Blood Group Polymorphisms Research Articles

Anthropology and Genetics of the Caucasus Peoples and the Problem of the Origin of the Caucasoids

The electrophoretical polymorphisms of some blood proteins were studied in the Talysh population of Pirasora situated in South-East Azerbaidjan. We calculated the gene frequencies of these polymorphisms and determined the genetic distances between the Talyshes and some Iranian populations of North, Central and South Iran, Afghans, and three populations of Azerbaijan. The Talyshes are very close to Iranians of Shiraz, whereas they are distant from the Azerbaijanians. Anthropological investigations showed that the Caucasoids and Mongoloids lived in the Aragvi Basin since the Eneolithic period. This was stated by Alexeev (1974), who emphasized the mixture of the Caucasus populations from ancient times on. We calculated the genetic distances between the Caucasus populations and numerous populations of other geographic regions, considering 28 alleles of 12 loci of blood group, serum protein and red cell enzyme polymorphisms and constructed the dendrogram of these populations. The position of the Caucasus populations in the dendrogram corresponds on principle to the earlier anthropological observations. The clustering of the Caucasoid populations corresponds completely with anthropological and historical data, and supports our earlier hypothesis (Nazarova 1999) concerning the differentiation of Caucasoids, Northern Mongoloids and Amerinds from the populations, which inhabitated Asia in palaeolithic times.

Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region

BackgroundDuffy blood group polymorphisms are important in areas where Plasmodium vivax predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in P. vivax malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria.MethodsThe P. vivax identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used.ResultsThe data show a high frequency of the FYA/FYB genotype, followed by FYB/FYB, FYA/FYA, FYA/FYB-33 and FYB/FYB-33. Low frequencies were detected for the FYA/FYX, FYB/FYX, FYX/FYX and FYB-33/FYB-33 genotypes. Negative Duffy genotype (FYB-33/FYB-33) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the FYX/FYB-33 genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients.ConclusionThe obtained data suggest that individuals with the FYA/FYB genotype have higher susceptibility to malaria. The presence of the FYB-33 allele may be a selective advantage in the population, reducing the rate of infection by P. vivax in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for P. vivax malaria, in particular the Brazilian Amazon region.

Invasion of Rh Null Cells by Plasmodium falciparum identifies a new invasion pathway

The malaria parasite, Plasmodium falciparum, invades the human erythrocyte through a complex interaction with erythrocyte receptors characterized by patterns of resistance to various enzymes. As invasion rates are influenced by blood group polymorphisms, we reasoned that the extremely rare rhesus null (Rh(null)) erythrocytes could be informative in characterizing receptors. The aim was to test whether the complete absence of the Rh complex from the cell membrane impacted on parasite invasion. Enzyme treatment patterns for four P. falciparum isolates were first characterised for normal Rh cells. Two isolates showed an enzyme treatment pattern not hitherto described, with resistance to neuraminidase, trypsin and chymotrypsin. In contrast, all isolates had enhanced invasion rates for the Rh(null) cell for all enzyme treatment regimens. The first finding suggests there is another pathway that P. falciparum can utilise to invade the host. We speculate that the Rh null cell membrane exposes a novel ligand defined as Receptor N.

Modeling the structure of supergenes controlling some polyallelic blood group systems in the pig Sus scrofa and horse Equus caballus

Two polymorphic blood group systems (E and M) of the pig Sus scrofa L. and one blood group system (D) of the horse Equus caballus L. have been studied. On the basis of phenogroup analysis, models describing the formation of the complex allele spectra of these systems and reflecting the contributions of mutations and recombinations have been constructed. The complementary relationships between the antigens determined by the variants of supergenes within the systems, as ell as the probable number and relative positions of the subloci encoding individual groups of antigens in them, have been determined.

