A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
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.
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.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
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.
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).
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.
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.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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)
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.
An individual having different alleles at one or more loci regarding a specific character.
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.
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.
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).
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)
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Any method used for determining the location of and relative distances between genes on a chromosome.
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.
Actual loss of portion of a chromosome.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
DNA sequences recognized as signals to end GENETIC TRANSCRIPTION.
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.
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.
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.
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.
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.
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.
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.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.
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.
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.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
The series of cells in the red blood cell lineage at various stages of differentiation.
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.
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.
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 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.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
The rate dynamics in chemical or physical systems.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.
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.
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.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
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.
The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.
Proteins prepared by recombinant DNA technology.
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.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.
Brain waves characterized by a relatively high voltage or amplitude and a frequency of 8-13 Hz. They constitute the majority of waves recorded by EEG registering the activity of the parietal and occipital lobes when the individual is awake, but relaxed with the eyes closed.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
An integrin alpha subunit that occurs as alternatively spliced isoforms. The isoforms are differentially expressed in specific cell types and at specific developmental stages. Integrin alpha3 combines with INTEGRIN BETA1 to form INTEGRIN ALPHA3BETA1 which is a heterodimer found primarily in epithelial cells.
Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
A family of hemoglobin-like proteins found in BACTERIA; PLANTS; and unicellular eukaryotes. Truncated hemoglobins are distantly related to vertebrate hemoglobins and are typically shorter than vertebrate hemoglobins by 20-40 residues.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
Drugs that selectively bind to and activate alpha adrenergic receptors.
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.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.
A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.
Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.

Pathophysiology of beta thalassemia--a guide to molecular therapies. (1/78)

The central mechanism underlying the pathophysiology of the beta thalassemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and survival. An imbalance of the alpha/non-alpha globin chains leads to an excess of unmatched alpha globin which precipitates out, damaging membrane structures leading to accelerated apoptosis and premature destruction of the erythroid precursors in the bone marrow (ineffective erythropoiesis). Close observation of the genotype/phenotype relationships confirms the pathophysiological mechanism and provides clues to molecular therapies, all of which aim to reduce the alpha/non-alpha chain imbalance. They include inheritance of the milder forms of beta thalassemia, co-inheritance of alpha thalassemia, or genetic factors (quantitative trait loci, QTLs) for increasing gamma globin expression. Currently, the most promising molecular therapeutic approaches include increasing beta globin gene expression by stem cell gene therapy and increasing gamma globin expression using pharmacological agents or by transduction of the gamma globin genes.  (+info)

Fetal globin induction--can it cure beta thalassemia? (2/78)

The beta thalassemias are one of a few medical conditions in which reactivation of a gene product that is expressed during fetal life can functionally replace a deficiency of essential proteins expressed at a later developmental stage. The fetal globin genes are present and normally integrated in hematopoietic stem cells, and at least one fetal gene appears accessible for reactivation, particularly in beta degrees thalassemia. However, rapid cellular apoptosis from alpha globin chain precipitation, and relatively low levels of endogenous erythropoietin (EPO) in some beta(+) thalassemia patients contribute to the anemia in beta thalassemia syndromes. In clinical trials, three classes of therapeutics have demonstrated proof-of-principle of this approach by raising total hemoglobin levels by 1-4 g/dL above baseline in thalassemia patients: EPO preparations, short chain fatty acid derivatives (SCFADs), and chemotherapeutic agents. Although thalassemic erythrocytes survive only for a few days, the magnitude of these responses is similar to those induced by rhu-EPO in anemic conditions of normal erythrocyte survival. New oral therapeutic candidates, which stimulate both fetal globin gene expression and erythropoiesis, and combinations of therapeutics with complementary molecular actions now make this gene-reactivation approach feasible to produce transfusion independence in many patients. Development of the candidate therapeutics is hindered largely by costs of drug development for an orphan patient population.  (+info)

Controlling alpha-globin: a review of alpha-globin expression and its impact on beta-thalassemia. (3/78)

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Mutations in the paralogous human alpha-globin genes yielding identical hemoglobin variants. (4/78)

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Mir-144 selectively regulates embryonic alpha-hemoglobin synthesis during primitive erythropoiesis. (5/78)

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Regulation of human alpha-globin gene expression and alpha-thalassemia. (6/78)

Hemoglobin and globin genes are important models for studying protein and gene structure, function and regulation. We reviewed the main aspects of regulation of human alpha-globin synthesis, encoded by two adjacent genes (alpha(2) and alpha(1)) clustered on chromosome 16. Their expression is controlled mainly by a regulatory element located 40 kb upstream on the same chromosome, the alpha-major regulatory element, whose activity is restricted to a core fragment of 350 bp, within which several regulatory protein binding sites have been found. Natural deletions involving alpha-major regulatory element constitute a particular category of alpha-thalassemia determinants in which the alpha-globin genes are physically intact but functionally inactive.  (+info)

Synthesis and secretion of hemoglobin by retinal pigment epithelium. (7/78)

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Study of spatial organization of chicken alpha-globin gene domain by 3C technique. (8/78)

This work deals with 3C (Chromosome Conformation Capture) analysis of the chicken alpha-globin gene domain in embryonic erythrocytes and lymphoid cells. Ligation products were quantitatively analyzed by real-time PCR with TaqMan probes. It was found that in lymphoid cells, where alpha-globin gene is not active, the domain has a relatively extended configuration. In embryonic erythrocytes that transcribe alpha(D) and alpha(A) genes, simultaneous interaction of several domain elements was revealed including the major regulatory element, the erythroid-specific DNase I hypersensitive site at a distance of 9 kb upstream from the alpha-globin gene cluster (-9 DHS), promoter of the housekeeping gene CGTHBA, the alpha(D)-globin gene promoter, and the erythroid-specific enhancer located after the alpha-globin gene cluster. We suppose that such interaction is necessary to provide for the active transcription status of the chicken alpha-globin gene domains in erythroid cells.  (+info)

Globins are a group of proteins that contain a heme prosthetic group, which binds and transports oxygen in the blood. The most well-known globin is hemoglobin, which is found in red blood cells and is responsible for carrying oxygen from the lungs to the body's tissues. Other members of the globin family include myoglobin, which is found in muscle tissue and stores oxygen, and neuroglobin and cytoglobin, which are found in the brain and other organs and may have roles in protecting against oxidative stress and hypoxia (low oxygen levels). Globins share a similar structure, with a folded protein surrounding a central heme group. Mutations in globin genes can lead to various diseases, such as sickle cell anemia and thalassemia.

Alpha-globins are a type of globin protein that combine to form the alpha-globin chains of hemoglobin, the oxygen-carrying protein in red blood cells. Hemoglobin is composed of four globin chains, two alpha-globin chains and two beta-globin chains, that surround a heme group. The alpha-globin genes are located on chromosome 16 and are essential for normal hemoglobin function. Mutations in the alpha-globin genes can lead to various forms of hemoglobin disorders such as alpha-thalassemia.

Thalassemia is a group of inherited genetic disorders that affect the production of hemoglobin, a protein in red blood cells responsible for carrying oxygen throughout the body. The disorder results in less efficient or abnormal hemoglobin, which can lead to anemia, an insufficient supply of oxygen-rich red blood cells.

There are two main types of Thalassemia: alpha and beta. Alpha thalassemia occurs when there is a problem with the alpha globin chain production, while beta thalassemia results from issues in beta globin chain synthesis. These disorders can range from mild to severe, depending on the number of genes affected and their specific mutations.

Severe forms of Thalassemia may require regular blood transfusions, iron chelation therapy, or even a bone marrow transplant to manage symptoms and prevent complications.

Human chromosome pair 16 consists of two rod-shaped structures present in the nucleus of each cell in the human body. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex structure called a chromatin.

Chromosomes come in pairs, with one chromosome inherited from each parent. Chromosome pair 16 contains two homologous chromosomes, which are similar in size, shape, and genetic content but may have slight variations due to differences in the DNA sequences inherited from each parent.

Chromosome pair 16 is one of the 22 autosomal pairs, meaning it contains non-sex chromosomes that are present in both males and females. Chromosome 16 is a medium-sized chromosome, and it contains around 2,800 genes that provide instructions for making proteins and regulating various cellular processes.

Abnormalities in chromosome pair 16 can lead to genetic disorders such as chronic myeloid leukemia, some forms of mental retardation, and other developmental abnormalities.

Alpha-thalassemia is a genetic disorder that affects the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. It is caused by deletions or mutations in the genes that produce the alpha-globin chains of hemoglobin.

There are several types of alpha-thalassemia, ranging from mild to severe. The most severe form, called hydrops fetalis, occurs when all four alpha-globin genes are deleted or mutated. This can cause stillbirth or death shortly after birth due to heart failure and severe anemia.

Less severe forms of alpha-thalassemia can cause mild to moderate anemia, which may be asymptomatic or associated with symptoms such as fatigue, weakness, and jaundice. These forms of the disorder are more common in people from Mediterranean, Southeast Asian, and African backgrounds.

Treatment for alpha-thalassemia depends on the severity of the condition and may include blood transfusions, iron chelation therapy, or occasionally stem cell transplantation.

"Hylobates" is not a medical term, but a biological genus name. It refers to a group of small, tailless primates known as gibbons or lesser apes, which are native to the forests of Southeast Asia. They are known for their agility in moving through trees by brachiation (arm-over-arm swinging).

There are currently 10 species recognized in the genus Hylobates, including the lar gibbon, agile gibbon, and siamang. While not a medical term, understanding the natural history of animals like gibbons can be important for medical professionals who work with them or study their diseases, as well as for conservationists and others interested in their welfare.

Beta-thalassemia is a genetic blood disorder that affects the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Specifically, beta-thalassemia is caused by mutations in the beta-globin gene, which leads to reduced or absent production of the beta-globin component of hemoglobin.

There are two main types of beta-thalassemia:

1. Beta-thalassemia major (also known as Cooley's anemia): This is a severe form of the disorder that typically becomes apparent in early childhood. It is characterized by a significant reduction or absence of beta-globin production, leading to anemia, enlarged spleen and liver, jaundice, and growth retardation.
2. Beta-thalassemia intermedia: This is a milder form of the disorder that may not become apparent until later in childhood or even adulthood. It is characterized by a variable reduction in beta-globin production, leading to mild to moderate anemia and other symptoms that can range from nonexistent to severe.

Treatment for beta-thalassemia depends on the severity of the disorder and may include blood transfusions, iron chelation therapy, and/or bone marrow transplantation. In some cases, genetic counseling and prenatal diagnosis may also be recommended for families with a history of the disorder.

Beta-globins are the type of globin proteins that make up the beta-chain of hemoglobin, the oxygen-carrying protein in red blood cells. Hemoglobin is composed of four polypeptide chains, two alpha-globin and two beta-globin chains, arranged in a specific structure. The beta-globin gene is located on chromosome 11, and mutations in this gene can lead to various forms of hemoglobin disorders such as sickle cell anemia and beta-thalassemia.

Abnormal hemoglobins refer to variants of the oxygen-carrying protein found in red blood cells, which differ from the normal adult hemoglobin (HbA) in terms of their structure and function. These variations can result from genetic mutations that affect the composition of the globin chains in the hemoglobin molecule. Some abnormal hemoglobins are clinically insignificant, while others can lead to various medical conditions such as hemolytic anemia, thalassemia, or sickle cell disease. Examples of abnormal hemoglobins include HbS (associated with sickle cell anemia), HbC, HbE, and HbF (fetal hemoglobin). These variants can be detected through specialized laboratory tests, such as hemoglobin electrophoresis or high-performance liquid chromatography (HPLC).

Reticulocytes are immature red blood cells that still contain remnants of organelles, such as ribosomes and mitochondria, which are typically found in developing cells. These organelles are involved in the process of protein synthesis and energy production, respectively. Reticulocytes are released from the bone marrow into the bloodstream, where they continue to mature into fully developed red blood cells called erythrocytes.

Reticulocytes can be identified under a microscope by their staining characteristics, which reveal a network of fine filaments or granules known as the reticular apparatus. This apparatus is composed of residual ribosomal RNA and other proteins that have not yet been completely eliminated during the maturation process.

