are mutations in the alpha globin gene that result in an abnormally long alpha chain and an ...
Frischknecht H, Dutly F (Mar 2007). "A 65 bp duplication/insertion in exon II of the beta globin gene causing beta0-thalassemia ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. PMID 2649166. Salzano AM, ... Many CRMs have been mapped within the cluster of genes encoding β-like globins expressed in embryonic (HBE1), fetal (HBG1 and ... This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. Expression of all of ...
1993). "Normal delta-globin gene sequences in Sardinian nondeletional delta beta-thalassemia". Hemoglobin. 16 (6): 503-9. doi: ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. PMID 2649166.. ... The order of the genes in the beta-globin cluster is: 5' - epsilon - gamma-G - gamma-A - delta - beta - 3'. ... The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains ...
Frischknecht H, Dutly F (2007). "A 65 bp duplication/insertion in exon II of the beta globin gene causing beta0-thalassemia". ... Expression of beta globin and the neighbouring globins in the β-globin locus is controlled by single locus control region (LCR ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. PMID 2649166. Giardina B, ... is a globin protein, which along with alpha globin (HBA), makes up the most common form of haemoglobin in adult humans, the HbA ...
The α- and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through ... "Hemoglobinopathies and Thalassemias". Retrieved 2007-12-26. Reed, Leslie. "Adaptation found in mouse genes." Omaha World-Herald ... Each protein chain arranges into a set of alpha-helix structural segments connected together in a globin fold arrangement. Such ... Since many of these proteins contain globins and the heme moiety (iron in a flat porphyrin support), they are often called ...
... protein subunits (genes): *Alpha globin 1. *Beta globin. *Delta globin. Hemoglobin compounds: *Carbaminohemoglobin ( ... "Hemoglobinopathies and Thalassemias". Retrieved 2007-12-26.. *^ Reed, Leslie. "Adaptation found in mouse genes." Omaha World- ... "Gene duplication, genome duplication, and the functional diversification of vertebrate globins". Molecular Phylogenetics and ... and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through ...
β-thalassemia, one of the most common congenital anemias, arises from partial or complete lack of β-globin synthesis. Excessive ... Hepcidin is a protein that in humans is encoded by the HAMP gene. Hepcidin is a key regulator of the entry of iron into the ... Pandur E, Nagy J, Poór VS, Sarnyai A, Huszár A, Miseta A, Sipos K (April 2009). "Alpha-1 antitrypsin binds preprohepcidin ... and also decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with ...
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 ...
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 - ...
... is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease. It is estimated that 7% of world's population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in populations from Africa, the Mediterranean basin and Southeast Asia. Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemias, in contrast, usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in ...
The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) in the year following birth. In the non-pathological condition known as hereditary persistence of fetal hemoglobin (HPFH), gamma globin expression is continued into adulthood. Also, in cases of beta-thalassemia and related conditions, gamma chain production may be maintained, possibly as a mechanism to compensate for the mutated beta-globin. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin ...
The Lamprey's Tale further develops the gene's eye view of ancestry and pedigree that earlier tales, The Eve's Tale and The Gibbon's Tale, alluded to. In human, four haemoglobin genes are known to be cousin genes of each other. An ancestor globin gene from an ancient vertebrate split into two genes, alpha and beta, which ended up in two different chromosomes and continued to evolve independently. Both alpha and beta further split into more independently evolving genes. All jawed fish show such alpha/beta split as predicated by evolution. However, lampreys and hagfish are ancient enough that they predate this gene split. In fact, jawless fishes, whenever investigated, do not possess split globin genes. As Dawkins explained in the chapter 'All Africa and her progenies' in his ...
Antidepresan kullanımının akut, hafif ya da orta düzey majör depresif bozukluk tedavisindeki etkinliliği hakkındaki araştırmalar birbiri ile aykırı düşen sonuçlar ortaya koymaktadır. Ağır ve kronik bozukluk tedavileri için ise antidepresanların faydalılığını destekleyen sonuçlar daha çok ve güçlüdür. Zıt araştırma sonuçları, ilaçların asıl etkisinden ziyade yayımlanan deneylere ilişkin kimi teknik sorunların varlığına atfedilmişse de; daha sonraları, yeni nesil antidepresanların genel faydalılığının klinik anlamlılık bakımından kriterleri sağlamadığı görüşü daha ağırlık kazanmıştır. National Institute for Health and Care Excellence tarafından görevlendirilen bir komisyonun hazırladığı bir literatür taramasında, SSRIların, plaseboya nispeten, orta ve ağır majör depresif bozukluk belirtilerini yarı yarıya azaltabildiğine işaret eden pek çok kanıtın mevcut olduğu ve benzer faydalılığın, daha ...