Improving minority blood donation: anthropologic approach in a migrant community

As a result of blood group polymorphism, distinctive blood types have evolved in populations around the world. In countries with large migrant populations, finding rare blood types for transfusion can be challenging. This is especially true for sub-Saharan African immigrants living in countries with predominantly European populations. This problem is further compounded by hereditary disorders such as sickle cell disease and by traditional cultural values that discourage routine donation. The purpose of this report is to describe the drive to recruit more safe rare blood type donors in a Comorian immigrant community living in Marseilles, France. With a culturally adapted message developed on an anthropologic approach and working in close collaboration with scientific and medical members of the Comorian community, it is proposed that this population be sensitized with the gift of blood. Targeted collection of specific sub-Saharan African blood types was achieved. Taking into account the high rate of infectious markers among products collected in this targeted collection, however, it was decided to promote blood donation in this minority by addressing people directly toward our principal blood center site. Since setup of this adapted communication, regular donors present themselves spontaneously without community pressure. Infectious markers rate is then equal to general blood donor population's rate. The results of this drive demonstrate the utility of an anthropologic approach and cultural mediation in identifying donors with specific blood types in migrant communities and recruiting second-generation donors. The techniques described in this study could also be applied to collection of other tissues including organs and peripheral blood progenitor cells in minorities.

Influence of ABO blood group polymorphism on mortality in intensive care unit patients

Blood groups may be related to differences in inflammatory responses [1]. We looked at blood group as a risk factor for ICU mortality in general and for patients with sepsis.

Prevalence of RHD 1227A and hybrid Rhesus box in the general Chinese population

The Rhesus (Rh) blood group is the most polymorphic blood group system. Serological analyses revealed that only 0.1% to 0.4% of the Chinese population exhibited a D-negative phenotype. In contrast to D-negative Caucasian persons, who are mostly associated with a deletion of RHD between the upstream and downstream Rhesus boxes, approximately 30% of apparently D-negative Chinese were actually DEL, potentially harboring a grossly intact RHD gene. The authors' previous detection of the RHD 1227A allele in all DEL samples prompted the conclusion that the RHD 1227A gene is highly prevalent in DEL populations of Chinese ethnicity, which indicates that it may be a marker for the rapid detection of DEL. Currently, random surveys for RHD 1227 A allele and for hybrid Rhesus box were conducted among 399 Han Chinese in Taiwan. The estimated frequencies of RHD 1227G/G, RHD 1227A/G, RHD A/A, RHD 1227G/-, RHD 1227A/-, and RHD-/- were 0.89054, 0.0118, 0.00016, 0.0414, 0.00055, and 0.00192, respectively. These results were consistent with the prevalence of D-negative and DEL in persons of Chinese ethnicity. The authors conclude that detection of RHD 1227A and hybrid Rhesus box alleles is predictive of Rh phenotypes in the Chinese population.

A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen

The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents. Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression. RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes. Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.

SI35 Blood Group Antigen Typing Using DNA Microarray BeadChipsTM–First UK Report

Background The determination of human blood group phenotypes has routinely involved red cell agglutination techniques. The genes for all but one of the 29 human blood group systems have now been cloned and the molecular bases of all clinically significant blood group polymorphisms are known. Consequently these DNA sequences can be used to predict blood group phenotypes. Molecular typing as an adjunct to serology offers improved accuracy and can save both rare reagents and laboratory time while screening for compatible donor units. This study determined the feasibility of analysis of single nucleotide polymorphisms (SNPs) associated with a variety of blood group antigens using a DNA microarray system with a beadchip technology platform.Method SNPs were tested by elongation‐mediated analysis of polymorphisms (eMAPTM) using allele‐specific oligonucleotides with variable 3’‐terminal sequences attached to colour‐encoded beads. The beads are assembled into arrays on semiconductor chips (BeadChipTM), available from Bioarray Solutions. Elongation products for SNPs or small deletions/insertions were simultaneously detected by instant imaging of fluorescence signals from the entire array. Seventeen polymorphisms associated with Human Erythrocyte Antigens and one mutation associated with hemoglobinopathies (CO, DI, DO, FY, JK, KEL, LU, LW, MNS, SC and HgbS) were included in the HEA BeadChipTM Kit.Results The system was validated using a reference DNA panel of known phenotype (n = 30) and genotype, established by conventional DNA‐PCR SSP assays. Replicate testing (n = 6 reps for eight samples) gave 100% consistent data demonstrating the Bioarray system to be both reliable and reproducible. The initial concordance rate with serology was 99.2%.Conclusion The BeadChip System represents the first integrated flexible array solution for high complexity transfusion testing, accommodating ‘multiplex’ analysis of polymorphisms. This high throughput, microarray system offers the potential to determine extended genotypes of patients and maintain an extended‐genotype, national panel of donors to provide compatible blood for sensitised patients. The initial high concordance rate and the rarity of CE marked phenotyping reagents justifies its further development.