The percentage of reticulocytes in the blood can be used as a measure of bone marrow function and erythropoiesis, or red blood cell production. An increased reticulocyte count may indicate an appropriate response to blood loss, hemolysis, or other conditions that cause anemia, while a decreased count may suggest impaired bone marrow function or a deficiency in erythropoietin, the hormone responsible for stimulating red blood cell production.

A gene is a specific sequence of nucleotides in DNA that carries genetic information. Genes are the fundamental units of heredity and are responsible for the development and function of all living organisms. They code for proteins or RNA molecules, which carry out various functions within cells and are essential for the structure, function, and regulation of the body's tissues and organs.

Each gene has a specific location on a chromosome, and each person inherits two copies of every gene, one from each parent. Variations in the sequence of nucleotides in a gene can lead to differences in traits between individuals, including physical characteristics, susceptibility to disease, and responses to environmental factors.

Medical genetics is the study of genes and their role in health and disease. It involves understanding how genes contribute to the development and progression of various medical conditions, as well as identifying genetic risk factors and developing strategies for prevention, diagnosis, and treatment.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

DNA restriction enzymes, also known as restriction endonucleases, are a type of enzyme that cut double-stranded DNA at specific recognition sites. These enzymes are produced by bacteria and archaea as a defense mechanism against foreign DNA, such as that found in bacteriophages (viruses that infect bacteria).

Restriction enzymes recognize specific sequences of nucleotides (the building blocks of DNA) and cleave the phosphodiester bonds between them. The recognition sites for these enzymes are usually palindromic, meaning that the sequence reads the same in both directions when facing the opposite strands of DNA.

Restriction enzymes are widely used in molecular biology research for various applications such as genetic engineering, genome mapping, and DNA fingerprinting. They allow scientists to cut DNA at specific sites, creating precise fragments that can be manipulated and analyzed. The use of restriction enzymes has been instrumental in the development of recombinant DNA technology and the Human Genome Project.

Nucleic acid hybridization is a process in molecular biology where two single-stranded nucleic acids (DNA, RNA) with complementary sequences pair together to form a double-stranded molecule through hydrogen bonding. The strands can be from the same type of nucleic acid or different types (i.e., DNA-RNA or DNA-cDNA). This process is commonly used in various laboratory techniques, such as Southern blotting, Northern blotting, polymerase chain reaction (PCR), and microarray analysis, to detect, isolate, and analyze specific nucleic acid sequences. The hybridization temperature and conditions are critical to ensure the specificity of the interaction between the two strands.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

A heterozygote is an individual who has inherited two different alleles (versions) of a particular gene, one from each parent. This means that the individual's genotype for that gene contains both a dominant and a recessive allele. The dominant allele will be expressed phenotypically (outwardly visible), while the recessive allele may or may not have any effect on the individual's observable traits, depending on the specific gene and its function. Heterozygotes are often represented as 'Aa', where 'A' is the dominant allele and 'a' is the recessive allele.

Recombinant DNA is a term used in molecular biology to describe DNA that has been created by combining genetic material from more than one source. This is typically done through the use of laboratory techniques such as molecular cloning, in which fragments of DNA are inserted into vectors (such as plasmids or viruses) and then introduced into a host organism where they can replicate and produce many copies of the recombinant DNA molecule.

Recombinant DNA technology has numerous applications in research, medicine, and industry, including the production of recombinant proteins for use as therapeutics, the creation of genetically modified organisms (GMOs) for agricultural or industrial purposes, and the development of new tools for genetic analysis and manipulation.

It's important to note that while recombinant DNA technology has many potential benefits, it also raises ethical and safety concerns, and its use is subject to regulation and oversight in many countries.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

A multigene family is a group of genetically related genes that share a common ancestry and have similar sequences or structures. These genes are arranged in clusters on a chromosome and often encode proteins with similar functions. They can arise through various mechanisms, including gene duplication, recombination, and transposition. Multigene families play crucial roles in many biological processes, such as development, immunity, and metabolism. Examples of multigene families include the globin genes involved in oxygen transport, the immune system's major histocompatibility complex (MHC) genes, and the cytochrome P450 genes associated with drug metabolism.

Alpha 1-antitrypsin (AAT, or α1-antiproteinase, A1AP) is a protein that is primarily produced by the liver and released into the bloodstream. It belongs to a group of proteins called serine protease inhibitors, which help regulate inflammation and protect tissues from damage caused by enzymes involved in the immune response.

Alpha 1-antitrypsin is particularly important for protecting the lungs from damage caused by neutrophil elastase, an enzyme released by white blood cells called neutrophils during inflammation. In the lungs, AAT binds to and inhibits neutrophil elastase, preventing it from degrading the extracellular matrix and damaging lung tissue.

Deficiency in alpha 1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD) and liver disease. The most common cause of AAT deficiency is a genetic mutation that results in abnormal folding and accumulation of the protein within liver cells, leading to reduced levels of functional AAT in the bloodstream. This condition is called alpha 1-antitrypsin deficiency (AATD) and can be inherited in an autosomal codominant manner. Individuals with severe AATD may require augmentation therapy with intravenous infusions of purified human AAT to help prevent lung damage.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

Chromosome mapping, also known as physical mapping, is the process of determining the location and order of specific genes or genetic markers on a chromosome. This is typically done by using various laboratory techniques to identify landmarks along the chromosome, such as restriction enzyme cutting sites or patterns of DNA sequence repeats. The resulting map provides important information about the organization and structure of the genome, and can be used for a variety of purposes, including identifying the location of genes associated with genetic diseases, studying evolutionary relationships between organisms, and developing genetic markers for use in breeding or forensic applications.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

A chromosome deletion is a type of genetic abnormality that occurs when a portion of a chromosome is missing or deleted. Chromosomes are thread-like structures located in the nucleus of cells that contain our genetic material, which is organized into genes.

Chromosome deletions can occur spontaneously during the formation of reproductive cells (eggs or sperm) or can be inherited from a parent. They can affect any chromosome and can vary in size, from a small segment to a large portion of the chromosome.

The severity of the symptoms associated with a chromosome deletion depends on the size and location of the deleted segment. In some cases, the deletion may be so small that it does not cause any noticeable symptoms. However, larger deletions can lead to developmental delays, intellectual disabilities, physical abnormalities, and various medical conditions.

Chromosome deletions are typically detected through a genetic test called karyotyping, which involves analyzing the number and structure of an individual's chromosomes. Other more precise tests, such as fluorescence in situ hybridization (FISH) or chromosomal microarray analysis (CMA), may also be used to confirm the diagnosis and identify the specific location and size of the deletion.

Genetic linkage is the phenomenon where two or more genetic loci (locations on a chromosome) tend to be inherited together because they are close to each other on the same chromosome. This occurs during the process of sexual reproduction, where homologous chromosomes pair up and exchange genetic material through a process called crossing over.

The closer two loci are to each other on a chromosome, the lower the probability that they will be separated by a crossover event. As a result, they are more likely to be inherited together and are said to be linked. The degree of linkage between two loci can be measured by their recombination frequency, which is the percentage of meiotic events in which a crossover occurs between them.

Linkage analysis is an important tool in genetic research, as it allows researchers to identify and map genes that are associated with specific traits or diseases. By analyzing patterns of linkage between markers (identifiable DNA sequences) and phenotypes (observable traits), researchers can infer the location of genes that contribute to those traits or diseases on chromosomes.

"Terminator regions" is a term used in molecular biology and genetics to describe specific sequences within DNA that control the termination of transcription, which is the process of creating an RNA copy of a sequence of DNA. These regions are also sometimes referred to as "transcription termination sites."

In the context of genetic terminators, the term "terminator" refers to the sequence of nucleotides that signals the end of the gene and the beginning of the termination process. The terminator region typically contains a specific sequence of nucleotides that recruits proteins called termination factors, which help to disrupt the transcription bubble and release the newly synthesized RNA molecule from the DNA template.

It's important to note that there are different types of terminators in genetics, including "Rho-dependent" and "Rho-independent" terminators, which differ in their mechanisms for terminating transcription. Rho-dependent terminators rely on the action of a protein called Rho, while Rho-independent terminators form a stable hairpin structure that causes the transcription machinery to stall and release the RNA.

In summary, "Terminator regions" in genetics are specific sequences within DNA that control the termination of transcription by signaling the end of the gene and recruiting proteins or forming structures that disrupt the transcription bubble and release the newly synthesized RNA molecule.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

Adrenergic receptors are a type of G protein-coupled receptor that bind and respond to catecholamines, such as epinephrine (adrenaline) and norepinephrine (noradrenaline). Alpha adrenergic receptors (α-ARs) are a subtype of adrenergic receptors that are classified into two main categories: α1-ARs and α2-ARs.

The activation of α1-ARs leads to the activation of phospholipase C, which results in an increase in intracellular calcium levels and the activation of various signaling pathways that mediate diverse physiological responses such as vasoconstriction, smooth muscle contraction, and cell proliferation.

On the other hand, α2-ARs are primarily located on presynaptic nerve terminals where they function to inhibit the release of neurotransmitters, including norepinephrine. The activation of α2-ARs also leads to the inhibition of adenylyl cyclase and a decrease in intracellular cAMP levels, which can mediate various physiological responses such as sedation, analgesia, and hypotension.

Overall, α-ARs play important roles in regulating various physiological functions, including cardiovascular function, mood, and cognition, and are also involved in the pathophysiology of several diseases, such as hypertension, heart failure, and neurodegenerative disorders.

Erythroblastic Leukemia, Acute (also known as Acute Erythroid Leukemia or AEL) is a subtype of acute myeloid leukemia (AML), which is a type of cancer affecting the blood and bone marrow. In this condition, there is an overproduction of erythroblasts (immature red blood cells) in the bone marrow, leading to their accumulation and interference with normal blood cell production. This results in a decrease in the number of functional red blood cells, white blood cells, and platelets in the body. Symptoms may include fatigue, weakness, frequent infections, and easy bruising or bleeding. AEL is typically treated with chemotherapy and sometimes requires stem cell transplantation.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the body's response to low oxygen levels, also known as hypoxia. HIF-1 is a heterodimeric protein composed of two subunits: an alpha subunit (HIF-1α) and a beta subunit (HIF-1β).

The alpha subunit, HIF-1α, is the regulatory subunit that is subject to oxygen-dependent degradation. Under normal oxygen conditions (normoxia), HIF-1α is constantly produced in the cell but is rapidly degraded by proteasomes due to hydroxylation of specific proline residues by prolyl hydroxylase domain-containing proteins (PHDs). This hydroxylation reaction requires oxygen as a substrate, and under hypoxic conditions, the activity of PHDs is inhibited, leading to the stabilization and accumulation of HIF-1α.

Once stabilized, HIF-1α translocates to the nucleus, where it heterodimerizes with HIF-1β and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes. This binding results in the activation of gene transcription programs that promote cellular adaptation to low oxygen levels. These adaptive responses include increased erythropoiesis, angiogenesis, glucose metabolism, and pH regulation, among others.

Therefore, HIF-1α is a critical regulator of the body's response to hypoxia, and its dysregulation has been implicated in various pathological conditions, including cancer, cardiovascular disease, and neurodegenerative disorders.

Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:

1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.

Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.

Hemoglobin (Hb or Hgb) is the main oxygen-carrying protein in the red blood cells, which are responsible for delivering oxygen throughout the body. It is a complex molecule made up of four globin proteins and four heme groups. Each heme group contains an iron atom that binds to one molecule of oxygen. Hemoglobin plays a crucial role in the transport of oxygen from the lungs to the body's tissues, and also helps to carry carbon dioxide back to the lungs for exhalation.