Bu gen tarafından kodlanan protein, eozinofil granülünün kristal çekirdeğinin baskın bir bileşenidir. Bu proteinin proformu, plasenta ve gebelik serumunda da yüksek düzeyde bulunur, burada gebelikle ilişkili plazma proteini A (PAPPA), anjiyotensinojen (AGT) ve C3dg de içinde olmak üzere diğer birçok proteinle kompleks halinde bulunur. Bu protein, sitotoksin ve helmint toksini olarak antiparazitik savunma mekanizmalarına ve immün aşırıduyarlılık tepkimelerine girebilir. Alerji hastalıklarında epitelyal hücre hasarı, eksfoliyasyon ve bronkospazm ile doğrudan ilişkilidir. PRG2, eozinofil granüllerinde baskın olan 117-kalıntı proteinidir. Helmintlere karşı etkili bir enzimdir ve in vitro bakteri ve memeli hücrelerine karşı toksiktir. Eozinofil majör bazik protein ayrıca mast hücrelerinden ve bazofillerden histamin salınmasını sağlar ve nötrofiller ile alveoler makrofajları etkinleştirir. ...
Gramovo farbenie zaviedol v roku 1884 Christian Gram. Je to diferenciačné farbenie založené na sfarbení gram-pozitívnych a gram-negatívnych buniek baktérií. Rozdiel medzi týmito dvoma bunkami je predovšetkým v ich bunkovej stene. Bunkové steny G+ baktérií majú oveľa hrubšiu vrstvu peptidoglykánu ako bunkové steny G- baktérií. G- bunky majú vo vonkajšej bunkovej stene aj množstvo lipidov.. Princíp Gramovo farbenia spočíva v tom, že sa obidve bunky (G+ aj G-) zafarbia farbivom kryštálovou violeťou, čím sa obe sfarbia do fialova. Preparát sa potom morí jódom v roztoku jodidu draselného, ktorý s farbivom vytvorí komplex v obidvoch bunkách. Potom sa farbivo vymýva etanolom (alebo acetónom), pričom komplex sa vyplavuje len z G- baktérií (rozpúšťa sa vonkajšia lipidová vrstva bunkovej steny), ktoré sa odfarbia. Napokon sa preparát dofarbuje karbolfuchsínom (alebo safranínom). G+ bunky teda po Gramovom farbení ostávajú fialové, G- bunky sú ...
Gramovo farbenie zaviedol v roku 1884 Christian Gram. Je to diferenciačné farbenie založené na sfarbení gram-pozitívnych a gram-negatívnych buniek baktérií. Rozdiel medzi týmito dvoma bunkami je predovšetkým v ich bunkovej stene. Bunkové steny G+ baktérií majú oveľa hrubšiu vrstvu peptidoglykánu ako bunkové steny G- baktérií. G- bunky majú vo vonkajšej bunkovej stene aj množstvo lipidov. Princíp Gramovo farbenia spočíva v tom, že sa obidve bunky (G+ aj G-) zafarbia farbivom kryštálovou violeťou, čím sa obe sfarbia do fialova. Preparát sa potom morí jódom v roztoku jodidu draselného, ktorý s farbivom vytvorí komplex v obidvoch bunkách. Potom sa farbivo vymýva etanolom (alebo acetónom), pričom komplex sa vyplavuje len z G- baktérií (rozpúšťa sa vonkajšia lipidová vrstva bunkovej steny), ktoré sa odfarbia. Napokon sa preparát dofarbuje karbolfuchsínom (alebo safranínom). G+ bunky teda po Gramovom farbení ostávajú fialové, G- bunky sú ...
Enterobacteriales, po slovensky aj enterobaktérie alebo gramnegatívne fakultatívne anaeróbne tyčinky, je rad baktérií s jedinou čeľaďou Enterobacteriaceae. Zahŕňa gramnegatívne, chemoorganotrofné, fakultatívne anaerobné a aerobné baktérie nachádzajúce sa vo vzduchu, vo vode a v pôde. Rozšírené sú v telách živočíchov od bezstavovcov až po človeka Ich rozšírenie je kozmopolitné. Tieto prokaryoty netvoria spóry, len puzdra. Puzdra majú polysacharidový základ, chránia bunku pred faktormi vonkajšieho prostredia, napríklad slnečným žiarením a dezinfekčnými prostriedkami. Kolónie niektorých neopuzdrených mikroorganizmov môžu získať opuzdrenie genetickým procesom transdukcie, takto obalom chránené bakteriálne organizmy sú virulentnejšie. Majú tvar paličiek širokých 0,1 až 1,5 µm. Bunkový pohyb sa uskutočňuje pomocou bičíkov (peritrichne usporiadaných), rad však zahŕňa aj nepohyblivé baktérie, bez bičíkov. Známe sú ich ...
Ribozómy sú bunkové organely nachádzajúce sa vo všetkých známych bunkách, čiže vo všetkých živých organizmoch okrem vírusov, pokiaľ sú pokladané za živé. Prebieha v nich syntéza bielkovín (proteínov) - proteosyntéza. Patria medzi najhojnejšie zastúpené bunkové organely. Sú uložené voľne v cytoplazme, u eukaryotov sú tiež vo vnútri plastidov, mitochondrií a viazané na endoplazmatické retikulum. Obsahujú ribonukleovú kyselinu (RNA) a bielkoviny, z chemického hľadiska preto patria medzi nukleoproteíny. Bielkoviny tvoria cca 1/3 obsahu ribozómu. Odlišujeme dva základné typy týchto organel (pre prokaryoty a eukaryoty). Eukaryoty však majú v semiautonómnych organelách ribozómy podobné prokaryotickým ribozómom a iba ich cytoplazmatické ribozómy sa označujú ako ribozómy eukaryotického typu. Každý ribozóm sa delí na dve podjednotky s odlišnými veľkosťami. K ribozómu sa napája tzv. mediátorová ribonukleová kyselina (mRNA), ktorá ...
