The BloodGen project: toward mass‐scale comprehensive genotyping of blood donors in the European Union and beyond

Avent, Neil D.; Martínez, Antonio; Flegel, Willy A.; Olsson, Martin L.; Scott, Marion L.; Nogués, Núria; Pı́sačka, Martin; Daniels, Geoff; Schoot, Ellen van der; Muñiz‐Díaz, Eduardo; Madgett, Tracey E.; Storry, Jill R.; Beiboer, Sigrid H.W.; Wijk, Petra A. Maaskant‐van; Zabern, Inge von; Jiménez, Elisa; Tejedor, Diego; López, Mónica; Camacho, Emma; Cheroutre, Goedele; Hacker, Anita; Jinoch, Pavel; Svobodová, Irena; Haas, Masja de

doi:10.1111/j.1537-2995.2007.01309.x

Cited by 70 publications

(68 citation statements)

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“…Now that almost all the blood group genes have been cloned and the molecular bases of most antigens determined, it is feasible to conduct such a study with the use of high-throughput DNA-based methods. [122][123][124][125] Furthermore, the availability of rapid DNA sequencing methodologies presages an era in which mass screening of genes encoding red cell membrane proteins could be used to identify new polymorphisms of relevance to malarial invasion. Studies of this type, focused in tropical Africa, South East Asia, and Latin America, would provide a valuable database of new information about blood group diversity in populations inhabiting these regions not only for malarial epidemiologists but also for those investigating human susceptibility to new emerging infectious diseases given that zoonoses from wildlife in these regions have been identified as the most significant growing threat to global health of all emerging infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

377

349

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The relative contribution of founder effects and natural selection to the observed distribution of human blood groups has been debated since blood group frequencies were shown to differ between populations almost a century ago. Advances in our understanding of the migration patterns of early humans from Africa to populate the rest of the world obtained through the use of Y chromosome and mtDNA markers do much to inform this debate. There are clear examples of protection against infectious diseases from inheritance of polymorphisms in genes encoding and regulating the expression of ABH and Lewis antigens in bodily secretions particularly in respect of Helicobacter pylori, norovirus, and cholera infections. However, available evidence suggests surviving malaria is the most significant selective force affecting the expression of blood groups. IntroductionHirszfeld and Hirszfeld 1 showed the frequencies of blood groups A and B differ between populations. Their observations raised fundamental questions regarding the causes of these differences, which were eloquently summarized by Mourant et al 2(p1) :Were the differences the result of random genetic drift and founder effects, in small populations which later multiplied and stabilized the original, fortuitous, frequencies, or were they the result of natural selection, arising from differences in fitness between the various blood groups, fitnesses which themselves depended upon locally determined features of the external environment?Mourant et al concluded that "most workers now agree that both processes are operative, but their relative importance remains in question." 2 We now have detailed information concerning almost all the genes giving rise to blood group polymorphisms, the structure of the gene products and the antigens themselves, and in many cases functional information sufficient to delineate mechanisms of interaction with external agents. [3][4][5] In addition, studies on the tracking of Y chromosome and mtDNA haplotypes in human populations provide us with unprecedented information concerning the significance of genetic drift and founder effects in determining the genetic background of different world populations. 6 Given this new information, it seems an appropriate time to revisit these questions and ask whether we are any nearer understanding the relative importance of natural selection and founder effects in determining the distribution of human blood groups. Infectious diseases and selection for ABO blood group antigensThe molecular basis of the ABO blood group system was elucidated in 1990. 7 The gene encodes a glycosyltransferase, which transfers N-acetyl D-galactosamine (group A) or D-galactose (group B) to the nonreducing ends of glycans on glycoproteins and glycolipids. The group O phenotype results from inactivation of the A1 glycosyltransferase gene, and the nonreducing ends of the corresponding glycans in group O subjects express the blood group H antigen ( Figure 1A). The ABH antigens are not confined to red cells but are widely expressed i...

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Section: Discussionmentioning

confidence: 99%

The relationship between blood groups and disease

Anstee

2010

Blood

377

349

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“…An automated test platform developed in Europe (BLOODChip, Progenika Biopharma S.A.) is now available in the United States; in addition to minor blood group antigens it includes an extensive number of variant RHD alleles. 36 SNPs associated with variant expression of C/c and E/e antigen are also under development by this manufacturer (personal communication).…”

Section: Rh Genotypingmentioning

confidence: 99%

Molecular biology of the Rh system: clinical considerations for transfusion in sickle cell disease