There are several types of hemoglobin present in the human body, including:

* Hemoglobin A (HbA): This is the most common type of hemoglobin, making up about 95-98% of total hemoglobin in adults. It consists of two alpha and two beta globin chains.
* Hemoglobin A2 (HbA2): This makes up about 1.5-3.5% of total hemoglobin in adults. It consists of two alpha and two delta globin chains.
* Hemoglobin F (HbF): This is the main type of hemoglobin present in fetal life, but it persists at low levels in adults. It consists of two alpha and two gamma globin chains.
* Hemoglobin S (HbS): This is an abnormal form of hemoglobin that can cause sickle cell disease when it occurs in the homozygous state (i.e., both copies of the gene are affected). It results from a single amino acid substitution in the beta globin chain.
* Hemoglobin C (HbC): This is another abnormal form of hemoglobin that can cause mild to moderate hemolytic anemia when it occurs in the homozygous state. It results from a different single amino acid substitution in the beta globin chain than HbS.

Abnormal forms of hemoglobin, such as HbS and HbC, can lead to various clinical disorders, including sickle cell disease, thalassemia, and other hemoglobinopathies.

Restriction mapping is a technique used in molecular biology to identify the location and arrangement of specific restriction endonuclease recognition sites within a DNA molecule. Restriction endonucleases are enzymes that cut double-stranded DNA at specific sequences, producing fragments of various lengths. By digesting the DNA with different combinations of these enzymes and analyzing the resulting fragment sizes through techniques such as agarose gel electrophoresis, researchers can generate a restriction map - a visual representation of the locations and distances between recognition sites on the DNA molecule. This information is crucial for various applications, including cloning, genome analysis, and genetic engineering.

The alpha7 nicotinic acetylcholine receptor (α7nAChR) is a type of cholinergic receptor found in the nervous system that is activated by the neurotransmitter acetylcholine. It is a ligand-gated ion channel that is widely distributed throughout the central and peripheral nervous systems, including in the hippocampus, cortex, thalamus, and autonomic ganglia.

The α7nAChR is composed of five subunits arranged around a central pore, and it has a high permeability to calcium ions (Ca2+). When acetylcholine binds to the receptor, it triggers a conformational change that opens the ion channel, allowing Ca2+ to flow into the cell. This influx of Ca2+ can activate various intracellular signaling pathways and have excitatory or inhibitory effects on neuronal activity, depending on the location and function of the receptor.

The α7nAChR has been implicated in a variety of physiological processes, including learning and memory, attention, sensory perception, and motor control. It has also been studied as a potential therapeutic target for various neurological and psychiatric disorders, such as Alzheimer's disease, schizophrenia, and pain.

A Locus Control Region (LCR) is a term used in molecular biology to describe a specific type of cis-acting DNA regulatory element that controls the expression of genes located within a genetic locus. These regions are characterized by their ability to enhance or increase the transcription of genes, particularly when they are located at a distance from the gene itself.

LCRs typically contain multiple binding sites for various transcription factors and other regulatory proteins, which work together to modulate the expression of the associated genes. They are often found in clusters near the genes they regulate, and can have a profound impact on the level, timing, and specificity of gene expression.

In the context of human genetics, LCRs have been identified as important regulators of gene expression in a number of different contexts, including development, differentiation, and disease. For example, mutations or variations in LCRs have been linked to several genetic disorders, including certain forms of cancer and hemoglobinopathies such as sickle cell anemia.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Hemin is defined as the iron(III) complex of protoporphyrin IX, which is a porphyrin derivative. It is a naturally occurring substance that is involved in various biological processes, most notably in the form of heme, which is a component of hemoglobin and other hemoproteins. Hemin is also used in medical research and therapy, such as in the treatment of methemoglobinemia and lead poisoning.

Integrin α3β1 is a type of cell surface receptor that is widely expressed in various tissues, including epithelial and endothelial cells. It is composed of two subunits, α3 and β1, which form a heterodimeric complex that plays a crucial role in cell-matrix adhesion and signaling.

Integrin α3β1 binds to several extracellular matrix proteins, such as laminin, fibronectin, and collagen IV, and mediates various cellular functions, including cell migration, proliferation, differentiation, and survival. It also participates in intracellular signaling pathways that regulate cell behavior and tissue homeostasis.

Mutations in the genes encoding integrin α3β1 have been associated with several human diseases, including blistering skin disorders, kidney disease, and cancer. Therefore, understanding the structure, function, and regulation of integrin α3β1 is essential for developing new therapeutic strategies to treat these conditions.

Integrin α4 (also known as CD49d or ITGA4) is a subunit of integrin proteins, which are heterodimeric transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions. Integrin α4 typically pairs with β1 (CD29 or ITGB1) or β7 (ITGB7) subunits to form integrins α4β1 and α4β7, respectively.

Integrin α4β1, also known as very late antigen-4 (VLA-4), is widely expressed on various hematopoietic cells, including lymphocytes, monocytes, eosinophils, and basophils. It plays crucial roles in the adhesion, migration, and homing of these cells to secondary lymphoid organs, as well as in the recruitment of immune cells to inflammatory sites. Integrin α4β1 binds to its ligands, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin, via the arginine-glycine-aspartic acid (RGD) motif.

Integrin α4β7, on the other hand, is primarily expressed on gut-homing lymphocytes and interacts with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a protein mainly found in the high endothelial venules of intestinal Peyer's patches and mesenteric lymph nodes. This interaction facilitates the trafficking of immune cells to the gastrointestinal tract, where they participate in immune responses against pathogens and maintain gut homeostasis.

In summary, Integrin α4 is a crucial subunit of integrins that mediates cell adhesion, migration, and homing to specific tissues through its interactions with various ligands. Dysregulation of integrin α4 has been implicated in several pathological conditions, including inflammatory diseases, autoimmune disorders, and cancer metastasis.

Integrin α6 (also known as CD49f) is a type of integrin, which is a heterodimeric transmembrane receptor that mediates cell-cell and cell-extracellular matrix (ECM) interactions. Integrins play crucial roles in various biological processes such as cell adhesion, migration, proliferation, differentiation, and survival.

Integrin α6 is a 130 kDa glycoprotein that pairs with integrin β1, β4 or β5 to form three distinct heterodimeric complexes: α6β1, α6β4, and α6β5. Among these, the α6β4 integrin is the most extensively studied. It specifically binds to laminins in the basement membrane and plays essential roles in maintaining epithelial tissue architecture and function.

The α6β4 integrin has a unique structure with an extended cytoplasmic domain of β4 that can interact with intracellular signaling molecules, cytoskeletal proteins, and other adhesion receptors. This interaction allows the formation of stable adhesion complexes called hemidesmosomes, which anchor epithelial cells to the basement membrane and provide mechanical stability to tissues.

Mutations in integrin α6 or its partners can lead to various human diseases, including epidermolysis bullosa, a group of inherited skin disorders characterized by fragile skin and mucous membranes that blister and tear easily.

A "gene switch" in molecular biology refers to regulatory elements that control the expression of genes, turning them on or off in response to various signals. These switches are typically made up of DNA sequences that bind to specific proteins called transcription factors. When these transcription factors bind to the gene switch, they can either activate or repress the transcription of the associated gene into messenger RNA (mRNA), which is then translated into protein.

Gene switches are critical for normal development and physiology, as they allow cells to respond to changes in their environment and to coordinate their activities with other cells. They also play a key role in diseases such as cancer, where abnormal gene expression can contribute to the growth and progression of tumors. By understanding how gene switches work, researchers hope to develop new strategies for treating or preventing diseases caused by abnormal gene expression.

Integrin α5β1, also known as very late antigen-5 (VLA-5) or fibronectin receptor, is a heterodimeric transmembrane receptor protein composed of two subunits: α5 and β1. This integrin is widely expressed in various cell types, including endothelial cells, smooth muscle cells, and fibroblasts.

Integrin α5β1 plays a crucial role in mediating cell-matrix adhesion by binding to the arginine-glycine-aspartic acid (RGD) sequence present in the extracellular matrix protein fibronectin. The interaction between integrin α5β1 and fibronectin is essential for various biological processes, such as cell migration, proliferation, differentiation, and survival. Additionally, this integrin has been implicated in several pathological conditions, including tumor progression, angiogenesis, and fibrosis.

Erythropoiesis is the process of forming and developing red blood cells (erythrocytes) in the body. It occurs in the bone marrow and is regulated by the hormone erythropoietin (EPO), which is produced by the kidneys. Erythropoiesis involves the differentiation and maturation of immature red blood cell precursors called erythroblasts into mature red blood cells, which are responsible for carrying oxygen to the body's tissues. Disorders that affect erythropoiesis can lead to anemia or other blood-related conditions.

Hemoglobinopathies are a group of genetic disorders characterized by structural or functional abnormalities of the hemoglobin molecule in red blood cells. Hemoglobin is a complex protein that plays a crucial role in carrying oxygen throughout the body. The two most common types of hemoglobinopathies are sickle cell disease and thalassemia.

In sickle cell disease, a single mutation in the beta-globin gene results in the production of an abnormal form of hemoglobin called hemoglobin S (HbS). When deoxygenated, HbS molecules tend to aggregate and form long polymers, causing the red blood cells to become sickle-shaped, rigid, and fragile. These abnormally shaped cells can block small blood vessels, leading to tissue damage, chronic pain, organ dysfunction, and other serious complications.

Thalassemias are a heterogeneous group of disorders caused by mutations in the genes that regulate the production of alpha- or beta-globin chains. These mutations result in reduced or absent synthesis of one or more globin chains, leading to an imbalance in hemoglobin composition and structure. This imbalance can cause premature destruction of red blood cells (hemolysis), resulting in anemia, jaundice, splenomegaly, and other symptoms.

Hemoglobinopathies are typically inherited in an autosomal recessive manner, meaning that affected individuals have two copies of the abnormal gene – one from each parent. Carriers of a single abnormal gene usually do not show any signs or symptoms of the disorder but can pass the abnormal gene on to their offspring.

Early diagnosis and appropriate management of hemoglobinopathies are essential for improving quality of life, reducing complications, and increasing survival rates. Treatment options may include blood transfusions, iron chelation therapy, antibiotics, pain management, and, in some cases, bone marrow transplantation or gene therapy.

Integrin α4β1, also known as Very Late Antigen-4 (VLA-4), is a heterodimeric transmembrane receptor protein composed of two subunits, α4 and β1. It is involved in various cellular activities such as adhesion, migration, and signaling. This integrin plays a crucial role in the immune system by mediating the interaction between leukocytes (white blood cells) and the endothelial cells that line blood vessels. The activation of Integrin α4β1 allows leukocytes to roll along and then firmly adhere to the endothelium, followed by their migration into surrounding tissues, particularly during inflammation and immune responses. Additionally, Integrin α4β1 also interacts with extracellular matrix proteins such as fibronectin and helps regulate cell survival, proliferation, and differentiation in various cell types.

Interleukin-1 alpha (IL-1α) is a member of the interleukin-1 cytokine family, which plays a crucial role in the regulation of inflamation and immune responses. IL-1α is primarily produced by activated macrophages, epithelial cells, and fibroblasts. It is a potent proinflammatory cytokine that binds to the interleukin-1 receptor (IL-1R) and activates signaling pathways leading to the expression of genes involved in inflammation, fever, and cellular activation. IL-1α is involved in various physiological processes such as hematopoiesis, bone remodeling, and response to infection or injury. Dysregulation of IL-1α has been implicated in several pathological conditions including autoimmune diseases, atherosclerosis, and cancer.

Protein biosynthesis is the process by which cells generate new proteins. It involves two major steps: transcription and translation. Transcription is the process of creating a complementary RNA copy of a sequence of DNA. This RNA copy, or messenger RNA (mRNA), carries the genetic information to the site of protein synthesis, the ribosome. During translation, the mRNA is read by transfer RNA (tRNA) molecules, which bring specific amino acids to the ribosome based on the sequence of nucleotides in the mRNA. The ribosome then links these amino acids together in the correct order to form a polypeptide chain, which may then fold into a functional protein. Protein biosynthesis is essential for the growth and maintenance of all living organisms.

