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Encyclopedia > Duffy antigen system
[[Image:|250px|Duffy antigen chemical structure]]
Duffy antigen
Identifiers
Symbol(s) DARC
Entrez 2532
OMIM 110700
RefSeq NM_002036
UniProt Q16570
PDB [1]
Other data
EC number [2]
Locus Chr. 1 q21-q22

The Duffy antigen is a pair of proteins which appears on the outside of red blood cells. A person who has "Duffy negative" blood (no Duffy antigen naturally present) may be allergic, perhaps seriously allergic, to a blood transfusion which is "Duffy positive" (has this pair of proteins). Nearly all white people are Duffy-positive; nearly all black African people are Duffy-negative. Since most Duffy-negative people are of African origin, this is one reason why encouraging blood donations from people of African origins are critically important to the health of other people of the same race. Hugo is a masculine name. ... The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... In biology and evolutionary computation, a locus is the position of a gene (or other significant sequence) on a chromosome. ... Chromosome 1 is, by convention, the designation for the largest human chromosome. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen from the lungs or gills to body tissues via the blood. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ...


In 1950 the Duffy antigen was discovered in a multiply transfused hemophiliac in whose serum contained the first example of anti-Fya. In 1951 the antibody to a second antigen, Fyb, was discovered in the serum of a woman who had been pregnant three times. Using these antibodies three common phenotypes were defined: Fy(a+b+), Fy(a+b-), and Fy(a-b+). 1950 (MCML) was a common year starting on Sunday (link will take you to calendar). ... Haemophilia or hemophilia is the name of any of several hereditary genetic illnesses that impair the bodys ability to control bleeding. ... 1951 (MCMLI) was a common year starting on Monday; see its calendar. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Blood plasma is a component of blood. ... The phenotype of an individual organism is either its total physical appearance and constitution, or a specific manifestation of a trait, such as size or eye color, that varies between individuals. ...

Contents


Genetics and genomics

The Duffy antigen gene (gp-Fy; CD234) is located on the long arm of chromosome 1 (1.q22-1.q23) and was cloned in 1993. It is a single copy gene and encodes a 336 amino acid acidic glycoprotein. The gene carries the antigenic determinants of the Duffy blood group system consisting of four alleles (FY*A and FY*B - coding for the Fya and Fyb antigens, respectively - FY*X and FY*Fy), five phenotypes and five antigens (Fy-a, Fy-b, Fy-o). Fya and Fyb differ by in a single amino acid at position 43: aspartic acid in Fya and glycine in Fyb. The genetic basis for the Fy(a-b-) phenotype is a point mutation in the erythroid specific promoter. An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: Chromosome. ... 1993 (MCMXCIII) was a common year starting on Friday of the Gregorian calendar and marked the Beginning of the International Decade to Combat Racism and Racial Discrimination (1993-2003). ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... An allele is any one of a number of viable DNA codings of the same gene (sometimes the term refers to a non-gene sequence) occupying a given locus (position) on a chromosome. ... The phenotype of an individual organism is either its total physical appearance and constitution or a specific manifestation of a trait, such as size, eye color, or behavior that varies between individuals. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... An amino acid residue is what is left of an amino acid once a molecule of water has been lost (an H+ from the nitrogenous side and an OH- from the carboxylic side) in the formation of a peptide bond. ... Aspartic acid, also known as aspartate, the name of its anion, is one of the 20 natural proteinogenic amino acids which are the building blocks of proteins. ... Glycine (Gly, G) is a nonpolar amino acid. ... The phenotype of an individual organism is either its total physical appearance and constitution or a specific manifestation of a trait, such as size, eye color, or behavior that varies between individuals. ... A point mutation, or hellboy is such a cool kid i mean come on! ride that yomer crusin up the street yeeeha! substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ...


The Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon. Most Duffy negative blacks carry a silent Fy-b allele with a single T to C substitution at nucleotide -46, impairing the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. The gene is still transcribed in non erythroid cells in the presence of this mutation. Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Exons are the regions of DNA within a gene that are not spliced out from the transcribed RNA and are retained in the final messenger RNA (mRNA) molecule. ... An allele is any one of a number of viable DNA codings of the same gene (sometimes the term refers to a non-gene sequence) occupying a given locus (position) on a chromosome. ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... In genetics, a promoter is a DNA sequence that enables a gene to be transcribed. ... In molecular biology, a transcription factor is a protein that binds DNA at a specific promoter or enhancer region or site, where it regulates transcription. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... In biology, mutations are changes to the genetic material (usually DNA or RNA). ...