Nástup digitálnej skiagrafie hrudníka viedol k rozvoju nových spôsobov zberu a spracovania údajov a následnej výstavby obrazu. Cieľom bola čo najvyššia možná kvalita snímky a zvýšenie citlivosti na čo najmenšie patologické zmeny. Zobrazovanie duálnou energiou (DEI, dual-energy imaging) spojené so následnou subtrakciou obrazov využíva vlastnosť kostí a mäkkých tkanív, ktoré majú odlišné absorpčné koeficienty rtg žiarenia v závislosti od použitej energie. Kombinácia dvoch snímok s odlišnou energiou (napr 40 a 120 kV) umožňuje napr. lepšie zobrazenie drobných pľúcnych nodulov a tiež určiť, či sú skalcifikované. Techniky temporálnej subtrakcie sú založené na možnosti subtrakcie dvoch snímok hrudníka konkrétneho pacienta, urobené v rôznom čase. Takáto subtrakcia odfiltruje štruktúry, ktoré sa v čase nezmenili a naopak zvýrazní zmeny, ktoré sa mohli objaviť na aktuálnej snímke. Zvyšuje tak šancu na diagnostiku včasných ...
Vo vývoji sú neinvazívne glukometre, ktoré merajú glykémiu spektroskopicky v krvi alebo v živom tkanive. Využívajú väčšinou absorpčnú spektroskopiu v blízkom alebo strednom infračervenom pásme alebo Ramanovu rozptylovú spektroskopiu. Niektoré prístroje sa už vyrábajú (rok 2017), ale majú problémy s presnosťou a kalibráciou. Ďalším smerom vo vývoji sú glukózové senzory, ktoré kontinuálne monitorujú koncentráciu glukózy v intersticiálnej tekutine podkožného tkaniva. Tieto zariadenia sa už niekoľko rokov používajú v praxi, hlavne u detských pacientov a u pacientov s veľmi nestabilným diabetom 1. typu, ale v súčasnosti (rok 2017) stále trpia krátkou životnosťou a sú potrebné ich časté kalibrácie (min. 1-2 denne). ...
... affected chromosome carries only a single active alpha globin gene; this condition is present in alpha thalassaemia ... Globins: 1583*Hemoglobins: 20443*Abnormal Hemoglobins: 107*Hemoglobin J: 9*hemoglobin J Tongariki: 1 ... alpha-Thalassemia 06/01/1982 - "Three identical alpha + thalassemia genes, one of which always carried the Hb J Tongariki ... alpha chain variant; affected chromosome carries only a single active alpha globin gene; this condition is present in alpha ...
Nevertheless, they fail to direct alpha globin synthesis in an interspecific hybrid containing the abnormal (alpha alpha)RA ... DNA sequence analysis has shown that the transcription units of both alpha genes downstream of this deletion are normal. ... We describe a family in which alpha-thalassemia occurs in association with a deletion of 62 kilobases from a region upstream of ... unidentified positive regulatory sequences analogous to those detected in a corresponding position of the human beta globin ...
As well as emphasising the ameliorating effect of α thalassaemia on HbE β thalassaemia the finding of a novel form of α(0) ... The patients with HbE β thalassaemia who had co-inherited α thalassaemia all showed an extremely mild phenotype and reduced ... thalassaemia in an ethnic minority, together with an unexpected diversity of forms of non-deletion α thalassaemia in Sri Lanka ... thalassaemia, one family carried a previously reported form of α(0) thalassaemia, --(THAI), and five families had different ...
... the lack of a specific characteristic comparable to the Hb A2 increase for beta thalassemias, and the almost complete homology ... alpha 3.7, -alpha 4.2, alpha Hphl, alpha Ncol, --MED, -(alpha)20.5, alpha alpha alpha anti3.7]. The electrophoretic patterns ... METHODS AND RESULTS A new set of PCR techniques, each based on primer(s) specific for a particular type of alpha globin gene ... They lead to the identification of all alpha globin disorders common in the Mediterranean area [- ...
Orkin SH, Michelson A (1980). "Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia". Nature. 286 ( ... 2001). "Embryonic and fetal globins are expressed in adult erythroid progenitor cells and in erythroid cell cultures". Prenat. ... while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene ... Hemoglobin subunit zeta is a protein that in humans is encoded by the HBZ gene. Zeta-globin is an alpha-like hemoglobin. The ...