Erythroid cells are a type of blood cell that develops in the bone marrow and mature into red blood cells (RBCs), also known as erythrocytes. These cells play a crucial role in the body's oxygen-carrying capacity by transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

The development of erythroid cells begins with hematopoietic stem cells, which can differentiate into various types of blood cells. Through a series of maturation stages, including proerythroblasts, basophilic erythroblasts, polychromatophilic erythroblasts, and orthochromatic erythroblasts, these cells gradually lose their nuclei and organelles to become reticulocytes. Reticulocytes are immature RBCs that still contain some residual ribosomes and are released into the bloodstream. Over time, they mature into fully functional RBCs, which have a biconcave shape and a flexible membrane that allows them to navigate through small blood vessels.

Erythroid cells are essential for maintaining adequate oxygenation of body tissues, and their production is tightly regulated by various hormones and growth factors, such as erythropoietin (EPO), which stimulates the proliferation and differentiation of erythroid progenitor cells. Abnormalities in erythroid cell development or function can lead to various blood disorders, including anemia, polycythemia, and myelodysplastic syndromes.

Integrin α2β1, also known as very late antigen-2 (VLA-2) or laminin receptor, is a heterodimeric transmembrane receptor protein composed of α2 and β1 subunits. It belongs to the integrin family of adhesion molecules that play crucial roles in cell-cell and cell-extracellular matrix (ECM) interactions.

Integrin α2β1 is widely expressed on various cell types, including fibroblasts, endothelial cells, smooth muscle cells, and some hematopoietic cells. It functions as a receptor for several ECM proteins, such as collagens (type I, II, III, and V), laminin, and fibronectin. The binding of integrin α2β1 to these ECM components mediates cell adhesion, migration, proliferation, differentiation, and survival, thereby regulating various physiological and pathological processes, such as tissue repair, angiogenesis, inflammation, and tumor progression.

In addition, integrin α2β1 has been implicated in several diseases, including fibrosis, atherosclerosis, and cancer. Therefore, targeting this integrin with therapeutic strategies may provide potential benefits for treating these conditions.

Alpha-1 adrenergic receptors (also known as α1-adrenoreceptors) are a type of G protein-coupled receptor that binds catecholamines, such as norepinephrine and epinephrine. These receptors are primarily found in the smooth muscle of various organs, including the vasculature, heart, liver, kidneys, gastrointestinal tract, and genitourinary system.

When an alpha-1 adrenergic receptor is activated by a catecholamine, it triggers a signaling cascade that leads to the activation of phospholipase C, which in turn activates protein kinase C and increases intracellular calcium levels. This ultimately results in smooth muscle contraction, increased heart rate and force of contraction, and vasoconstriction.

Alpha-1 adrenergic receptors are also found in the central nervous system, where they play a role in regulating wakefulness, attention, and anxiety. There are three subtypes of alpha-1 adrenergic receptors (α1A, α1B, and α1D), each with distinct physiological roles and pharmacological properties.

In summary, alpha-1 adrenergic receptors are a type of G protein-coupled receptor that binds catecholamines and mediates various physiological responses, including smooth muscle contraction, increased heart rate and force of contraction, vasoconstriction, and regulation of wakefulness and anxiety.

Integrin α5 (also known as CD49e) is a subunit of the heterodimeric integrin receptor called very late antigen-5 (VLA-5). Integrins are transmembrane adhesion receptors that play crucial roles in cell-cell and cell-extracellular matrix interactions. The α5β1 integrin, formed by the association of α5 and β1 subunits, specifically recognizes and binds to fibronectin, a major extracellular matrix protein. This binding event is essential for various biological processes such as cell migration, proliferation, differentiation, and survival.

In summary, Integrin alpha5 (α5) is an essential subunit of the α5β1 integrin receptor that mediates cell-fibronectin interactions and contributes to several vital cellular functions.

Integrin α1β1, also known as Very Late Antigen-1 (VLA-1) or CD49a/CD29, is a heterodimeric transmembrane receptor protein composed of α1 and β1 subunits. It belongs to the integrin family of adhesion molecules that play crucial roles in cell-cell and cell-extracellular matrix (ECM) interactions.

Integrin α1β1 is primarily expressed on various cell types, including fibroblasts, endothelial cells, smooth muscle cells, and some immune cells. This integrin binds to several ECM proteins, such as collagens (type I, II, III, IV), laminin, and fibronectin, mediating cell adhesion, migration, proliferation, differentiation, and survival. Additionally, α1β1 integrin has been implicated in various physiological and pathological processes, such as tissue repair, fibrosis, and tumor progression.

Erythroblasts are immature red blood cells that are produced in the bone marrow. They are also known as normoblasts and are a stage in the development of red blood cells, or erythrocytes. Erythroblasts are larger than mature red blood cells and have a nucleus, which is lost during the maturation process. These cells are responsible for producing hemoglobin, the protein that carries oxygen in the blood. Abnormal increases or decreases in the number of erythroblasts can be indicative of certain medical conditions, such as anemia or leukemia.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Erythrocytes, also known as red blood cells (RBCs), are the most common type of blood cell in circulating blood in mammals. They are responsible for transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

Erythrocytes are formed in the bone marrow and have a biconcave shape, which allows them to fold and bend easily as they pass through narrow blood vessels. They do not have a nucleus or mitochondria, which makes them more flexible but also limits their ability to reproduce or repair themselves.

In humans, erythrocytes are typically disc-shaped and measure about 7 micrometers in diameter. They contain the protein hemoglobin, which binds to oxygen and gives blood its red color. The lifespan of an erythrocyte is approximately 120 days, after which it is broken down in the liver and spleen.

Abnormalities in erythrocyte count or function can lead to various medical conditions, such as anemia, polycythemia, and sickle cell disease.

Alpha-2 adrenergic receptors are a type of G protein-coupled receptor that binds catecholamines, such as norepinephrine and epinephrine. These receptors are widely distributed in the central and peripheral nervous system, as well as in various organs and tissues throughout the body.

Activation of alpha-2 adrenergic receptors leads to a variety of physiological responses, including inhibition of neurotransmitter release, vasoconstriction, and reduced heart rate. These receptors play important roles in regulating blood pressure, pain perception, and various cognitive and emotional processes.

There are several subtypes of alpha-2 adrenergic receptors, including alpha-2A, alpha-2B, and alpha-2C, which may have distinct physiological functions and be targeted by different drugs. For example, certain medications used to treat hypertension or opioid withdrawal target alpha-2 adrenergic receptors to produce their therapeutic effects.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Integrin α6β1, also known as CD49f/CD29, is a heterodimeric transmembrane receptor protein composed of α6 and β1 subunits. It is widely expressed in various tissues, including epithelial cells, endothelial cells, fibroblasts, and hematopoietic cells. Integrin α6β1 plays a crucial role in cell-matrix adhesion, particularly to the laminin component of the extracellular matrix (ECM). This receptor is involved in various biological processes such as cell migration, proliferation, differentiation, and survival. Additionally, integrin α6β1 has been implicated in tumor progression, metastasis, and drug resistance in certain cancers.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

Hemoglobin A is the most common form of hemoglobin, which is the oxygen-carrying protein in red blood cells. Hemoglobin A is a tetramer composed of two alpha and two beta globin chains, each containing a heme group that binds to oxygen. It is typically measured in laboratory tests to assess for various medical conditions such as anemia or diabetes. In the context of diabetes, the measurement of hemoglobin A1c (a form of hemoglobin A that is glycated or bound to glucose) is used to monitor long-term blood sugar control.

Erythroid precursor cells, also known as erythroblasts or normoblasts, are early stage cells in the process of producing mature red blood cells (erythrocytes) in the bone marrow. These cells are derived from hematopoietic stem cells and undergo a series of maturation stages, including proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, and orthochromatic erythroblast, before becoming reticulocytes and then mature red blood cells. During this maturation process, the cells lose their nuclei and become enucleated, taking on the biconcave shape and flexible membrane that allows them to move through small blood vessels and deliver oxygen to tissues throughout the body.

Gamma-globulins are a type of globulin, which are proteins found in the blood plasma. More specifically, gamma-globulins are a class of immunoglobulins, also known as antibodies, that play a crucial role in the immune system's response to foreign substances and infectious agents.

Immunoglobulins are divided into several classes based on their structure and function. Gamma-globulins include IgG, IgA, and IgD isotypes of immunoglobulins. Among these, IgG is the most abundant type found in the blood and other body fluids, responsible for providing protection against bacterial and viral infections.

Gamma-globulins are produced by B cells, a type of white blood cell involved in the immune response. They can be measured in the blood as part of a complete blood count (CBC) or specific protein electrophoresis tests to assess immune system function or diagnose various medical conditions such as infections, inflammation, and autoimmune disorders.

Integrin α6β4 is a type of cell surface receptor that is composed of two subunits, α6 and β4. It is also known as CD49f/CD104. This integrin is primarily expressed in epithelial cells and plays important roles in cell adhesion, migration, and signal transduction.

Integrin α6β4 specifically binds to laminin-332 (also known as laminin-5), a component of the basement membrane, and forms a stable anchorage complex that links the cytoskeleton to the extracellular matrix. This interaction is critical for maintaining the integrity of epithelial tissues and regulating cell behavior during processes such as wound healing and tissue regeneration.

Mutations in the genes encoding integrin α6β4 have been associated with various human diseases, including epidermolysis bullosa, a group of inherited skin disorders characterized by fragile skin and blistering. Additionally, integrin α6β4 has been implicated in cancer progression and metastasis, as its expression is often upregulated in tumor cells and contributes to their invasive behavior.

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Integrins are a family of cell-surface receptors that play crucial roles in various biological processes, including cell adhesion, migration, and signaling. Integrin alpha chains are one of the two subunits that make up an integrin heterodimer, with the other subunit being an integrin beta chain.

Integrin alpha chains are transmembrane glycoproteins consisting of a large extracellular domain, a single transmembrane segment, and a short cytoplasmic tail. The extracellular domain contains several domains that mediate ligand binding, while the cytoplasmic tail interacts with various cytoskeletal proteins and signaling molecules to regulate intracellular signaling pathways.

There are 18 different integrin alpha chains known in humans, each of which can pair with one or more beta chains to form distinct integrin heterodimers. These heterodimers exhibit unique ligand specificities and functions, allowing them to mediate diverse cell-matrix and cell-cell interactions.

In summary, integrin alpha chains are essential subunits of integrin receptors that play crucial roles in regulating cell adhesion, migration, and signaling by mediating interactions between cells and their extracellular environment.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Integrins are a type of cell-adhesion molecule that play a crucial role in cell-cell and cell-extracellular matrix (ECM) interactions. They are heterodimeric transmembrane receptors composed of non-covalently associated α and β subunits, which form more than 24 distinct integrin heterodimers in humans.

Integrins bind to specific ligands, such as ECM proteins (e.g., collagen, fibronectin, laminin), cell surface molecules, and soluble factors, through their extracellular domains. The intracellular domains of integrins interact with the cytoskeleton and various signaling proteins, allowing them to transduce signals from the ECM into the cell (outside-in signaling) and vice versa (inside-out signaling).

These molecular interactions are essential for numerous biological processes, including cell adhesion, migration, proliferation, differentiation, survival, and angiogenesis. Dysregulation of integrin function has been implicated in various pathological conditions, such as cancer, fibrosis, inflammation, and autoimmune diseases.

Integrin α1 (also known as ITGA1 or CD49a) is a subunit of a heterodimeric integrin receptor, specifically the collagen receptor α1β1. Integrins are transmembrane proteins that play crucial roles in cell-cell and cell-extracellular matrix (ECM) adhesion, signaling, migration, proliferation, and differentiation. The α1β1 integrin binds to various collagen types, such as collagens I, II, III, and V, and mediates cellular responses upon binding to these ECM components.

The gene encoding Integrin α1 is located on chromosome 5 (5q31) in humans. Mutations in the ITGA1 gene can lead to various diseases, including leukocyte adhesion deficiency type II and some forms of epidermolysis bullosa.

Alpha rhythm is a type of brain wave that is typically observed in the electroencephalogram (EEG) of normal, awake individuals when they have their eyes closed. It is characterized by sinusoidal waves with a frequency range of 8-13 Hz and is most prominent over the occipital region of the head, which is located at the back of the skull above the brain's visual cortex.

