afro-brazilians tested) were also related to one another, as one was a mother and the other her daughter. this antigen along with other blood group antigens was used to identify the basque people as a genetically separate group. its use in forensic science is under consideration. the andaman and nicobar islands, 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 fy(a) and fy(b) antigens in two areas and a low prevalence in two others. in the yemenite jews the frequency of the fy allele is 0.5879 the frequency of this allele varies from 0.1083 to 0.2191 among jews from the middle east, north africa and southern europe. the incidence of fya among ashkenazi jews is 0.44 and among the non-ashkenazi jews it is 0.33. the incidence of fyb is higher in both groups with frequencies of 0.53 and 0.64 respectively. 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. the frequency of the fya allele in most asian populations is ~95%. in grande comore (also known as ngazidja) the frequency of the fy(a- b-) phenotype is 0.86. the incidence of fy(a+b-) in northern india among blood donors is 43.85%. in the maghreb, horn of africa and the nile valley, the afroasiatic (hamitic-semitic) speaking populations are largely duffy-positive. between 70%-98% of hamito-semitic groups in ethiopia were found to be duffy-positive. serological and dna based analysis of 115 unrelated tunisians also found an fy*x frequency of 0.0174; fy*1 = 0.291 (expressed 0.260, silent 0.031); fy*2 = 0.709 (expressed 0.427; silent 0.282). since the fy*2 silent is the most common allele in west africa, its minor occurrence in the sample probably represents recent diffusion from the latter region. in nouakchott, mauritania overall 27% of the population are duffy-positive. 54% of moors are duffy antigen positive, while only 2% of black ethnic groups (mainly poular, soninke and wolof) are duffy positive. a map of the duffy antigen distribution has been produced. the most prevalent allele globally is fy*a. across sub-saharan africa the predominant allele is the silent fy*bes variant. in iran the fy (a-b-) phenotype was found in 3.4%. there appears to have been a selective sweep in africa which reduced the incidence of this antigen there. this sweep appears to have occurred between 6,500 and 97,200 years ago (95% confidence interval) the distribution within india has been studied in some detail. clinical significance historically the role of this antigen other than its importance as a receptor for plasmodium protozoa has not been appreciated. recent work has identified a number of additional roles for this protein. malaria on erythrocytes, the duffy antigen acts as a receptor for invasion by the human malarial parasites p. vivax and p. knowlesi. this was first shown in 1980. duffy negative individuals whose erythrocytes do not express the receptor are believed to be resistant to merozoite invasion although p. vivax infection has been reported in duffy negative children in kenya, suggesting a role in resistance to disease, not infection. this antigen may also play a role in erythrocyte invasion in the rodent malarial parasite p. yoelii. the epitope fy6 is required for p. vivax invasion. the protection to p. vivax malaria conferred by the absence of the duffy antigen appears to be very limited at best in madagascar. although 72% of the population are duffy antigen negative, 8.8% of the duffy antigen negative individuals were asymptomatic carriers of p. vivax. malaria has also been found in angola and equatorial guinea in duffy negative individuals. p. vivax malaria in a duffy antigen negative individual in mauritania has also been reported. similar infections have been reported in brazil and kenya. additional cases of infection in duffy antigen negative individuals have been reported from the congo and uganda. a study in brazil of the protection against p. vivax offered by the lack of the duffy antigen found no differential resistance to malaria vivax between duffy antigen positive and negative individuals. nancy ma's night monkey (a. nancymaae) is used as an animal model of p. vivax infection. this species' erythrocytes possess the duffy antigen and this antigen is used as the receptor for p. vivax on the erythrocytes in this species. examination of this gene in 497 patients in the amazonas state, brazil, made by the doctor sérgio albuquerque, suggests that the genotypes fy*a/fy*b-33 and fy*b/fy*b-33 (where -33 refers to the null mutation at position -33 in the gata box) may have an advantage over the genotypes fy*a/fy*b and fy*a/fy*a, fy*a/fy*b, fy*a/fy*x and fy*b/fy*x. fy*a/fy*b and fy*a/fy*a genotypes showed to be associated with increased rates of p. vivax infection and fy*b/fy*x and fy*a/fy*x were shown to be associated with the low levels of parasitism. a difference between the susceptibility to plasmodium vivax malaria has been reported. erythrocytes expressing fya had 41-50% lower binding of p. vivax compared with fyb cells. individuals with the fy(a+b-) phenotype have a 30-80% reduced risk of clinical vivax but not falciparum malaria. the binding of platelet factor 4 (cxcl4) appears to be critical for the platelet induced killing of p. falciparum. the duffy antigen binding protein in p. vivax is composed of three subdomains and is thought to function as a dimer. the critical darc binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. a study in brazil confirmed the protective effect of fy*a/fy*o against malaria. in contrast the genotype fy*b/fy*o was associated with a greater risk. asthma asthma is more common and tends to be more severe in those of african descent. there appears to be a correlation with both total ige levels and asthma and mutations in the duffy antigen. hematopoiesis duffy antigen plays a fundamental role on hematopoiesis. indeed, nucleated red blood cells present in the bone marrow have high expression of darc, which facilitates their direct contact with hematopoietic stem cells. the absence of erythroid darc alters hematopoiesis including stem and progenitor cells, which ultimately gives rise to phenotypically distinct neutrophils. as a result, mature neutrophils of duffy-negative individuals carry more molecular "weapons" against infectious pathogens. therefore, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of darc in the erythroid lineage. benign ethnic neutropenia