... followed respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in management and prenatal diagnosis of ... the beta-thalassemia mutations should be considered first, ... play roles in modifying clinical symptoms of beta-thalassemia, ... The associations of SEA-alpha thalassemia 1, XmnI-Ggamma polymorphism and beta-globin gene mutations with the clinical severity ... The associations of SEA-alpha thalassemia 1, XmnI-Ggamma polymorphism and beta-globin gene mutations with the clinical severity ...
... is a blood disorder in which the body has a problem producing alpha globin, a component of hemoglobin, the ... About Alpha Thalassemia. Normally, each person has four genes for alpha globin. Alpha thalassemia happens when one or more of ... the genes that control the making of alpha globins is absent or defective. It can cause anemia ranging from mild to severe and ... Alpha globin is made by four genes and one or more can be mutated or missing, so there are four kinds of alpha thalassemia:. * ...
There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia. ... Thalassemia Definition Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of ... alpha globin, and beta globin. All types of thalassemia are caused by changes in either the alpha- or beta-globin gene. These ... Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than- ...
About Alpha Thalassemia. Normally, each person has four genes for alpha globin. Alpha thalassemia happens when one or more of ... the genes that control the making of alpha globins is absent or defective. It can cause anemia ranging from mild to severe and ... Alpha globin is made by four genes and one or more can be mutated or missing, so there are four kinds of alpha thalassemia:. * ... Alpha thalassemia: when the body has a problem producing alpha globin. *Beta thalassemia: when the body has a problem producing ...
We further show that vorinostat exhibits these synergistic beneficial effects in globin gene expression at nanomolar ... of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. Clinical ... have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin ... in addition to its beneficial effects for patients with β-thalassaemia through induction of γ-globin, has the potential to ...
New treatments and a potential cure using gene therapy are bringing new hope and health to individuals who suffer from this ... Association of alpha globin gene quadruplication and heterozygous beta thalassemia in patients with thalassemia intermedia. ... also called β-thalassemia major or Cooleys anemia. The resulting hemoglobin has two α-globins but no β-globins (β0), so it is ... Thalassemia trait. Individuals who inherit one mutated β-globin gene and one intact β-globin gene have β-thalassemia trait, or ...
... alpha- and beta-globins). In thalassemia minor or thalassemia trait (heterozygous thalassemia), also called alpha-thalassemia, ... Hemoglobin H disease is another form of thalassemia in which three of the four beta-globin genes are missing. ... Thalassemia People with mild thalassemia (alpha thalassemia trait or beta thalassemia minor) lead normal lives and do not ... Thalassemia. People with mild thalassemia (alpha thalassemia trait or beta thalassemia minor) lead normal lives and do not ...
... is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. ... Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage ... ... Background Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of ... alpha or beta globins. Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage and cell death ...
When one or more of the genes, controlling the formation of alpha globins is absent or defective it forms alpha thalassemia. ... The main components that make hemoglobin are of alpha globin and beta globin. ... Alpha Thalassemia is a group of blood illnesses that distress the system the body makes hemoglobin. Hemoglobin is a protein ... The alpha thalassemia market is expected to grow during forecast period owing to key factors such as... ...
Alpha thalassemia is an inherited anemia where the bone marrow has reduced production of alpha globin resulting in limited ... occurs when three alpha globin genes do not function. In this case, there are an excessive amount of beta globins. When these ... Hemoglobin H Constant Spring is a variant of alpha thalassemia where two alpha globin genes are lost plus one alpha globin gene ... occurs when one alpha globin gene is lost.. *Alpha thalassemia minor (or trait) occurs when two alpha globin genes are lost. ...
... alpha globin, and beta globin. All types of thalassemia are caused by changes in either the alpha- or beta-globin gene. These ... Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than- ... Alpha thalassemia major results from the deletion of all four alpha globin genes, such that there are no functioning alpha ... Alpha thalassemia major Because alpha globin is a necessary component of hemoglobin, absence of all functioning alpha globin ...
Alpha thalassaemia. Alpha thalassaemia is due to a deletion or mutation in one or more of the 4 alpha globin gene copies. The ... Haemoglobin refers to a family of compounds all made up of haem (an iron-containing complex), and various globins (protein ... the less alpha globin produced. The four different types of alpha thalassaemia include:. *Alpha thalassaemia trait (1 affected ... In particular in alpha thalassaemia it is important to know if a person with alpha thalassaemia trait has two mutated genes on ...
... urogenital abnormalities and alpha-thalassemia. The disease is caused by mutations in ATRX gene, which encodes a protein ... However, such gene was poorly expressed in blood mononuclear cells and its decrease was not confirmed in the quantitative real- ... The analysis of the expression pattern of the GRAF1/OPHN-1-L gene in human tissues and organs revealed the predominant brain ... cDNA microarray analysis showed that 35 genes had a lower expression (30-35% of controls) while 25 transcripts had a two-fold ...
... and β-globin genes, as well as in the distant regulatory elements, can cause thalassemia. Unbalanced production of globin ... the possibility of decreasing expression of the α-globin gene to improve the clinical severity of β-thalassemia could become a ... and experimental evidence suggests that altering globin chain imbalance by reducing the production of α-globin synthesis ... With the development of new genetic-based therapeutic tools that have a potential to decrease the expression of a selected gene ...