Alpha rhythm is typically associated with relaxed wakefulness, and its presence may indicate that an individual is awake but not engaged in any mentally demanding tasks. It can be blocked or suppressed by various stimuli, such as opening one's eyes, hearing a loud noise, or engaging in mental activity.

Disruptions in alpha rhythm have been observed in various neurological and psychiatric conditions, including epilepsy, dementia, depression, and anxiety disorders. However, more research is needed to fully understand the clinical significance of these abnormalities.

Macromolecular substances, also known as macromolecules, are large, complex molecules made up of repeating subunits called monomers. These substances are formed through polymerization, a process in which many small molecules combine to form a larger one. Macromolecular substances can be naturally occurring, such as proteins, DNA, and carbohydrates, or synthetic, such as plastics and synthetic fibers.

In the context of medicine, macromolecular substances are often used in the development of drugs and medical devices. For example, some drugs are designed to bind to specific macromolecules in the body, such as proteins or DNA, in order to alter their function and produce a therapeutic effect. Additionally, macromolecular substances may be used in the creation of medical implants, such as artificial joints and heart valves, due to their strength and durability.

It is important for healthcare professionals to have an understanding of macromolecular substances and how they function in the body, as this knowledge can inform the development and use of medical treatments.

Integrin α3 (also known as ITGA3) is a subunit of a type of cell-surface receptor called an integrin. Integrins are involved in cell-cell and cell-extracellular matrix (ECM) interactions, and play important roles in various biological processes such as cell adhesion, migration, and survival.

Integrin α3 combines with the β1 subunit to form the integrin heterodimer α3β1, which is widely expressed in many tissues including epithelial cells, endothelial cells, and fibroblasts. Integrin α3β1 binds to various ECM proteins such as laminin-5, fibronectin, and collagen IV, and mediates cell adhesion and migration on these substrates.

Mutations in the ITGA3 gene have been associated with several human genetic disorders, including epidermolysis bullosa with pyloric atresia (EB-PA), a severe form of inherited skin fragility disorder, and Adams-Oliver syndrome, a rare genetic disorder characterized by scalp defects and limb abnormalities.

Alpha 1-Antitrypsin (AAT) deficiency is a genetic disorder that results from insufficient levels of the protective protein AAT in the blood and lungs. This protein is produced by the liver and helps to protect the lungs from damage caused by inflammation and the action of enzymes, such as neutrophil elastase, that are released during the immune response.

In people with AAT deficiency, the lack of adequate AAT levels leads to an uncontrolled increase in neutrophil elastase activity, which can cause damage to lung tissue and result in emphysema, a condition characterized by shortness of breath, coughing, and wheezing. Additionally, some individuals with AAT deficiency may develop liver disease due to the accumulation of abnormal AAT proteins in liver cells.

There are different variants or genotypes associated with AAT deficiency, with the most common and severe form being the PiZZ genotype. This variant is caused by mutations in the SERPINA1 gene, which encodes for the AAT protein. Individuals who inherit two copies of this mutated gene (one from each parent) will have very low levels of AAT in their blood and are at increased risk of developing emphysema and liver disease.

Diagnosis of AAT deficiency typically involves measuring AAT levels in the blood and performing genetic testing to identify specific variants of the SERPINA1 gene. Treatment may include lifestyle modifications, such as smoking cessation, bronchodilators, and corticosteroids to manage lung symptoms, as well as augmentation therapy with intravenous infusions of AAT protein to help slow disease progression in individuals with severe deficiency. Liver transplantation may be considered for those with advanced liver disease.

Heme is not a medical term per se, but it is a term used in the field of medicine and biology. Heme is a prosthetic group found in hemoproteins, which are proteins that contain a heme iron complex. This complex plays a crucial role in various biological processes, including oxygen transport (in hemoglobin), electron transfer (in cytochromes), and chemical catalysis (in peroxidases and catalases).

The heme group consists of an organic component called a porphyrin ring, which binds to a central iron atom. The iron atom can bind or release electrons, making it essential for redox reactions in the body. Heme is also vital for the formation of hemoglobin and myoglobin, proteins responsible for oxygen transport and storage in the blood and muscles, respectively.

In summary, heme is a complex organic-inorganic structure that plays a critical role in several biological processes, particularly in electron transfer and oxygen transport.

Truncated hemoglobins are a group of hemoglobin variants that lack the normal C-terminal extension of the beta-globin chain. They were first identified in organisms living in extreme environments, such as bacteria found in deep-sea hydrothermal vents and in animals adapted to high-altitude hypoxia. These hemoglobins have unique structural and functional properties that allow them to function efficiently under low oxygen concentrations.

Truncated hemoglobins are characterized by the absence of the last 1-3 amino acids at the C-terminus of the beta-globin chain, which results in a more compact structure compared to normal hemoglobin. This structural difference leads to altered oxygen binding properties and increased stability under extreme conditions.

Truncated hemoglobins have been studied for their potential applications in biotechnology and medicine, particularly in the development of new strategies for the treatment of hypoxia-related disorders such as ischemia, stroke, and cancer. However, further research is needed to fully understand their mechanisms of action and therapeutic potential.

Nicotinic receptors are a type of ligand-gated ion channel receptor that are activated by the neurotransmitter acetylcholine and the alkaloid nicotine. They are widely distributed throughout the nervous system and play important roles in various physiological processes, including neuronal excitability, neurotransmitter release, and cognitive functions such as learning and memory. Nicotinic receptors are composed of five subunits that form a ion channel pore, which opens to allow the flow of cations (positively charged ions) when the receptor is activated by acetylcholine or nicotine. There are several subtypes of nicotinic receptors, which differ in their subunit composition and functional properties. These receptors have been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.

Adrenergic alpha-agonists are a type of medication that binds to and activates adrenergic alpha receptors, which are found in the nervous system and other tissues throughout the body. These receptors are activated naturally by chemicals called catecholamines, such as norepinephrine and epinephrine (also known as adrenaline), that are released in response to stress or excitement.

When adrenergic alpha-agonists bind to these receptors, they mimic the effects of catecholamines and cause various physiological responses, such as vasoconstriction (constriction of blood vessels), increased heart rate and force of heart contractions, and relaxation of smooth muscle in the airways.

Adrenergic alpha-agonists are used to treat a variety of medical conditions, including hypertension (high blood pressure), glaucoma, nasal congestion, and attention deficit hyperactivity disorder (ADHD). Examples of adrenergic alpha-agonists include phenylephrine, clonidine, and guanfacine.

It's important to note that adrenergic alpha-agonists can have both beneficial and harmful effects, depending on the specific medication, dosage, and individual patient factors. Therefore, they should only be used under the guidance of a healthcare professional.

The NF-E2 (Nuclear Factor, Erythroid-derived 2) transcription factor is a heterodimeric protein that plays a crucial role in the regulation of gene expression. It is composed of two subunits: p18 and p45. The p45 subunit, also known as NFE2L2 or GABPalpha, is a member of the basic region-leucine zipper (bZIP) family of transcription factors.

The p45 subunit forms a complex with the p18 subunit, and this complex binds to specific DNA sequences called antioxidant response elements (AREs) or electrophile response elements (EpREs), which are present in the promoter regions of various genes involved in cellular defense against oxidative stress and xenobiotic metabolism.

The p45 subunit is responsible for recognizing and binding to the DNA sequence, while the p18 subunit stabilizes the complex and enhances its DNA-binding affinity. Together, they regulate the expression of genes involved in heme biosynthesis, cytochrome P450 activity, antioxidant defense, and other cellular processes.

Mutations in the NFE2L2 gene, which encodes the p45 subunit, have been associated with various diseases, including chronic obstructive pulmonary disease (COPD), neurodegenerative disorders, and cancer.

PPAR-alpha (Peroxisome Proliferator-Activated Receptor alpha) is a type of nuclear receptor protein that functions as a transcription factor, regulating the expression of specific genes involved in lipid metabolism. It plays a crucial role in the breakdown of fatty acids and the synthesis of high-density lipoproteins (HDL or "good" cholesterol) in the liver. PPAR-alpha activation also has anti-inflammatory effects, making it a potential therapeutic target for metabolic disorders such as diabetes, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD).

Dinoprost is a synthetic form of prostaglandin F2α, which is a naturally occurring hormone-like substance in the body. It is used in veterinary medicine as a uterotonic agent to induce labor and abortion in various animals such as cows and pigs. In human medicine, it may be used off-label for similar purposes, but its use must be under the close supervision of a healthcare provider due to potential side effects and risks.

It is important to note that Dinoprost is not approved by the FDA for use in humans, and its availability may vary depending on the country or region. Always consult with a licensed healthcare professional before using any medication, including Dinoprost.

Adrenergic alpha-antagonists, also known as alpha-blockers, are a class of medications that block the effects of adrenaline and noradrenaline at alpha-adrenergic receptors. These receptors are found in various tissues throughout the body, including the smooth muscle of blood vessels, the heart, the genitourinary system, and the eyes.

When alpha-blockers bind to these receptors, they prevent the activation of the sympathetic nervous system, which is responsible for the "fight or flight" response. This results in a relaxation of the smooth muscle, leading to vasodilation (widening of blood vessels), decreased blood pressure, and increased blood flow.

Alpha-blockers are used to treat various medical conditions, such as hypertension (high blood pressure), benign prostatic hyperplasia (enlarged prostate), pheochromocytoma (a rare tumor of the adrenal gland), and certain types of glaucoma.

Examples of alpha-blockers include doxazosin, prazosin, terazosin, and tamsulosin. Side effects of alpha-blockers may include dizziness, lightheadedness, headache, weakness, and orthostatic hypotension (a sudden drop in blood pressure upon standing).

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Erythroid-specific DNA-binding factors are transcription factors that bind to specific sequences of DNA and help regulate the expression of genes that are involved in the development and differentiation of erythroid cells, which are cells that mature to become red blood cells. These transcription factors play a crucial role in the production of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. Examples of erythroid-specific DNA-binding factors include GATA-1 and KLF1.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Nuclear factor, erythroid-derived 2 (NFE2), also known as NF-E2 transcription factor, is a protein that plays a crucial role in the regulation of gene expression. It belongs to the cap'n'collar (CNC) subfamily of basic region-leucine zipper (bZIP) transcription factors.

NFE2 forms a heterodimer with small Maf proteins and binds to antioxidant response elements (AREs) in the promoter regions of target genes. These target genes are often involved in cellular defense against oxidative stress, electrophiles, and inflammation. NFE2 regulates the expression of various enzymes and proteins that protect cells from damage caused by reactive oxygen species (ROS) and other harmful substances.

Mutations in the NFE2 gene have been associated with several diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and certain types of cancer. Proper regulation of NFE2 is essential for maintaining cellular homeostasis and preventing the development of various pathological conditions.

Dimethyl Sulfoxide (DMSO) is an organosulfur compound with the formula (CH3)2SO. It is a polar aprotic solvent, which means it can dissolve both polar and nonpolar compounds. DMSO has a wide range of uses in industry and in laboratory research, including as a cryoprotectant, a solvent for pharmaceuticals, and a penetration enhancer in topical formulations.

In medicine, DMSO is used as a topical analgesic and anti-inflammatory agent. It works by increasing the flow of blood and other fluids to the site of application, which can help to reduce pain and inflammation. DMSO is also believed to have antioxidant properties, which may contribute to its therapeutic effects.

It's important to note that while DMSO has been studied for various medical uses, its effectiveness for many conditions is not well established, and it can have side effects, including skin irritation and a garlic-like taste or odor in the mouth after application. It should be used under the supervision of a healthcare provider.

Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.

The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Hepatocyte Nuclear Factor 1-alpha (HNF1A) is a transcription factor that plays a crucial role in the development and function of the liver. It belongs to the family of winged helix transcription factors and is primarily expressed in the hepatocytes, which are the major cell type in the liver.

