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20-September-2008 09:55:53 - Duffy antigen system Duffy antigen Identifiers Symbol DARC Entrez 2532 HUGO 4035 OMIM 110700 RefSeq NM_002036 UniProt Q16570 Other data Locus Chr. 1 q21-q22 The Duffy antigen system is a blood system in which a pair of proteins appears on the outside of red blood cells. It was named after the patient in which it was discovered.1 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 Caucasians are Duffy-positive, and a majority of those of African descent are Duffy-negative.2 Since most Duffy-negative people are of African origin, this is one reason why encouraging blood donations from people of African origins is critically important to the health of other people of the same race. In 1950 the Duffy antigen was discovered in a multiply transfused hemophiliac 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: Fya+b+, Fya+b-, and Fya-b+. Contents 1 Genetics and genomics 1.1 Relationship to HIV 2 Molecular biology 3 References 4 External links 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 - FYA and FYB - coding for the Fya and Fyb antigens respectively, FYX and FYFy, five phenotypes Fy-a, Fy-b, Fy-o, Fy-x and Fy-y and five antigens. 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 Fya-b- phenotype is a point mutation in the erythroid specific promoter. 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. 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 Fya-b-: 68% in African Americans and 88-100% in African blacks including more than 90% of West African blacks.3 This phenotype is exceedingly rare in whites. The silent allele has evolved at least twice in the black population of Africa and evidence for selection for this allele has been found.4 The selection pressure involved here appears to be more complex than many text books might suggest.5 An independent evolution of this phenotype occurred in Papua New Guinea has also been documented.6 While a possible role in the protection of humans from malaria had been previously suggested this was only confirmed clinically in 1976. 7 Since then many surveys have been done to elucidate the prevalence of these alleles in different populations. The mutation Ala100Thr G - A in the first codon position - base number 298 within the FYB allele was thought to be purely a Caucasian genotype, but has since been described in Brazilians.8 This antigen along with other blood group antigens was used to identify the Basque people as a genetically separate group.9 Its use in forensic science is under consideration.10 The Andaman and Nicobar Islands, now part of India, were originally inhabited by 14 aboriginal tribes. Several of these have gone extinct. One surviving tribe - the Jarawas - live in three jungle areas of South Andaman and one jungle area in Middle Andaman. The area is endemic for malaria. The causative species is Plasmodium falciparum: there is no evidence for the presence of Plasmodium vivax. Blood grouping revealed an absence of both Fya and Fyb antigens in two areas and a low prevalence in two others.11 In the Yemenite Jews the frequency of the Fy allele is 0.5879.12 The frequency of this allelle varies from 0.1083 to 0.2191 among Jews from the Middle East, North Africa and Southern Europe. In the Chinese ethnic populations - the Han and the She people - the frequencies of Fya and Fyb alleles were 0.94 and 0.06 and 0.98 and 0.02 respectively.13 In Grande Comore also known as Ngazidja the frequency of the Fya- b- phenotype is 0.86.14 In a survey of 115 unrelated Tunisians using both serological and DNA based methods gave the following results: FYX frequency 0.0174; FY1 = 0.291 expressed 0.260, silent 0.031; FY2 = 0.709 expressed 0.427; silent 0.282. FY2 silent is the most common allele in West African blacks and the high prevalence in this sample was interpreted as historical admixture. 15 Relationship to HIV A connection has been found between HIV susceptibility and the Duffy antigen expression. The presence of the DARC receptor appears to increase the susceptibility to infection by HIV. However once established, the DARC receptor then slows down the progression of the disease16. 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: melanoma growth stimulatory activity MGSA,17 regulated upon activation normal T expressed and secreted RANTES; CCL518 monocyte chemotatic protein-1 MCP-1; CCL219 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 Chemokines. The binding site appears to be localised to the amino terminus.20 While Duffy is expressed on erythrocytes the Duffy antigen is found on some epithelial cells, Purkinje cells of the cerebellum,21 endothelial cells of thyroid capillaries, the post-capillary venules of some organs22 and the large pulmonary venules. 