Alpha thalassemia. Alpha thalassemia is the result of changes in the genes for the alpha globin component of hemoglobin. There ... Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than- ... Alpha thalassemia trait occurs when two alpha globin genes are missing. This can occur in two ways. The genes may be deleted ... Alpha thalassemia major results from the deletion of all four alpha globin genes, such that there are no functioning alpha ...
Four genes are needed to make enough alpha globin protein chains. Alpha thalassemia trait occurs when one or two of the four ... Thalassemia is a quantitative problem of too few globins synthesized, whereas sickle-cell disease (a haemoglobinopathy) is a ... thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an ... has four protein chainstwo alpha globin and two beta globin. The two major types of thalassemia, alpha and beta, are named ...
... simple heterozygotes for the alpha 29Leu--,Pro mutation have the phenotype of alpha-thalassaemia trait. ... C transition in codon 29 of the alpha 2 gene causing a leucine--,proline substitution. Although this mutation would be expected ... Adult Anemia, Hypochromic/etiology Base Sequence Case Report Child, Preschool Codon/*genetics DNA/chemistry Female Globins/* ... A base substitution (T--,C) in codon 29 of the alpha 2-globin gene causes alpha thalassaemia ...
Thalassemia and Globin Gene Regulation: Hemoglobin Switching, November 29, 2018 The Role of Adenosine Monophosphate Activated ... adenosine monophosphate, ampk, gamma-globins, protein kinase, fetal hemoglobin, metformin, forkhead box protein o3, western ... AMPK, FOXO3, gamma and beta globin gene expression were measured by RT-qPCR and HbF by HPLC respectively on day 14 of culture. ... Cell lysate was collected on day 14, and AMPK, FOXO3, gamma and beta globin gene expression and protein levels measured by RT- ...
A review of the molecular genetics of the human alpha-globin gene cluster., Blood , 73(5), 1081-104, 1989 PubMed ... The expression of HBB and the neighbouring globins in the β-globin locus is controlled by a single locus control region (LCR), ... Total absence of HBB causes beta-zero-thalassaemia. Reduced amounts of detectable HBB causes beta-plus-thalassaemia. ... HBB is a globin protein, which along with alpha globin (HBA) makes up the most common form of haemoglobin in adult humans, the ...
... alpha-Globins, beta-Thalassemia ... Hughes Group - Gene Regulation and Human Disease * Milne Group ... Antigens, CD34, Butyric Acid, Cell Culture Techniques, Enzyme Inhibitors, Erythroid Cells, Gene Expression Profiling, Gene ... Sauka-Spengler Group - Gene Regulatory Networks in Development and Disease * Patel Group - Origins of Genotoxic metabolism and ... Selective silencing of α-globin by the histone demethylase inhibitor IOX1: a potentially new pathway for treatment of β- ...
MutationsType of thalassemiaControlling alpha globin productionMilder than beta thalassemiaAmount of alpha globinLess alpha globinSynthesisTypes of thalassemiasChainsGeneticDeletionComplicationsChromosome 16TraitHydropsHemoglobin H diseaseSeverityPhenotypeGroup of inherited disordersQuantitativeProteinsMediterraneanHumansCarriersTraitsPrevalenceScreening in the newborn periodHbA1AbnormalitiesDiseasesDisordersCarrierDescentCDNAShortly after birthAfrican-AmericansSymptomsMinorDeficientReduced or absentAnemiaMolecularPredominantlyMajorVariantEthnicDiseaseProduction
- At least three genetic factors including beta-thalassemia mutations, alpha-thalassemia, and XmnI-Ggamma polymorphism were shown to modify clinical symptoms in beta-thalassemia disease. (cdc.gov)
- To determine associations of beta-thalassemia mutations, SEA-alpha thalassemia 1, and XmnI-Ggamma polymorphism, and clinical severity of beta-thalassemia in northern Thailand. (cdc.gov)
- Eight beta-globin gene mutations (both beta0 and beta+) were found Twenty-nine point one percent of the patients had at least one XmnI-Ggamma site (XmnI-Ggamma: +) and 4.1% of the patients were heterozygote for the SEA-alpha thalassemia 1. (cdc.gov)
- The beta-globin gene mutations showed maximal impact and the XmnI-Ggamma polymorphism had minimal influence on clinical severity in this cohort. (cdc.gov)
- Although these three genetic factors play roles in modifying clinical symptoms of beta-thalassemia, the beta-thalassemia mutations should be considered first, followed respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in management and prenatal diagnosis of beta-thalassemia in northern Thailand. (cdc.gov)
- The correlation of α-globin gene mutations and the XmnI polymorphism with clinical severity of Hb E/β-thalassemia. (cdc.gov)
- According to a widely accepted theory, most genetic changes - mutations - that cause thalassemia occurred multiple generations ago. (encyclopedia.com)
- The molecular defects causing β-thalassemia are point mutations predominantly found within and around the β-globin gene which result in reduced or absent synthesis of β-globin 10 . (nature.com)
- The clinical and genetic data accumulated over several decades through naturally occurring human mutations have identified, two independent pathways that could counter-act the globin imbalance in order to ameliorate the severity of β-thalassaemia 12 . (nature.com)
- Background Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. (mendeley.com)
- Alpha thalassemias result from changes (mutations) in these genes. (healthofchildren.com)