HNF1A regulates the expression of various genes involved in glucose and lipid metabolism, bile acid synthesis, and drug metabolism. Mutations in the HNF1A gene have been associated with maturity-onset diabetes of the young (MODY), a form of diabetes that is typically inherited in an autosomal dominant manner and often diagnosed in early adulthood. These mutations can lead to impaired insulin secretion and decreased glucose tolerance, resulting in the development of diabetes.

In addition to its role in diabetes, HNF1A has also been implicated in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Dysregulation of HNF1A has been shown to contribute to the development and progression of these conditions by altering the expression of genes involved in lipid metabolism, inflammation, and fibrosis.

"A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. Expression of all of ... The human β-globin locus is composed of five genes located on a short region of chromosome 11, responsible for the creation of ... The order of the genes in the beta-globin cluster is: 5' - epsilon - gamma-G - gamma-A - delta - beta - 3'. The arrangement of ...
Since the globin fold contains only helices, it is classified as an all-alpha protein fold. The globin fold is found in its ... Globin superfamily members share a common three-dimensional fold. This 'globin fold' typically consists of eight alpha helices ... Globin E: a globin responsible for storing and delivering oxygen to the retina in birds Globin-coupled sensors: chimeric, with ... Eight globins are known to occur in vertebrates: androglobin (Adgb), cytoglobin (Cygb), globin E (GbE, from bird eye), globin X ...
I. Helical regions of human alpha and beta globins". Biochemical and Biophysical Research Communications. 97 (3): 868-874. doi: ...
... while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene ... Zeta-globin is an alpha-like hemoglobin. The zeta-globin polypeptide is synthesized in the yolk sac of the early embryo, ... Orkin SH, Michelson A (July 1980). "Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia". Nature. ... The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta1 - 3'. GRCh38: Ensembl release ...
August 2005). "A newly discovered human alpha-globin gene". Blood. 106 (4): 1466-72. doi:10.1182/blood-2005-03-0948. PMC ... The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta1 - 3'. Higgs DR, Vickers MA, ... Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (April 1989). "A review of the molecular genetics of the human alpha-globin ... islands in the human alpha globin complex: association with non-functional pseudogenes and presence within the 3' portion of ...
... alpha 2 also known as HBA2 is a gene that in humans codes for the alpha globin chain of hemoglobin. The human alpha globin gene ... Voon HP, Vadolas J (Dec 2008). "Controlling alpha-globin: a review of alpha-globin expression and its impact on beta- ... Ribeiro DM, Sonati MF (2008). "Regulation of human alpha-globin gene expression and alpha-thalassemia". Genetics and Molecular ... Alpha-thalassemias most commonly result from deletions of any of the four alpha alleles, although some alpha thalassemias have ...
... with exactly the same alpha and beta globin protein chains. Human and gorilla hemoglobin differ in one amino acid in both alpha ... Each protein chain arranges into a set of alpha-helix structural segments connected together in a globin fold arrangement. Such ... Alpha 1 and alpha 2 subunits are respectively coded by genes HBA1 and HBA2 close together on chromosome 16, while the beta ... 2009). "Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells". Proceedings of ...
Alpha-globin transcription factor CP2 is a protein that in humans is encoded by the TFCP2 gene. TFCP2 is also called Late SV40 ... Lim LC, Swendeman SL, Sheffery M (Feb 1992). "Molecular cloning of the alpha-globin transcription factor CP2". Molecular and ... and development expression of the alpha-globin transcription factor CP2". The Journal of Biological Chemistry. 269 (15): 11663- ... Zhou W, Clouston DR, Wang X, Cerruti L, Cunningham JM, Jane SM (Oct 2000). "Induction of human fetal globin gene expression by ...
Kiledjian M, Wang X, Liebhaber SA (1995). "Identification of two KH domain proteins in the alpha-globin mRNP stability complex ... Proteins of this subfamily, also referred to as alpha-CPs, bind to RNA with a specificity for C-rich pyrimidine regions. Alpha- ...
... suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin ... as a component of the alpha-globin mRNA stability complex". Mol. Cell. Biol. 17 (8): 4870-6. doi:10.1128/MCB.17.8.4870. PMC ... "Identification of two KH domain proteins in the alpha-globin mRNP stability complex". EMBO J. 14 (17): 4357-64. doi:10.1002/j. ...
Proudfoot NJ, Maniatis T (1980). "The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene ... Orkin SH, Michelson A (1980). "Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia". Nature. 286 ( ... Safaya S, Rieder RF (1988). "Dysfunctional alpha-globin gene in hemoglobin H disease in blacks. A dinucleotide deletion ... Hemoglobin, alpha pseudogene 1, also known as HBAP1, is a human gene. GRCh38: Ensembl release 89: ENSG00000225323 - Ensembl, ...
For example, ATRX mutations affect the expression of alpha-globin gene cluster, causing alpha-thalassemia." ATRX interacts with ... Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked intellectual disability syndrome, ... GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia X-Linked Mental Retardation Syndrome; ATRX Syndrome; Alpha Thalassemia/ ... This group is important for regulating the transcription of the alpha genes. If ATR-X is suspected based on symptoms, diagnosis ...
In 1980, a study was conducted on the 3' UTR of the duplicated human alpha-globin genes. The untranslated region is seen in ... Michelson, A. M.; Orkin, S. H. (1980-11-01). "The 3' untranslated regions of the duplicated human alpha-globin genes are ... In 1978, the 5' UTR of the human gamma-globin mRNA was fully sequenced. ... untranslated region of human gamma-globin mRNA". Nucleic Acids Research. 5 (10): 3515-3522. doi:10.1093/nar/5.10.3515. ISSN ...
Globin synthesis defect sickle cell disease Alpha-thalassemia, e.g. HbH disease Systemic conditions Sepsis Arteriovenous ... The breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance ... alpha), 20(beta)-diol in maternal milk that inhibits glucuronide formation in vitro". J Clin Invest. 43 (11): 2037-47. doi: ... alpha 1-antitrypsin deficiency, and other pediatric liver diseases should be considered. The evaluation for these will include ...
Globin superfamily Members share an 8-alpha helix globular globin fold. Immunoglobulin superfamily Members share a sandwich- ...
... defining the centromeric boundary of the human alpha-globin domain". Genomics. 71 (3): 307-14. doi:10.1006/geno.2000.6394. PMID ...
"Regulation of Globin Gene Expression". {{cite journal}}: Cite journal requires ,journal= (help) "World Renowned Geneticist ... Smaglik, Paul (2007-11-28). "Richard Myers, director of Hudson-Alpha Institute for Biotechnology, Huntsville, Alabama". Nature ... His team sought to understand globin gene expression, studying both cis- and trans-acting components that regulate ... Smaglik, Paul (2007-11-28). "Richard Myers, director of Hudson-Alpha Institute for Biotechnology, Huntsville, Alabama". Nature ...
... two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions). Deletion of ... it begins to produce alpha-globins at weeks 5-6 of development. When both of the HBA1 and HBA2 genes which code for alpha ... These gamma globins bind to form hemoglobin Barts. It is produced in the disease alpha-thalassemia and in the most severe of ... Table 1: α represents the presence of α-globin gene and- represents the deletion of α-globin gene. The chance of a fetus ...
There are two subunits that make up the hemoglobin protein: beta-globins and alpha-globins. Beta-hemoglobin is created from the ... The β-globin gene is found on the short arm of chromosome 11. The association of two wild-type α-globin subunits with two ... The single nucleotide change in the beta-globin means that even the smallest of exertions on the part of the carrier results in ... Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the hydrophilic amino acid ...
Ribeiro, Daniela M.; Figueiredo, Maria S.; Costa, Fernando F.; Sonati, Maria F. (2003). "Haplotypes of alpha-globin gene ...
Differences in the regulated expression of cloned human alpha globin and beta globin genes introduced into MEL cells: the role ... Basis for regulating the expression of human alpha- and beta-globin genes. Discovery of a family of vertebrate genes encoding ... Transcriptional regulation of globin gene expression in the human erythroid cell line K562 », Science, (1983), 220, p. 1281- ... where he studied the molecular basis for the regulation of globin gene expression. In 1984, he joined the European Molecular ...
"A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... Mutations in the delta-globin gene are associated with Delta-thalassemia. Hemoglobin Human β-globin locus Thalassemia GRCh38: ... Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5' - epsilon - gamma-G - ... Two alpha chains plus two delta chains constitute HbA2, which with HbF comprises the remaining 3% of adult hemoglobin. ...
... β-globin, haemoglobin beta, hemoglobin beta) is a globin protein, coded for by the HBB gene, which along with alpha globin (HBA ... Expression of beta globin and the neighbouring globins in the β-globin locus is controlled by single locus control region (LCR ... Hemoglobin subunit alpha Human β-globin locus GRCh38: Ensembl release 89: ENSG00000244734 - Ensembl, May 2017 GRCm38: Ensembl ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ...
... ; Morris Goodman; G. William Moore (1972). "Descent of Mammalian Alpha Globin Chain Sequences Investigated by the ...
"A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... The gamma globin genes (HBG1 and HBG2, this gene) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma ... The order of the genes in the beta-globin cluster is: 5' - epsilon - gamma-G - gamma-A - delta - beta - 3'. GRCh38: Ensembl ... chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at ...
2002). "Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein". J. Biol. Chem. ... 2007). "Reversible hexacoordination of alpha-hemoglobin-stabilizing protein (AHSP)/alpha-hemoglobin Versus pressure. Evidence ... Alpha-hemoglobin-stabilizing protein is a protein that in humans is encoded by the ERAF gene. GRCh38: Ensembl release 89: ... 2006). "Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia". Ann. N. Y. Acad. Sci. 1054 ...
... an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form ... Hemoglobin Human β-globin locus Hemoglobin alpha chains (two genes, same sequence): HBA1 HBA2 GRCh38: Ensembl release 89: ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains ...
Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order ... "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... Theta-globin mRNA is found in human fetal erythroid tissue but not in adult erythroid or other nonerythroid tissue. The theta-1 ... Gonzalez-Redondo JM, Han IS, Gu YC, Huisman TH (1988). "Nucleotide sequence of the human theta 1-globin gene". Biochem. Genet. ...
These hubs were discovered during observation of activated alpha- and beta-globin loci. ACHs are formed through extensive DNA ... "Looping and interaction between hypersensitive sites in the active beta-globin locus". Molecular Cell. 10 (6): 1453-65. doi: ...
It consists of a five-prime cap; a five prime untranslated region derived from the sequence of human alpha globin; a signal ... In this case, a person who received two doses of the Pfizer vaccine was 93.7% less likely to contract the alpha variant and ... During this period, according to Nextstrain, the dominant variant in Israel was lineage B.1.1.50 and the Alpha variant was ... Notably, effectiveness after one dose of the Pfizer vaccine was 48.7% against alpha and 30.7% against delta, similar to ...
"A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081-104. doi:10.1182/blood.V73.5. ... This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. Expression of all of ... The human β-globin locus is composed of five genes located on a short region of chromosome 11, responsible for the creation of ... The order of the genes in the beta-globin cluster is: 5 - epsilon - gamma-G - gamma-A - delta - beta - 3. The arrangement of ...
Supplementary test information for Beta Globin (HBB) Sequencing such as test interpretation, additional tests to consider, and ... Major adult Hb (HbA) is composed of two β-globin chains and two alpha (α)-globin chains. ... Typically, adults have two functional β-globin genes (HBB) and four functional α-globin genes (two copies each of HBA1 and HBA2 ... β-globin chains with different variants may interact to alleviate or exacerbate the effects of the individual variants. * ...