Chou

Westhoff²

2009

Hematology

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The last decade has witnessed an abundance of information detailing the genetic diversity of the RH locus which has exceeded all estimates predicted by serology. Well over 120 RHD and over 60 different RHCE alleles have been documented, and new alleles are still being discovered. For clinical transfusion medicine, RH genetic testing can now be used to determine RHD zygosity, resolve D antigen status, and detect altered RHD and RHCE genes in individuals at risk for producing antibodies to high-incidence Rh antigens, particularly patients with sickle cell disease (SCD).T ransfusion of patients with sickle cell disease (SCD) represents a significant challenge in clinical transfusion medicine with red blood cell (RBC) alloimmunization a primary and serious complication of transfusions. A major cause of alloimmunization in patients with SCD is the disparate distribution of red cell antigens between donors, who are primarily of European ancestry, and patients with SCD, who are primarily of African ancestry. Management of alloimmunization in SCD has been the subject of much debate, 1,2 and currently there is no standard approach. Over two thirds of alloantibodies formed by patients with SCD have Rh blood group specificities. Many programs transfuse patients with SCD with RBCs that are phenotype-matched for D, C/c, E/e, and K, and some also supply RBCs from African-American donors when possible. Although these approaches reduce the incidence of alloantibody production, patients still become alloimmunized. Genetic analysis of patients who develop antibodies in the face of conventional antigen matching has revealed that these patients carry altered RH alleles. RH Genes and Rh ProteinsTwo genes, RHD and RHCE, lie in close proximity on chromosome 1 and encode 416-amino acid Rh proteins: one encodes the D antigen, and the other encodes CE antigens in various combinations (ce, cE, Ce, or CE) (Figure 1). Each gene has ten exons; they are 97% identical and encode proteins that differ by 32 to 35 amino acids (Figure 1). This contrasts with most blood group antigens, which are encoded by single genes with alleles that differ TRANSFUSION MEDICINE ___________________________________________________________________________________ by only one or a few amino acids. For comprehensive reviews, see Westhoff 3 and Avent. The conventional RH genes shown in Figure 1 are found in all population groups, although with different frequencies. Commercial antibody reagents detect expression of the five principal Rh antigens: D, C, c, E, and e. Variant RHD and RHCE alleles encode Rh proteins with amino acid changes that cannot be distinguished serologically, but can be recognized by the immune system as foreign. Of relevance for transfusion in patients with SCD, RH alleles encoding altered C and e antigens are frequent in African ethnic groups. 5,6 Some patients with SCD are at risk for production of antibodies to both the RhCE and RhD proteins, a serious and potentially life-threatening complication. Variations of RhD

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“…Patient A's sample was typed by serology as Fy (a-b-) which is very rare in Europeans but common in West Africans. 48 Subsequent molecular investigations, using allele-specific primers 49,50 and the blood group genotyping system BLOODchip, 42,51 demonstrated that patient A has the rare FY*0/FY*X genotype which predicts weakened Fy b antigen expression on erythrocytes. This weakened antigen expression, coupled with hemizygosity for the FY*B allele, made serological detection of the Fy b antigen very difficult and could have led to the erroneous interpretation that the Duffy antigen was diminished, as is the case in the 4.1R(-) mouse.…”

Section: Blood Group Antigen Expression On 41r(-) Erythrocytesmentioning

confidence: 99%

“…DNA quality control thresholds were set at a minimum concentration of 40 ng/µL and an A260/A280 ratio of between 1.6 and 1.95. BLOODchip multiplex polymerase chain reactions (PCR) (Progenika Biopharma, S.A., Derio, Spain) were carried out using 42 The PCR products were amplified in a uniform manner by the inclusion of multiplex-amplifiable probe hybridization tag binding sites on the 5' ends of most of the primers. 43 The technical approach adopted by allele-specific hybridization DNA Array Methodology has been described by Tejedor et al.…”

Section: Blood Group Genotyping Using Bloodchipmentioning

confidence: 99%

4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

Jeremy¹,

Plummer²,

Head³

et al. 2009

Haematologica

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BackgroundProtein 4.1R is an important component of the red cell membrane skeleton. It imparts structural integrity and has transmembrane signaling roles by direct interactions with transmembrane proteins and other membrane skeletal components, notably p55 and calmodulin. Design and MethodsSpontaneous and ligation-induced phosphatidylserine exposure on erythrocytes from two patients with 4.1R deficiency were studied, using CD47 glycoprotein and glycophorin C as ligands. We also looked for protein abnormalities in the 4.1R -based multiprotein complex. ResultsPhosphatidylserine exposure was significantly increased in 4.1R-deficient erythrocytes obtained from the two different individuals when ligands to CD47 glycoprotein were bound. Spontaneous phosphatidylserine exposure was normal. 4.1R, glycophorin C and p55 were missing or sharply reduced. Furthermore there was an alteration or deficiency of CD47 glycoprotein and a lack of CD44 glycoprotein. Based on a recent study in 4.1R-deficient mice, we found that there are clear functional differences between interactions of human red cell 4.1R and its murine counterpart. ConclusionsGlycophorin C is known to bind 4.1R, and we have defined previously that it also binds CD47. From our evidence, we suggest that 4.1R plays a role in the phosphatidylserine exposure signaling pathway that is of fundamental importance in red cell turnover. The linkage of CD44 to 4.1R may be relevant to this process. CD44 and CD47 glycoproteins. Haematologica 2009;94:1354-1361. doi:10.3324/haematol.2009 This is an open-access paper. 4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

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The BloodGen project: toward mass‐scale comprehensive genotyping of blood donors in the European Union and beyond

Cited by 70 publications

References 69 publications

The relationship between blood groups and disease

The relationship between blood groups and disease

Molecular biology of the Rh system: clinical considerations for transfusion in sickle cell disease

4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

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