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. 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 believed to be resistant to merozoite invasion,23 although the American journal of tropical medicine and hygiene has reported P. vivax infection in Duffy negative children in Kenya, suggesting a role in resistance to disease, not infection.24 This antigen may also play a role in erythrocyte invasion in the rodent malarial parasite Plasmodium yoelii. 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.25 This hypothesis has also been questioned after knock out mice were created. These animals appeared healthy and had normal responses to infection. While the function of the Duffy antigen remains presently 2006 unknown, evidence is accumulating that suggests a role in neutrophil migration from the blood into the tissues26 and in modulating the inflammatory response.27282930313233343536 It may also play a role in the control of cancer.37 References ^ Cutbush, Marie; Mollison, PL; Parkin, Dorothy M 4 February 1950. A New Human Blood Group PDF. Nature 165 188 - 189: 188. doi:10.1038/165188b0. Retrieved on 2007-06-08. ^ Nickel RG, Willadsen SA, Freidhoff LR, et al 1999. Determination of Duffy genotypes in three populations of African descent using PCR and sequence-specific oligonucleotides. Hum. Immunol. 60 8: 738-42. doi:10.1016/S0198-88599900039-7. PMID 10439320. ^ Levinson, Warren E. 2004-06-24. Medical Microbiology Immunology, 8, McGraw-Hill/Appleton Lange, 644. ISBN 0071431993. ^ Hamblin M.T., Di Rienzo A. 2000 Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. Am. J. Hum. Genet. 665:1669-1679. ^ Hamblin M.T., Thompson E.E., Di Rienzo A. 2002 Complex signatures of natural selection at the Duffy blood group locus. Am. J. Hum. Genet. 702:369-383. ^ Zimmerman, P A; I Woolley, G L Masinde, S M Miller, D T McNamara, F Hazlett, C S Mgone, M P Alpers, B Genton, B A Boatin, J W Kazura 1999-11-23. Emergence of FYAnull in a Plasmodium vivax-endemic region of Papua New Guinea. Proceedings of the National Academy of Sciences of the United States of America 96 24: 13973-7. doi:10570183 inactive 2008-08-08. ISSN 0027-8424. Retrieved on 2008-08-08. ^ Miller L.H., Mason S.J., Clyde D.F, McGinniss M.H. 1976 The resistance factor to Plasmodium vivax in blacks: the Duffy-blood-group genotype, FyFy. N. Engl. J. Med. 295:302-304 ^ Estalote AC, Proto-Siqueira R, Silva WA, Zago MA, Palatnik M 2005. The mutation G298A--Ala100Thr on the coding sequence of the Duffy antigen/chemokine receptor gene in non-caucasian Brazilians. Genet. Mol. Res. 4 2: 166-73. PMID 16110438. ^ Bauduer F, Feingold J, Lacombe D 2005. The Basques: review of population genetics and Mendelian disorders. Hum. Biol. 77 5: 619-37. doi:10.1353/hub.2006.0001. PMID 16596943. ^ Ferri G, Bini C, Ceccardi S, Ingravallo F, Lugaresi F, Pelotti S 2006. Minisequencing-based genotyping of Duffy and ABO blood groups for forensic purposes. J. Forensic Sci. 51 2: 357-60. doi:10.1111/j.1556-4029.2006.00058.x. PMID 16566771. ^ Das MK, Singh SS, Adak T, Vasantha K, Mohanty D 2005. The Duffy blood groups of Jarawas - the primitive and vanishing tribe of Andaman and Nicobar Islands of India. Transfusion medicine Oxford, England 15 3: 237-40. doi:10.1111/j.1365-3148.2005.00583.x inactive 2008-06-22. PMID 15943709. ^ Kobyliansky E, Micle S, Goldschmidt-Nathan M, Arensburg B, Nathan H 1980. Duffy, Kell and P blood group systems in some Jewish populations of Israel. Acta anthropogenetica 4 3-4: 173-9. PMID 7346047. ^ Yan L, Zhu F, Fu Q, He J 2005. ABO, Rh, MNS, Duffy, Kidd,Yt, Scianna, and Colton blood group systems in indigenous Chinese. Immunohematology / American Red Cross 21 1: 10-4. PMID 15783300. ^ Chiaroni J, Touinssi M, Frassati C, et al 2004. Genetic characterization of the population of Grande Comore Island Njazidja according to major blood groups. Hum. Biol. 76 4: 527-41. doi:10.1353/hub.2004.0053. PMID 15754970. ^ Sellami, M H; H Kaabi, B Midouni, A Dridi, N Mojaat, M K Boukef, S Hmida. Duffy blood group system genotyping in an urban Tunisian population. Annals of Human Biology 35 4: 406-15. doi:793242171 inactive 2008-08-08. ISSN 1464-5033. Retrieved on 2008-08-08. ^ He, Weijing; Stuart Neil, Hemant Kulkarni, Edward Wright, Brian K Agan, Vincent C Marconi, Matthew J Dolan, Robin A Weiss, Sunil K Ahuja 2008-07-17. Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe 4 1: 52-62. doi:S1931-31280800190-X inactive 2008-08-08. ISSN 1934-6069. Retrieved on 2008-08-08. ^ Horuk R, Chitnis CE, Darbonne WC, et al 1993. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 261 5125: 1182-4. doi:10.1126/science.7689250. PMID 7689250. ^ Horuk R, Wang ZX, Peiper SC, Hesselgesser J 1994. Identification and characterization of a promiscuous chemokine-binding protein in a human erythroleukemic cell line. J. Biol. Chem. 269 26: 17730-3. PMID 7517400. ^ Chaudhuri A, Zbrzezna V, Polyakova J, Pogo AO, Hesselgesser J, Horuk R 1994. Expression of the Duffy antigen in K562 cells. Evidence that it is the human erythrocyte chemokine receptor. J. Biol. Chem. 269 11: 7835-8. PMID 8132497. ^ Lu ZH, Wang ZX, Horuk R, et al 1995. The promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines is primarily localized to sequences in the amino-terminal domain. J. Biol. Chem. 270 44: 26239-45. PMID 7592830. ^ Horuk R, Martin AW, Wang Z, et al 1997. Expression of chemokine receptors by subsets of neurons in the central nervous system. J. Immunol. 158 6: 2882-90. PMID 9058825. ^ Hadley TJ, Lu ZH, Wasniowska K, et al 1994. Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen. J. Clin. Invest. 94 3: 985-91. doi:10.1172/JCI117465. PMID 8083383. ^ Miller LH, Mason SJ, Clyde DF, McGinniss MH 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N. Engl. J. Med. 295 6: 302-4. PMID 778616. ^ Ryan JR, Stoute JA, Amon J, et al 2006. Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in Western Kenya. Am. J. Trop. Med. Hyg. 75 4: 575-81. PMID 17038676. ^ Fukuma N, Akimitsu N, Hamamoto H, Kusuhara H, Sugiyama Y, Sekimizu K 2003. A role of the Duffy antigen for the maintenance of plasma chemokine concentrations. Biochem. Biophys. Res. Commun. 303 1: 137-9. doi:10.1016/S0006-291X0300293-6. PMID 12646177. ^ Lee JS, Frevert CW, Wurfel MM, et al 2003. Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J. Immunol. 170 10: 5244-51. PMID 12734373. ^ Dawson TC, Lentsch AB, Wang Z, et al 2000. Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines DARC. Blood 96 5: 1681-4. PMID 10961863. ^ Patterson AM, Siddall H, Chamberlain G, Gardner L, Middleton J 2002. Expression of the duffy antigen/receptor for chemokines DARC by the inflamed synovial endothelium. J. Pathol. 197 1: 108-16. doi:10.1002/path.1100. PMID 12081195. ^ Liu XH, Hadley TJ, Xu L, Peiper SC, Ray PE 1999. Up-regulation of Duffy antigen receptor expression in children with renal disease. Kidney Int. 55 4: 1491-500. doi:10.1046/j.1523-1755.1999.00385.x. PMID 10201015. ^ Rot A 2005. Contribution of Duffy antigen to chemokine function. Cytokine Growth Factor Rev. 16 6: 687-94. doi:10.1016/j.cytogfr.2005.05.011. PMID 16054417. ^ Segerer S, Regele H, MacK M, et al 2000. The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Kidney Int. 58 4: 1546-56. doi:10.1046/j.1523-1755.2000.00316.x. PMID 11012889. ^ Segerer S, Cui Y, Eitner F, et al 2001. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am. J. Kidney Dis. 37 3: 518-31. PMID 11228176. ^ Brühl H, Vielhauer V, Weiss M, Mack M, Schlöndorff D, Segerer S 2005. Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology Oxford, England 44 3: 309-13. doi:10.1093/rheumatology/keh485. PMID 15572394. ^ Middleton J, Americh L, Gayon R, et al 2005. A comparative study of endothelial cell markers expressed in chronically inflamed human tissues: MECA-79, Duffy antigen receptor for chemokines, von Willebrand factor, CD31, CD34, CD105 and CD146. J. Pathol. 206 3: 260-8. doi:10.1002/path.1788. PMID 15887283. ^ Segerer S, Böhmig GA, Exner M, et al 2003. When renal allografts turn DARC. Transplantation 75 7: 1030-4. doi:10.1097/01.TP.0000054679.91112.6F. PMID 12698093. ^ Pruenster M, Rot A 2006. Throwing light on DARC. Biochem. Soc. Trans. 34 Pt 6: 1005-8. doi:10.1042/BST0341005. PMID 17073738. ^ Zijlstra A, Quigley JP 2006. The DARC side of metastasis: shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Cancer Cell 10 3: 177-8. doi:10.1016/j.ccr.2006.08.012. PMID 16959609. External links Duffy at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH Duffy gene Population data v d e Transfusion medicine General concepts Apheresis Plasmapheresis, Plateletpheresis, Leukapheresis - Blood transfusion - Coombs test - Cross-matching - Exchange transfusion - International Society of Blood Transfusion - Intraoperative blood salvage - ISBT 128 - Transfusion reactions Human blood group systems - Blood type ABO - Chido-Rodgers - Colton - Cromer - Diego - Dombrock - Duffy - Gerbich - GIL - Hh - Ii - Indian - JMH - Kell Xk - Kidd - Knops - LW - Lewis - Lutheran - MNS - OK - P - Raph - Rh - Scianna - T-Tn - Xg - Yt - Other Blood products Blood donation - Blood substitutes - Cryoprecipitate - Platelets - Plasma - Red blood cells - Whole blood Retrieved from http://en..org/wiki/Duffy_antigen_system Categories: Genes on chromosome 1 | Immune system | Transfusion medicine | Blood antigen systemsHidden categories: Pages with DOIs broken since 2008 | Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 8 August 2008, at 09:16
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