Timeline for Protein Hemoglobin, alpha-chain from a.1.1.2: Globins: *Protein Hemoglobin, alpha-chain from a.1.1.2: Globins ... Protein Hemoglobin, alpha-chain from a.1.1.2: Globins appears in SCOP 1.75. *Protein Hemoglobin, alpha-chain from a.1.1.2: ... Globins appears in SCOPe 2.02. *Protein Hemoglobin, alpha-chain from a.1.1.2: Globins appears in the current release, SCOPe ... Class a: All alpha proteins [46456] (284 folds). *. Fold a.1: Globin-like [46457] (2 superfamilies). core: 6 helices; folded ...
These data are compared with the near complete 3 noncoding region sequence of human alpha-globin mRNA obtained in these and ... and one third of the coding region of rabbit alpha-globin mRNA have thus been sequenced. ... A very similar insert in sequence has been described in human beta-globin mRNA (Proudfoot, 1977). ... dGdCdC hybridized to globin mRNA with reverse transcriptase, and sequenced using the plus and minus gel sequencing procedure ( ...
The alpha-globin pseudogene (psi alpha 1) is highly homologous to the alpha 2 and alpha 1 genes, but it lacks an HTF island. ... Clusters of CpG at the alpha 1 and alpha 2 genes resemble the HpaII tiny fragment (HTF) islands that are characteristic of ... CpG clusters are approximately 1.5 kb long and extend both upstream and downstream of the alpha-globin transcription start site ... Sequence comparison shows that a high proportion of CpGs in the alpha 2 gene are substituted by TpG or CpA in the pseudogene. ...
Alpha thalassemia is a blood disorder that reduces the production of hemoglobin . Explore symptoms, inheritance, genetics of ... A loss of two of the four alpha-globin alleles results in alpha thalassemia trait. People with alpha thalassemia trait may have ... Each person inherits two alpha-globin alleles from each parent. If both parents are missing at least one alpha-globin allele, ... As a result, there are four alleles that produce alpha-globin. The different types of alpha thalassemia result from the loss or ...
... thalassemia syndromes are a group of hereditary disorders characterized by a genetic deficiency in the synthesis of beta-globin ... 2] (Alpha thalassemia affects the alpha-globin gene[s].) These mutations, by causing impaired synthesis of the beta-globin ... The excess unpaired alpha-globin chains aggregate to form precipitates that damage red cell membranes, resulting in ... Beta-globin gene mutations. Mutations in globin genes cause thalassemias. Beta thalassemia affects one or both of the beta- ...
Proteintech Anti-Hemoglobin alpha Polyclonal, Catalog # 14537-1-AP. Tested in Western Blot (WB) and Immunoprecipitation (IP) ... alpha 1 globin; alpha globin 1; alpha one globin; Alpha-1/2-globin; alpha-2 globin chain; Alpha-globin; delta globin; globin, ... alpha; haemaglobin alpha 1; hemoglobin alpha 1 chain; hemoglobin alpha 1 globin chain; Hemoglobin alpha chain; hemoglobin alpha ... alpha-2 - alpha-1 - theta - 3. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ ...
Alpha globin gene duplications in beta thalassemia patients with intact beta globin gene. Faà V, Masala M, Cao A, Rosatelli MC. ... Thalassaemia-like carriers not linked to the beta-globin gene cluster. Faà V, Meloni A, Moi L, Ibba G, Travi M, Vitucci A, Cao ...
skin (jaundice).In Hb Bart syndrome and HbH disease, a shortage of alpha-globin ... carry oxygen to the bodys tissues. The ... Alpha thalassemia ... 2; HBA2 ALPHA-THALASSEMIA PubMed ... available. Citation on PubMed Chui DH. Alpha-thalassemia: Hb H ... form is caused by a particular variant in the HBB gene that results in the production of an abnormal version of beta-globin ...
Atrx (alpha thalassemia - short description of effect on globin genes) or ATRX by K. McDowell Arx Aristaless-like homeobox ( ... RAR-alpha Retinoic Acid Receptor (mouse) by D. Bravo de Laguna RAR-beta (Rat) by A. Firby RAR-beta (mouse) by S. McBean RAR- ... RXR-alpha(Mouse) by W. Assaily Ryk, Wnt3, Ephrins, and neural patterning (Chick) by N. Samaan Sevenless (sev - Drosophila) by A ...
Alpha-thalassemias are caused by deletion of a gene or genes from the globin chain. ... globin proteins instead of the two P-globin proteins. At some point during fetal development, a globin fetal switch occurs at ... Hemoglobin Isoforms [00118] Normal adult hemoglobin comprises four globin proteins, two of which are alpha (a) proteins and two ... 11C) Percentages y-globin mRNA expression of erythroid cells in BM determined by RT-qPCR. (FIG. 11D) Correlation of y-globin ...
... alpha2beta2). The clinical severity of beta-thalassemia is related to the imbalance between the alpha globin and non-alpha ... which is made up of two alpha globin and two beta globin chains ( ... Beta-thalassemia is caused by the reduced or absent beta globin ... globin chains [2,3,4].. Individuals with Beta-thalassemia major usually present with failure to thrive and progressive pallor ...
Reversing Zeta-Globin Transcriptional Silencing: Towards Embryonic Globin Induction in Patients With Severe Alpha-Thalassemia £ ...
Thalassemias are a group of disorders characterized by a decrease in either the alpha (ɑ) or beta (β) globin chain production ... individuals with both a hemoglobin E mutation on one of the beta-globin genes and a beta-globin gene deletion may have moderate ... Four conditions make up the α-thalassemias; each is defined by the number of inherited deletions of the four α-globin genes ... By comparison, in the same cohort, only 2% were carriers for alpha-thalassemia, 5% had beta-thalassemia, ,1% had sickle cell ...
... child inherits a copy of the mutated alpha and beta globin-producing genes from both of their parents  Decreased synthesis of ... Results in a decrease synthesis of the beta and alpha chains of hemoglobin  Condition is inherited from one of the parents ... alpha and beta chains of haemoglobin  Red blood cells cannot transport oxygen effectively around the body ...
Alpha-globin chains are transcribed on chromosome 16 (Fig. 1) and non-α-globin chains are transcribed on chromosome 11 (Fig. ... Alpha-thalassaemia. The clinical presentation is variable and depends on the number of α-globin genes that are deleted or ... The β-globin cluster is situated on the short arm of chromosome 11 (1 lpl5.5). On each chromosome, £-, δ- and β-globin chains ... Deficiency or absence of ß-globin chains results in a relative excess of α-globin chains which, unlike β- and Y-chains, cannot ...
The study showed that the reactivity of glycidamide with albumin, alpha-globin and beta-globin was much more than measured ... After 12 hours the glycidamideadduct levels for albumin < alpha-globin < beta-globin, but detectable adduct formation for ... In the current study the reaction products of acrylamide and glycidamide with human alpha- and beta-globins or albumin, ...
Alpha-thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes., Blood , ... Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemia., Ann. Hematol. , 96(11), 1921-1929, ...
UTR derived from mouse alpha-globin. Their key differences lie in the type of CleanCap® analog used and the sequence ...
The heme groups are shown as licorice, and the globin alpha-helices are drawn as black lines. ... Fig 4. (a) The alignment of the structures of twelve monomeric globins shows that the globin fold is well conserved. Despite ... the globin family exhibited no conservancy of the pathways at all between different globins, despite the fact that every globin ... An alignment of the different globin structures highlighting the conserved globin fold, along with the computed oxygen pathway ...
Now hemoglobin is made up of hemes and globins. There are 4 globin subunits, typically two alpha and two beta, and each one has ...
Avramova Z, Paneva E: Matrix attachment sites in the murine alpha-globin gene. Biochem Biophys Res Commun 1992, 182: 78-85. ... Jarman AP, Higgs DR: Nuclear scaffold attachment sites in the human globin gene complexes. EMBO J 1988, 7: 3337-3344. ... to the gammaA-globin gene binds to the nuclear matrix and interacts with special A-T-rich binding protein (SATB1), an SAR/MAR- ... globin locus utilizing a novel approach to quantitative real-time PCR. Nucleic Acids Res 2003, 31: 3257-3266. 10.1093/nar/ ...
Deletional Alpha Thalassemias (-3.7, SEA or MED). *Beta Globin Haplotyping. *Quantitative Hemoglobin Testing (HPLC and rp-HPLC) ...
... an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I\; two epsilon chains together with two alpha chains form ... The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains ... The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5-epsilon - G-gamma ...
... all targeted against the same region of rabbit alpha-globin leader sequence, were assessed in a cell-free translation system ... In vitro efficacy of Morpholino-modified antisense oligomers directed against tumor necrosis factor-alpha mRNA. J. Biol. Chem. ...
The 3 terminal sequences of human alpha and beta globin messenger RNAs: comparison with rabbit globin messenger RNA. ... The nucleotide sequences of the untranslated 5 regions of human alpha- and beta-globin mRNAs ... Sequence of the 3-noncoding and adjacent coding regions of human gamma-globin mRNA. scientific article published on December 1 ... Human beta-globin messenger RNA. III. Nucleotide sequences derived from complementary DNA ...
... a modified beta-globin protein) that combines with alpha globin to produce functional hemoglobin containing beta A-T87Q-globin ... Gene therapy that adds functional copies of a modified beta-globin gene into the patients hematopoietic stem cells (HSCs) ... CD34+ HSCs engraft in bone marrow and differentiate to produce RBCs containing biologically active beta A-T87Q-globin ( ...
  • Alpha thalassemia is a blood disorder that reduces the production of hemoglobin . (medlineplus.gov)
  • In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. (medlineplus.gov)
  • The more severe type is known as hemoglobin Bart hydrops fetalis syndrome, which is also called Hb Bart syndrome or alpha thalassemia major. (medlineplus.gov)
  • Both the HBA1 and HBA2 genes provide instructions for making a protein called alpha-globin, which is a component (subunit) of hemoglobin . (medlineplus.gov)
  • With a shortage of alpha-globin, cells make little or no normal hemoglobin. (medlineplus.gov)
  • The following product was used in this experiment: Hemoglobin alpha Polyclonal Antibody from Thermo Fisher Scientific, catalog # 14537-1-AP. (thermofisher.com)
  • alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. (thermofisher.com)
  • Alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia. (aafp.org)
  • Alpha thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis. (aafp.org)
  • Persons with thalassemia should be referred for preconception genetic counseling, and persons with alpha thalassemia trait should consider chorionic villus sampling to diagnose infants with hemoglobin Bart's, which increases the risk of toxemia and postpartum bleeding. (aafp.org)
  • Hemoglobin consists of an iron-containing heme ring and four globin chains: two alpha and two nonalpha. (aafp.org)
  • The composition of the four globin chains determines the hemoglobin type. (aafp.org)
  • Fetal hemoglobin (HbF) has two alpha and two gamma chains (alpha 2 gamma 2 ). (aafp.org)
  • Adult hemoglobin A (HbA) has two alpha and two beta chains (alpha 2 beta 2 ), whereas hemoglobin A2 (HbA2) has two alpha and two delta chains (alpha 2 delta 2 ). (aafp.org)
  • Beta-thalassemia is caused by the reduced or absent beta globin chain synthesis of hemoglobin (Hb) tetramer, which is made up of two alpha globin and two beta globin chains (alpha 2 beta 2 ). (springer.com)
  • Hemoglobin Subunit Zeta (Hbz) or Hba-x is a alpha-like hemoglobin and part of the globin family. (prospecbio.com)
  • Hemoglobin is made up of two pairs of globin chains. (msdmanuals.com)
  • Hemoglobin is made from two similar proteins, one called alpha-globin and one called beta-globin, that "stick together. (cdc.gov)
  • Initiation codon mutation of α2-globin Gene (HBA2:c.1delA), donor splice site mutation of α1-globin gene (IVSI-1, HBA1:c.95 + 1G>A), hemoglobin Queens Park/Chao Pra Ya (HBA1:c.98T>A) and hemoglobin Westmead (HBA2:c.369C>G). (bvsalud.org)
  • a novel frameshift beta globin gene mutation, resulting in Hemoglobin E/ß 0 thalassemia. (bvsalud.org)
  • Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes. (medlineplus.gov)
  • Deletions and nondeletion variants in one or more alleles reduce the amount of alpha-globin cells produce. (medlineplus.gov)
  • Nondeletion variants tend to reduce alpha-globin more than deletions. (medlineplus.gov)