- Mutations in the genes coding for the globin chains can cause disorders in haemoglobin production. (labtestsonline.org.au)
- Thalassaemias are a group of disorders in which mutations in one or more of the alpha or beta globin genes cause a reduction in the amount of the HbA produced. (labtestsonline.org.au)
- The disease is caused by mutations in ATRX gene, which encodes a protein belonging to the SWI/SNF DNA helicase family, a group of proteins involved in the regulation of gene transcription at the chromatin level. (biomedcentral.com)
- Thalassemias usually result in under production of normal globin proteins, often through mutations in regulatory genes. (dailystrength.org)
- This circumstance substantially reduces the amount of alpha globin that the body produces. (healthofchildren.com)
- With this condition, the large decrease in the amount of alpha globin chains produced causes an excess of beta chains which then aggregate into beta4 tetramers (groups of 4 beta chains), known as haemoglobin H. HbH disease can cause moderate to severe anaemia and splenomegaly (enlarged spleen). (labtestsonline.org.au)
- Nevertheless, they fail to direct alpha globin synthesis in an interspecific hybrid containing the abnormal (alpha alpha)RA chromosome. (ox.ac.uk)
- Unbalanced production of α-globin in the presence of defective synthesis of β-globin is the primary mechanism for anaemia in β-thalassaemia. (nature.com)
- The thalassaemias are usually classified by the type of globin chain whose synthesis is reduced. (labtestsonline.org.au)
- Unbalanced production of globin chains owing to defective synthesis of one, and the continued unopposed synthesis of another, is the central causative factor in the cellular pathology and pathophysiology of thalassemia. (ox.ac.uk)
- A large body of clinical, genetic, and experimental evidence suggests that altering globin chain imbalance by reducing the production of α-globin synthesis ameliorates the disease severity in patients with β-thalassemia. (ox.ac.uk)
- In thalassemia, the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. (dailystrength.org)
- Reduced synthesis of one of the globin chains causes the formation of abnormal haemoglobin molecules, and this in turn causes the anemia which is the characteristic presenting symptom of the thalassemias. (dailystrength.org)
- Thalassemia is a quantitative problem of too few globins synthesized, whereas sickle-cell disease (a haemoglobinopathy) is a qualitative problem of synthesis of a non-functioning globin. (dailystrength.org)
- This unbalanced production of α- and β-like globin chains leads to precipitation of free α-globin chains in red blood cells (RBC) and their precursors to cause haemolysis and ineffective erythropoiesis which are considered as the primary pathophysiological mechanism for the anaemia in thalassaemia 11 . (nature.com)
- Abnormally unpaired globin chains cause haemolytic anaemia by causing membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow. (mendeley.com)
- Hemoglobin A (the major hemoglobin in adults) contains two alpha globin chains and two beta globin chains. (verywellhealth.com)
- Haemoglobin refers to a family of compounds all made up of haem (an iron-containing complex), and various globins (protein chains that surround the haem complex). (labtestsonline.org.au)
- HbA contains two alpha (α) protein chains and two beta (ß) chains. (labtestsonline.org.au)
- HbF has two alpha (α) and two gamma (γ) chains. (labtestsonline.org.au)
- There are 4 genes that code for alpha globin chains and 2 genes that code for the beta globin chains. (labtestsonline.org.au)
- The thalassemias are classified according to which chain of the hemoglobin molecule is affected (see hemoglobin for a description of the chains). (dailystrength.org)
- globin chains are encoded by two closely linked genes on chromosome 16. (dailystrength.org)
- Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling. (semanticscholar.org)
- Beta thalassemia causes variable anemia that can range from moderate to severe, depending in part on the exact genetic change underlying the disease. (encyclopedia.com)
- The thalassemias are among the most common genetic diseases worldwide. (encyclopedia.com)
- Clinical genetic data accumulated over three decades have clearly demonstrated that direct suppression of α-globin and induction of γ-globin are effective in reducing the globin chain imbalance in erythroid cells hence improving the clinical outcome of patients with β-thalassaemia. (nature.com)
- β-Thalassaemia is one of the most common genetic diseases with over 70,000 new patients diagnosed throughout the world every year 1 . (nature.com)
- Thalassemia is a genetic disorder. (healthofchildren.com)
- With the development of new genetic-based therapeutic tools that have a potential to decrease the expression of a selected gene in a tissue-specific manner, the possibility of decreasing expression of the α-globin gene to improve the clinical severity of β-thalassemia could become a reality. (ox.ac.uk)
- Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha globin gene cluster. (ox.ac.uk)
- We describe a family in which alpha-thalassemia occurs in association with a deletion of 62 kilobases from a region upstream of the alpha globin genes. (ox.ac.uk)
- DNA sequence analysis has shown that the transcription units of both alpha genes downstream of this deletion are normal. (ox.ac.uk)