Differences in the racial distribution of the Duffy antigens were discovered in 1954 when it was found that the majority of blacks had the erythrocyte phenotype Fy(a-b-): 68% in African Americans and 88–100% in African blacks (including more than 90% of West African blacks).[1] This phenotype is exceedingly rare in whites. 1954 (MCMLIV) was a common year starting on Friday of the Gregorian calendar. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... The phenotype of an individual organism is either its total physical appearance and constitution or a specific manifestation of a trait, such as size, eye color, or behavior that varies between individuals. ... An African American (also Afro-American, Black American, or simply black), is a member of an ethnic group in the United States whose ancestors, usually in predominant part, were indigenous to Africa. ... Africa is the worlds second-largest and second-most populous continent, after Asia. ...  Western Africa (UN subregion)  Maghreb West Africa or Western Africa is the westernmost region of the African continent. ... The phenotype of an individual organism is either its total physical appearance and constitution or a specific manifestation of a trait, such as size, eye color, or behavior that varies between individuals. ...


Molecular biology

Duffy has been found to act as a multispecific receptor for chemokines of both the C-C and C-X-C families, including: MGSA, regulated upon activation normal T expressed and secreted (RANTES; CCL5), monocyte chemotatic protein-1 (MCP-1; CCL2) and the angiogenic CXC chemokines interleukin-8 (IL-8, CXCL8), growth related gene alpha (GRO-α, CXCL1), neutrophil activating peptide-2 (NAP-2, CXCL7) and ENA-78 (CXCL5). Consequently the Fy protein is also known as DARC (Duffy Antigen Receptor for Chenokines). Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ... Interleukin-8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells. ...


While Duffy is expressed on erythrocytes the Duffy antigen is found on some epithelial cells, Purkinje cells of the cerebellum, endothelial cells of thyroid capillaries, the post-capillary venules of some organs and the large pulmonary venules. Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Figure 1a: A human brain, with the cerebellum in purple. ... The word capillary is used to describe any very narrow tube or channel through which a fluid can pass. ... A venule is a small blood vessel that allows blood to return from the capillary beds to the larger blood vessels called veins. ...


The antigen is predicted to have 7 transmembrane domains, an exocellular N-terminal domain and an endocellular C-terminal domain. Alignment with other seven transmembrane G-protein-coupled receptors shows that DARC lacks the highly conserved DRY motif in the second intracellular loop of the protein that is known to be associated with G-protein signaling. Consistent with this finding ligand binding by DARC does not induce G-protein coupled signal transduction nor a Ca2+ flux unlike other chemokine receptors. Based on these alignments the Duffy antigen is considered to be most similar to the interleukin-8B receptors. The seven transmembrane α-helix structure of a G-protein-coupled receptor. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ...


On erythrocytes the Duffy antigen acts as a receptor for invasion by the human malarial parasites Plasmodium vivax and Plasmodium knowlesi; Duffy negative individuals whose erythrocytes do not express the receptor are resistant to infection. This antigen may also play a role in erythrocyte invasion in the rodent malarial parasite Plasmodium yoelii. Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Malaria (Medieval Italian: mala aria — bad air) and formerly called ague or marsh fever in English, is an infectious disease which causes about 350–500 million infections in humans and approximately 1. ... Binomial name Plasmodium vivax Grassi & Feletti 1890 The parasite Plasmodium vivax is the most frequent and widely distributed cause of benign, but recurring (tertian), malaria. ... Binomial name Plasmodium knowlesi Plasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ...


In DARC-transfected cells, DARC is internalized following ligand binding and this led to the hypothesis that expression of DARC on the surface of erythrocytes, endothelial, neuronal cells and epithelial cells may act as a sponge and provide a mechanism by which inflammatory chemokines may be removed from circulation as well as their concentration modified in the local environment. This hypothesis has also been questioned after knock out mice were created. These animals appeared healthy and had normal responses to infection. The function of the Duffy antigen remains presently (2004)unknown. Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... In zootomy, epithelium is a tissue composed of a layer of cells. ... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ... A gene knockout is a genetically engineered organism that carries one or more genes in its chromosomes that has been made inoperative. ... 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ...


References

  1. ^ Levinson, W. 2004. Medical Microbiology and Immunology. Lange Medical Books: New York. ISBN 0-07-143199-3

External links

  • Duffy gene
  • Population data
Transfusion medicine - edit
Blood transfusion | Cross-matching | Coombs test | Intraoperative blood salvage | Transfusion reactions | International Society of Blood Transfusion | ISBT 128 | Platelet transfusion |
Human blood group systems - Blood type
ABO | Rhesus | Duffy | Hh | Kell | Kidd | Kx | Colton | Yt
Blood products
Blood donation | Blood | Plasma | Platelets | Cryoprecipitate | Plasmapheresis | Red blood cells 

 
 

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