ABO phenotypes and malaria related outcomes in mothers and babies in The Gambia: a role for histo-blood groups in placental malaria?

BackgroundHost susceptibility to P.falciparum is critical for understanding malaria in pregnancy, its consequences for the mother and baby, and for improving malaria control in pregnant women. Yet host genetic factors which could influence placental malaria risk are little studied and there are no reports of the role of blood group polymorphisms on pregnancy outcomes in malaria endemic areas.This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology.MethodsA total of 198 mother/child pairs delivering in Banjul and the Kombo-St Mary District (The Gambia) were analysed. ABO blood group was measured by agglutination. Placental malaria parasites wee enumerated and the presence of malaria pigment noted. Birth anthropometry was recorded and placental weight. Maternal and infant haemoglobin was measured.Results89 (45%) subjects were primiparae and 110 (55%)multiparae. The ABO phenotype distribution was 38(A), 52(B), 6(AB) and 102(O). Placental histo-pathology showed active placental malaria in 74 (37%), past infection in 42 (21%) and no infection in 82 cases (41%). In primiparae blood group O was associated with a higher risk of active infection (OR = 2.99; 95% CI = 1.24–7.25), and a lower risk of past infection (OR = 0.31, 0.10–1.01, p < 0.05). In multiparae the O phenotype was associated with reduced prevalence of active or past placental infection (OR = 0.45; 95% CI 0.21–0.98). The mean feto-placental weight ratio was significantly higher in multiparae with group O women compared to non-O phenotypes (5.74 vs 5.36; p = 0.04). Among primiparae with active placental infection, mean birth weight was higher in children of mothers with the O phenotype (p = 0.04).ConclusionThese results indicate that blood group O was significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae. This parity related susceptibility was not present with other ABO phenotypes. Cell surface glycans, such as ABO and related antigens have special relevance in reproductive biology and could modulate specific cell interactions as those associated with the pathogenesis of placental malaria.

Structure and function of red cell surface antigens

Currently there are almost 300 red cell surface antigenic determinants or blood group specificities recognized by the International Society of Blood Transfusion; most of these belong to 1 of 29 blood group systems. Each system represents a single gene or cluster of 2 or 3 closely linked homologous genes, giving a total of 34 gene loci. Each of these genes has been cloned and sequenced, with the exception of one, P , and there is a candidate gene for this. Consequently, we have a tremendous amount of structural information about the red cell surface. Despite this, there is still much we do not know about the functions of these antigens; much of what we do know has been deduced from their structures. We know almost nothing about the functions of the blood group polymorphisms. The blood group systems are listed in Table 1, with information on the structures of their antigens and their possible functions. Almost all blood group systems have a null phenotype, in which no antigen of that system is expressed on the red cells. Null phenotypes are generally rare. They are usually only found when individuals with these phenotypes may make antibodies to the missing proteins following immunization by blood transfusion or pregnancy. Such antibodies are then identified in immunohaematology reference laboratories. Null phenotypes usually result from homozygosity for inactivating mutations or even a gene deletion, so the whole protein is absent from the red cells and from everywhere else in the body, at any stage of development. Yet in many cases individuals with these rare phenotypes are apparently healthy. This reflects the functional redundancy of many cell surface proteins. Often, when one protein is missing, another can perform the same function in its absence. However, this is not always the case and null phenotypes have been very informative about the functions of blood group antigens both on red cells and in other tissues. Red cell surface antigens are macromolecules anchored in the lipid bilayer of the red cell envelope. There are three main types of macromolecules expressing blood group activity: proteins, glycoproteins, and glycolipids. Most blood group antigens are glycoproteins, with the specificity determined primarily either by the oligosaccharide sequence (e.g. ABO) or by the amino acid sequence (e.g. MN, Kell, Duffy, Kidd, Diego). The Rh antigens are non-glycosylated proteins, though the presence of an associated glycoprotein is required for antigenic expression. ABO antigens are also expressed on the carbohydrate moiety of glycosphingolipids. In this article red cell surface antigens will be discussed in terms of their functions or potential functions, under the following five headings: transporters and channels; receptors and adhesion molecules; enzymes; structural proteins that link the lipid bilayer to the membrane skeleton; and those structures that contribute to the glycocalyx, or cell coat.