  • Because nondeletion variants are usually more severe than deletions, nondeletion variants in two of the four alpha-globin alleles can result in HbH disease. (medlineplus.gov)
  • Peripheral smear in beta-zero thalassemia minor showing microcytes (M), target cells (T), and poikilocytes.The genetic defect usually is a missense or nonsense mutation in the beta-globin gene, although occasional defects due to gene deletions of the beta-globin gene and surrounding regions also have been reported. (medscape.com)
  • As genetic defects or deletions may affect one or more globin genes, a variety of clinical phenotypes may be encountered. (scielo.org.za)
  • Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. (medscape.com)
  • The thalassemias (named from the Greek word for sea, thalassa 1 ) are a group of inherited autosomal recessive hematologic disorders 2 that cause hemolytic anemia because of the decreased or absent synthesis of a globin chain. (aafp.org)
  • The thalassaemias are a group of inherited blood disorders characterised by decreased or absent globin chain synthesis. (scielo.org.za)
  • Major adult Hb (HbA) is composed of two β-globin chains and two alpha (α)-globin chains. (arupconsult.com)
  • β-globin chains with different variants may interact to alleviate or exacerbate the effects of the individual variants. (arupconsult.com)
  • Beta thalassemia syndromes are a group of hereditary disorders characterized by a genetic deficiency in the synthesis of beta-globin chains. (medscape.com)
  • In beta thalassemia major (ie, homozygous beta thalassemia), the production of the beta-globin chains is severely impaired because both beta-globin genes are mutated. (medscape.com)
  • The excess unpaired alpha-globin chains aggregate to form precipitates that damage red cell membranes, resulting in intravascular hemolysis. (medscape.com)
  • Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains. (aafp.org)
  • Imbalances of globin chains cause hemolysis and impair erythropoiesis. (aafp.org)
  • Alpha thalassemia is the result of deficient or absent synthesis of alpha globin chains, leading to excess beta globin chains. (aafp.org)
  • Alpha-globin chains are transcribed on chromosome 16 ( Fig. 1 ) and non- α -globin ' chains are transcribed on chromosome 11 ( Fig. 2 ) (discussed below). (scielo.org.za)
  • This questionnaire more globin polypeptide chains. (who.int)
  • Normally, adults have one pair of alpha chains and one pair of beta chains. (msdmanuals.com)
  • Typically, adults have two functional β-globin genes ( HBB ) and four functional α-globin genes (two copies each of HBA1 and HBA2 ). (arupconsult.com)
  • The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. (thermofisher.com)
  • Firstly, to confirm and, if possible, to narrow the regional localization of the human alpha-globin gene cluster on the short arm of chromosome 16. (gla.ac.uk)
  • The DNAs from the hybrid clones, as well as those from both parental origins, were screened for the presence of the human alpha-globin gene cluster. (gla.ac.uk)
  • A positive association (at a level of significance of 5%) between the presence/absence of the short arm of HC 16 and the presence/absence of the human alpha-globin gene cluster was found. (gla.ac.uk)
  • The value of different methods such as molecular hybridization in solution, in situ molecular hybridization and trisomy mapping, in assigning single copy genes to chromosome regions is discussed taking the human alpha-globin gene cluster as the model system. (gla.ac.uk)
  • β thalassemia and certain hemoglobinopathies are caused by pathogenic germline variants within the HBB gene or variants involving the beta globin gene cluster and its regulatory elements. (arupconsult.com)
  • Association of two DNA polymorphisms in the alpha-globin gene cluster: implications for genetic analysis. (ox.ac.uk)
  • These mutations, by causing impaired synthesis of the beta-globin protein component of Hb, result in anemia. (medscape.com)
  • The defect can be a complete absence of the beta-globin protein (ie, beta-zero thalassemia) or a severely reduced synthesis of the beta-globin protein (ie, beta-plus thalassemia). (medscape.com)
  • In beta thalassemia minor (ie, beta thalassemia trait or heterozygous carrier-type), one of the beta-globin genes is defective, resulting in an approximately 50% decrease in the synthesis of the beta-globin protein. (medscape.com)
  • 3 The transition from gamma globin synthesis (HbF) to beta globin synthesis (HbA) begins before birth. (aafp.org)
  • The thalassaemias are a group of inherited disorders that result in a reduction or absence of globin chain synthesis. (scielo.org.za)
  • The alpha-thalassemia-2 (alpha-thal-2) genotype or mild alpha-thalassemia gene consists of a single structural alpha-globin gene on the chromosome that normally bears two alpha-globin genes. (scienceopen.com)
  • The human β-globin locus is composed of five genes located on a short region of chromosome 11, responsible for the creation of the beta parts (roughly half) of the oxygen transport protein Haemoglobin. (wikipedia.org)
  • Alpha globin chain production is controlled by two genes on each chromosome 16 ( Table 1 4 , 5 ). (aafp.org)
  • Many CRMs have been mapped within the cluster of genes encoding β-like globins expressed in embryonic (HBE1), fetal (HBG1 and HBG2), and adult (HBB and HBD) erythroid cells. (wikipedia.org)
  • This locus contains not only the beta globin gene but also delta, gamma-A, gamma-G, and epsilon globin. (wikipedia.org)
  • Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. (ox.ac.uk)
  • We have analysed CpG frequency and CpG methylation across part of the human alpha-globin locus. (ox.ac.uk)
  • These features are not found at genes of the beta-globin locus. (ox.ac.uk)
  • Variants in the beta (β)-globin gene ( HBB ) can result in anemia, β thalassemia, or sickling disorders of varying severity. (arupconsult.com)
  • Clinical presentation and molecular identification of four uncommon alpha globin variants in Thailand. (bvsalud.org)
  • Classification of thalassaemia is based on the type of globin chain that is deficient. (scielo.org.za)
  • Similarly, with HbF being the major subfraction in the fetus, γ -thalassaemia is likely to cause varying degrees of anaemia in the fetus, depending on the number of γ -globin genes inactivated or deleted. (scielo.org.za)
  • Alpha-globin gene triplications are not associated with abnormal haematological parameters but may aggravate the phenotype of patients with beta-thalassaemia. (ithanet.eu)
  • Alpha thalassaemia in tribal communities of coastal Maharashtra, India. (medscape.com)
  • Alpha(+)-thalassaemia and malarial anaemia. (medscape.com)
  • A reverse dot-blot method for rapid detection of non-deletion alpha thalassaemia. (medscape.com)
  • Haas PS, Roy NB, Gibbons RJ, Deville MA, Fisher C, Schwabe M. The role of X-inactivation in the gender bias of patients with acquired alpha-thalassaemia and myelodysplastic syndrome (ATMDS). (medscape.com)
  • Less commonly, changes to the DNA sequence in or near these genes cause alpha thalassemia. (medlineplus.gov)
  • Mutations in globin genes cause thalassemias . (medscape.com)
  • Therefore, a child can only have SCD having SCT is that when both of his/her parents have at least one abnormal you could have a beta-globin gene. (cdc.gov)
  • Genes are the instructions that control how red blood cells make alpha- and beta-globin proteins. (cdc.gov)
  • A loss of one alpha-globin allele is found in alpha thalassemia silent carriers. (medlineplus.gov)
  • A single gene deletion results in alpha thalassemia silent carrier status, which is asymptomatic with normal hematologic findings. (aafp.org)
  • Alpha thalassemia also occurs frequently in people from Mediterranean countries, Africa, the Middle East, India, and Central Asia. (medlineplus.gov)
  • Nucleotide sequence of the 3' terminal third of rabbit alpha-globin messenger RNA: comparison with human alpha-globin messenger RNA. (ox.ac.uk)
  • The complete 3' noncoding region, 89 nucleotides in length, and one third of the coding region of rabbit alpha-globin mRNA have thus been sequenced. (ox.ac.uk)
  • The leftward deletion was found in four and the nondeletion alpha-thalassemia lesion was found in five of the nine remaining Chinese subjects. (scienceopen.com)
  • Incidence of alpha-globin gene defect in the Lebanese population: a pilot study. (cdc.gov)
  • There are four globin chain subtypes, viz. (scielo.org.za)
  • If a strong suspicion exists and if a definitive answer is required, polymerase chain reaction (PCR) evaluation should be performed for globin-chain analysis. (medscape.com)
  • Approximately 5 percent of the world's population has a globin variant, but only 1.7 percent has alpha or beta thalassemia trait. (aafp.org)
  • A): a new silent ß-globin gene variant found in coexistence with a-thalassemia in a family of African origin. (medscape.com)
  • People with alpha thalassemia trait may have unusually small, pale red blood cells and mild anemia. (medlineplus.gov)
  • The two-gene deletion causes alpha thalassemia trait (minor) with microcytosis and usually no anemia. (aafp.org)
  • In alpha-thalassemia minor and beta-thalassemia minor, people have mild anemia with no symptoms. (msdmanuals.com)
  • Hb Bart syndrome, the most severe form of alpha thalassemia, results from the loss or alteration of all four alpha-globin alleles. (medlineplus.gov)
  • These data are compared with the near complete 3' noncoding region sequence of human alpha-globin mRNA obtained in these and previous studies. (ox.ac.uk)
  • A very similar insert in sequence has been described in human beta-globin mRNA (Proudfoot, 1977). (ox.ac.uk)
  • In the current study the reaction products of acrylamide and glycidamide with human alpha- and beta-globins or albumin, obtained through in vitro incubation, were studied using Surface Enhanced Laser Desorption Ionization (SELD) with Time of Flight mass spectrometry. (cdc.gov)
  • Beta thalassemia affects one or both of the beta-globin genes. (medscape.com)
  • [ 2 ] ( Alpha thalassemia affects the alpha-globin gene[s]. (medscape.com)
  • Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype. (scienceopen.com)
  • Embury SH, Miller JA, Dozy AM, Kan YW, Chan V, Todd D, Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype. (ithanet.eu)
  • Prevalence study and molecular characterization of alpha-thalassemia in Filipinos. (medscape.com)
  • Two different patterns of gene organization responsible for the alpha-thal-2 genotype were found: the first was the result of a 4.2-kilobase pair deletion involving the normal 5' alpha-globin gene (leftward deletion alpha-thal-2 genotype), and the second probably the result of a crossover deletion of a DNA fragment bridging the two normal alpha-globin genes (rightward deletion alpha-thal-2- genotype). (scienceopen.com)
  • A new polymorphic BgI II restriction endonuclease site in the alpha-globin gene complex has been found in Cypriot, Sardinian, and Greek populations. (ox.ac.uk)
  • Such changes prevent the production of any normal alpha-globin. (medlineplus.gov)
  • HbH disease is usually caused by loss or alteration of three of the four alpha-globin alleles, which sharply reduces the amount of normal alpha-globin produced. (medlineplus.gov)
  • SCT occurs when a person inherits a gene for sickle beta- globin from one parent and a gene for normal beta-globin from the other parent. (cdc.gov)
  • As a result, there are four alleles that produce alpha-globin. (medlineplus.gov)
  • The different types of alpha thalassemia result from the loss or alteration of some or all of these alleles. (medlineplus.gov)
  • A loss of two of the four alpha-globin alleles results in alpha thalassemia trait. (medlineplus.gov)
  • Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymptomatic and require no treatment. (aafp.org)
  • Alpha thalassemia occurs most often in persons of African and Southeast Asian descent, and beta thalassemia is most common in persons of Mediterranean, African, and Southeast Asian descent. (aafp.org)
  • CpG clusters are approximately 1.5 kb long and extend both upstream and downstream of the alpha-globin transcription start site. (ox.ac.uk)
  • Alpha-thalassemia: Hb H disease and Hb Barts hydrops fetalis. (medscape.com)
  • Alpha-thalassemia is most common in people with African or Black American, Mediterranean, or Southeast Asian ancestry. (msdmanuals.com)
  • All people have two genes for making beta-globin. (cdc.gov)
  • Sequence comparison shows that a high proportion of CpGs in the alpha 2 gene are substituted by TpG or CpA in the pseudogene. (ox.ac.uk)
  • Alpha thalassemia is a fairly common blood disorder worldwide. (medlineplus.gov)
  • Most HPVs belong to genera alpha (e.g., genital and wart-associated types), beta, or gamma (cutaneous types) ( 1 ). (cdc.gov)