- It seems probable that previously unidentified positive regulatory sequences analogous to those detected in a corresponding position of the human beta globin cluster are removed by this deletion. (ox.ac.uk)
- As well as the common deletion forms of α(+) thalassaemia three families from an ethnic minority were found to carry a novel form of α(0) thalassaemia, one family carried a previously reported form of α(0) thalassaemia, --(THAI), and five families had different forms of non-deletional thalassaemia. (ox.ac.uk)
- As well as emphasising the ameliorating effect of α thalassaemia on HbE β thalassaemia the finding of a novel form of α(0) thalassaemia in an ethnic minority, together with an unexpected diversity of forms of non-deletion α thalassaemia in Sri Lanka, further emphasises the critical importance of micro-mapping populations for determining the frequency of clinically important forms of the disease. (ox.ac.uk)
- alpha-Thalassemia 2, 3.7 kb deletion and hemoglobin AC heterozygosity in pregnancy: a molecular and hematological analysis. (semanticscholar.org)
- Coexistence of rare variant HbD Punjab [α2β2(121(Glu→Gln))] and alpha 3.7 kb deletion in a young boy of Hindu family in West Bengal, India. (semanticscholar.org)
- Alpha thalassaemia is due to a deletion or mutation in one or more of the 4 alpha globin gene copies. (labtestsonline.org.au)
- With thalassemia, the red blood cells are destroyed at a faster rate, leading to anemia , a condition that can cause fatigue and other complications. (kidshealth.org)
- and failure to deal with dental and orthodontic complications in people with thalassaemia exacerbates the public health, financial and personal burden posed by the condition. (mendeley.com)
- There exists a lack of evidence-based guidelines for care-seekers and providers to best deal with such dental and orthodontic complications in thalassaemia, which this review seeks to address. (mendeley.com)
- Objectives The main objective of this review was to assess different methods to treat dental and orthodontic complications in people with thalassaemia. (mendeley.com)
- Selection criteria We searched for published or unpublished randomised controlled trials for treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, gender and ethnic origin. (mendeley.com)
- This review highlights the need for conducting and appropriate reporting, of high-quality randomised controlled trials investigating the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. (mendeley.com)
- When a child has alpha thalassemia, there is a change in chromosome 16. (kidshealth.org)
- Alpha globin is made on chromosome 16. (kidshealth.org)
- When the two alpha globin genes lost are on the same chromosome 16 is called cis , but when one alpha globin gene is missing on each copy of chromosome 16 this is called trans . (verywellhealth.com)
- Two missing or mutated genes is a condition called alpha thalassemia minor or having alpha thalassemia trait . (kidshealth.org)
- In fact, the thalassemia trait is protective against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. (encyclopedia.com)
- Alpha-thalassemia trait is seen with increased frequency in the same ethnic groups. (encyclopedia.com)
- The frequency of hemoglobin H disease and alpha thalassemia major depends on the type of alpha thalassemia trait. (encyclopedia.com)
- Alpha thalassemia minor (or trait) occurs when two alpha globin genes are lost. (verywellhealth.com)
- In general, if iron deficiency anemia is ruled out and beta thalassemia trait is ruled out, the patient has alpha thalassemia trait. (verywellhealth.com)
- In the United States, up to 30 percent of African Americans are thought to be carriers for alpha thalassemia traits, meaning that they show no symptoms of the disorder but can pass the trait to their offspring. (healthofchildren.com)
- Often these individuals are identified only after having a child with HbH disease or alpha thalassaemia trait. (labtestsonline.org.au)
- Patients who have alpha thalassaemia trait have smaller ( microcytic ), paler ( hypochromic ) red blood cells and a mild chronic anaemia but do not generally experience any symptoms. (labtestsonline.org.au)
- Diagnosis of alpha thalassaemia trait is usually by exclusion of other causes of microcytic anaemia. (labtestsonline.org.au)
- Four missing or mutated genes is a condition known as alpha thalassemia major or hydrops fetalis . (kidshealth.org)
- Hydrops fetalis occurs when all four alpha globin genes are lost. (verywellhealth.com)
- Hydrops fetalis occurs when both parents have cis alpha thalassemia minor. (verywellhealth.com)
- The loss of four alpha globin genes is found during the work-up for the cause of hydrops. (verywellhealth.com)
- Alpha thalassemia major, sometimes called hemoglobin Barts or hydrops fetalis, is a fatal disease that results in severe anemia that begins even before birth. (healthofchildren.com)
- Three missing or mutated genes is called hemoglobin H disease . (kidshealth.org)
- There are two main types of alpha thalassemia disease: hemoglobin H disease and alpha thalassemia major. (encyclopedia.com)
- If one parent has cis alpha thalassemia minor (aa/--) and the other parent has trans alpha thalassemia minor (a-/a-), they have a 1 in 2 chance of having a child with Hemoglobin H disease. (verywellhealth.com)
- Individuals with hemoglobin H disease have inherited one completely defective gene and one gene that has one rather than two functional loci. (healthofchildren.com)