a significant proportion (25–50%) of otherwise healthy african americans are known to have a persistently lower white blood cell count than the normal range defined for individuals of european ancestry—a condition known as benign ethnic neutropenia. this condition is also found in arab jordanians, black bedouin, beta israel, yemenite jews and west indians. this condition is associated with a reduced capacity to mobilize bone marrow neutrophil reserves in response to corticosteroids, despite normal cellularity and maturation of all cell lines in bone marrow aspirates. strongly suggestive evidence has been found that links condition to a mutation in the duffy gene. the distinctive neutrophils that are formed in the absence of darc on erythroid lineage (see above - role of darc on hematopoieisis) readily leave the blood stream, which explains the apparent lower numbers of neutrophils in the blood of duffy-negative individuals. cancer interactions between the metastasis suppressor kai1 on tumor cells and the cytokine receptor darc on adjacent vascular cells suppresses tumor metastasis. in human breast cancer samples low expression of the darc protein is significantly associated with estrogen receptor status, both lymph node and distant metastasis and poor survival. endotoxin response the procoagulant response to lipopolysaccharide (bacterial endotoxin) is reduced in duffy antigen negative africans compared with duffy positive whites. this difference is likely to involve additional genes. hiv infection a connection has been found between hiv susceptibility and the expression of the duffy antigen. the absence of the darc receptor appears to increase the susceptibility to infection by hiv. however once established, the absence of the darc receptor appears to slow down the progression of the disease. hiv-1 appears to be able to attach to erythrocytes via darc. the association between the duffy antigen and hiv infection appears to be complex. leukopenia (a low total white cell count) is associated with relatively poor survival in hiv infection and this association is more marked in whites than in people of black african descent, despite the (on average) lower white cell counts found in black africans. this difference appears to correlate with a particular genotype (-46c/c) associated with the absence of the duffy antigen. this genotype has only been found in black africans and their descendants. the strength of this association increases inversely with the total white cell count. the basis for this association is probably related to the role of the duffy antigen in cytokine binding but this has yet to be verified. a study of 142 black south african high-risk female sex workers over 2 years revealed a seroconversion rate of 19.0%. risk of seroconversion appeared to be correlated with duffy-null-associated low neutrophil counts. inflammation an association with the levels monocyte chemoattractant protein-1 has been reported. in the sardinian population, an association of several variants in the darc gene (coding and non-coding) correlates with increased serum levels of monocyte chemoattractant protein (mcp -1). a new variant in this population, consisting of the amino acid substitution of arginine for a cysteine at position 89 of the protein diminishes the ability to bind chemokines. darc has also been linked to rheumatoid arthritis (ra), possibly displaying chemokines such as cxcl5 on the surface of endothelial cells within the synovium, increasing the recruitment of neutrophils in the disease state. lung transplantation the duffy antigen has been implicated in lung transplantation rejection. multiple myeloma an increased incidence of duffy antigen has been reported in patients with multiple myeloma compared with healthy controls. pneumonia the duffy antigen is present in the normal pulmonary vascular bed. its expression is increased in the vascular beds and alveolar septa of the lung parenchyma during suppurative pneumonia. pregnancy duffy antigen has been implicated in haemolytic disease of the newborn. prostate cancer experimental work has suggested that darc expression inhibits prostate tumor growth. men of black african descent are at greater risk of prostate cancer than are men of either european or asian descendant (60% greater incidence and double the mortality compared to whites). however, the contribution of darc to this increased risk has been tested in jamaican males of black african descent. it was found that none of the increased risk could be attributed to the darc gene. the reason for this increased risk is as yet unknown. psychiatry the use of the antipsychotic agent clozapine is associated with neutropenia. an increased risk of this side effect has been reported in duffy null patients. renal transplantion antibodies and a cellular response to the duffy antigen have been associated with renal transplant rejection. sickle cell anaemia duffy antigen-negative individuals with sickle cell anaemia tend to sustain more severe organ damage than do those with the duffy antigen. duffy-positive patients exhibit higher counts of white blood cells, polynuclear neutrophils, higher plasma levels of il-8 and rantes than duffy-negative patients. southeast asian ovalocytosis there is a ~10% increase in fy expression in southeast asian ovalocytosis erythrocytes. transfusion medicine interpretation of antibody panel to detect patient antibodies towards the most relevant human blood group systems, including duffy. further information: blood compatibility testing a duffy negative blood recipient may have a transfusion reaction if the donor is duffy positive. since most duffy-negative people are of african descent, blood donations from people of black african origin are important to transfusion banks. transfusion data international society for blood transfusion (isbt) symbol: fy isbt number: 008 gene symbol: fy gene name: duffy blood group number of duffy antigens: 6 antibody type almost entirely igg. igg1 usually predominates. igm does occur but is rare. antibody behavior anti-fya is a common antibody while anti-fyb is approximately 20 times less common., they are reactive at body temperature and are therefore clinically significant, although they do not typically bind complement. antibodies are acquired through exposure (pregnancy or history of blood transfusion) and