- Despite this estimate, the number of babies born with hemoglobin H disease or alpha thalassemia major is very low. (healthofchildren.com)
- Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin, the oxygen-carrying protein inside the red blood cells. (encyclopedia.com)
- Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin. (healthofchildren.com)
- Thalassaemia is a group of inherited disorders that affect the amount of haemoglobin a person produces. (labtestsonline.org.au)
- The majority of these births occur in the traditional thalassaemia belt which extends from the Mediterranean through the middle east and sub-Saharan Africa to south and southeast Asia 2 . (nature.com)
- Alpha thalassemia is commonly associated with Asia, Africa, and the Mediterranean area. (verywellhealth.com)
- Thalassemias are particularly associated with Arab-Americans, people of Mediterranean origin, and Asians. (dailystrength.org)
- People who are carriers of a thalassemia gene show no thalassemia symptoms and might not know they're carriers. (kidshealth.org)
- Silent alpha thalassemia carriers have no signs or symptoms of the disease, but are able to pass thalassemia on to their children. (kidshealth.org)
- Unaffected carriers of all types of thalassemia traits do not experience health problems. (encyclopedia.com)
- Alpha thalassemia is an inherited condition and requires both parents to be carriers. (verywellhealth.com)
- Carriers can pass on the affected gene to their offspring. (labtestsonline.org.au)
- Genes are "building blocks" that play an important role in determining physical traits and many other things about us. (kidshealth.org)
- The nucleus contains DNA (deoxyribonucleic acid), a long, spiral-shaped molecule that stores the genes that determine hair color, eye color, whether or not a person is right- or left-handed, and many more traits. (kidshealth.org)
- As populations migrated, so did the thalassemia traits. (encyclopedia.com)
- However, there are different types of alpha thalassemia traits within these populations. (encyclopedia.com)
- Confirmatory testing by DNA analysis is an important part of the testing process for Alpha thalassaemia because there are two copies (HbA1 and HbA2) of the alpha-chain gene on each chromosome. (labtestsonline.org.au)
- thalassemias involve the genes HBA1 (Online 'Mendelian Inheritance in Man' (OMIM) 141800) and HBA2 (Online 'Mendelian Inheritance in Man' (OMIM) 141850), inherited in a Mendelian recessive fashion. (dailystrength.org)
- Although both classes of thalassemia affect the same protein, the alpha and beta thalassemias are distinct diseases that affect the body in different ways. (encyclopedia.com)
- The two diseases are quite different from beta thalassemia as well as from one another. (encyclopedia.com)
- Although both alpha and beta thalassemias affect hemoglobin, these diseases affect the body in distinctly different ways. (healthofchildren.com)
- The highest frequency of alpha thalassemia diseases occurs in individuals of Southeast Asian and Chinese descent. (healthofchildren.com)
- Detection of alpha-globin gene disorders by a simple PCR methodology. (semanticscholar.org)
- Thalassemias are a group of blood disorders that affect the way the body makes hemoglobin. (kidshealth.org)
- There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia. (encyclopedia.com)
- In order to identify specific genes involved in the pathogenesis of the disease, we compared, by cDNA microarray, the expression levels of approximately 8500 transcripts between ATRX and normal males of comparable age. (biomedcentral.com)
- cDNA microarray analysis showed that 35 genes had a lower expression (30-35% of controls) while 25 transcripts had a two-fold higher expression in comparison to controls. (biomedcentral.com)
- If both parents have trans alpha thalassemia minor (a-/a-), all of their children with will have trans alpha thalassemia minor. (verywellhealth.com)
- Occasionally alpha thalassemia minor is identified on newborn screen , but not in all cases. (verywellhealth.com)
- Many people with alpha thalassemia minor I have no idea. (verywellhealth.com)
- No treatment is needed for alpha thalassemia minima or minor. (verywellhealth.com)
- People with alpha thalassemia minor will have lifelong mild anemia. (verywellhealth.com)
- Individuals with alpha thalassemia major have inherited two completely defective genes, one from each parent. (healthofchildren.com)
- One study of 500 pregnant women in northern Thailand estimated a frequency of one in 500 pregnancies affected by alpha thalassemia major, for example. (healthofchildren.com)
- Fetuses affected by alpha thalassaemia major become anaemic early in pregnancy. (labtestsonline.org.au)
- Hemoglobin H Constant Spring is a variant of alpha thalassemia where two alpha globin genes are lost plus one alpha globin gene is mutated. (verywellhealth.com)
- The analysis of the expression pattern of the GRAF1/OPHN-1-L gene in human tissues and organs revealed the predominant brain expression of a novel splicing isoform, called variant-3. (biomedcentral.com)
- We show that vorinostat directly reduces the production of α-globin whilst inducing the expression of γ-globin in human erythroid cells without perturbing erythroid proliferation, viability, differentiation or global gene expression. (nature.com)
- Two spots (called loci) on these genes control alpha globin production. (healthofchildren.com)