Testing for rare blood donors by DNA analysis

Alloantibodies to blood group antigens are produced because there are differences between the blood group antigens on recipient and donor red blood cells. Historically, and currently, blood group antibodies and antigens are detected by haemagglutination, which requires appropriate reagents and considerable skill. Over the past two decades there has been an astounding pace of growth in the field of molecular biology techniques and even more recently in the understanding of the basis of many blood group antigens and phenotypes. Thus, we are now able to determine blood group polymorphisms and predict blood group antigen expression using molecular approaches. This article reviews molecular approaches to identify donors with rare blood types, either due to the absence of a high prevalence antigen or an absence of a combination of antigens.

Blood group and serum protein polymorphisms in a population group of Moldavians

The distribution of the alleles and haplotypes for blood groups A1A2B0, MNSs, RHESUS, P1, KELL-CELLANO and biochemical markers of the alleles of loci AMY2, HPA, GC, C3, TF, BF, CP, PI (including subtypes) were studied in 125 Moldavian individuals from Karahasani settlement, Stefan-Voda District, Republic of Moldavia. The results show that the gene pool of Moldavians is similar to those of Southeastern European populations.

혈액형에 의한 제주말의 유전적 다형성 분석

제주말의 혈통보존을 위한 기초자료를 마련할 목적으로 국내에서 사육중인 제주말 102두를 대상으로 적혈구항원형 및 혈액단백질형의 유전적 다형성을 조사한 결과는 다음과 같다. 적혈구항원형의 표현형 빈도는 <TEX>$A^{af}$</TEX>28두(<TEX>$27.45\%),\;C^{a}$</TEX> 101두 (<TEX>$99.02\%),\;K^{-}$</TEX> 99두 (<TEX>$97.06\%),\;U^{a}$</TEX> 64두 (<TEX>$62.75\%),\;P^{b}$</TEX> 37두 (<TEX>$36.27\%),\;Q^{c}$</TEX> 48두 (<TEX>$47.06\%$</TEX>)에서 높은 빈도를 나타냈으며, D시스템의 31개의 대립유전자 중 <TEX>$D^{cgm/dghm}$</TEX> 14두(<TEX>$13.73\%),\;D^{adn/cgm}$</TEX> 10두(<TEX>$9.80\%),\;D^{ad/cgm}$</TEX> 9두(<TEX>$8.82\%),\;D^{dghm/dghm}$</TEX> 8두(<TEX>$7.84\%),\;D^{cgm/cgm}$</TEX> 8두(<TEX>$7.84\%$</TEX>)에서 높은 빈도의 유전자형이 관찰되었다. 또한 null allele로 추정되는 <TEX>$D^{ad/c(e)fgm}\;D^{adn/c(e)fgm}\;D^{c(d)fgm/dghm}$</TEX>대립유전자가 4두에서 관찰되었다. 혈액단백질형은 <TEX>$AL^{B}$</TEX> 49두(<TEX>$48.04\%),\;GC^{F}$</TEX> 101두(<TEX>$99.02\%),\;AlB^{K}$</TEX> 99두(<TEX>$97.06\%),\;ES^{FI}$</TEX> 37두(<TEX>$36.27\%),\;TF^{F2}$</TEX> 26두(<TEX>$25.49\%),\;HB^{B1}$</TEX> 46두(<TEX>$45.10\%$</TEX>), and <TEX>$PGD^{F}$</TEX> 88두(<TEX>$86.27\%$</TEX>)로 높은 빈도를 보였으며, <TEX>$HB^{A2B1}$</TEX> 4두(<TEX>$3.92\%),\;HB^{AB1}$</TEX> 2두(<TEX>$1.96\%),\;HB^{AB2}$</TEX> 1두(<TEX>$0.98\%),\;PGD^{D}$</TEX> 1두(<TEX>$0.98\%$</TEX>가 특이하게 관찰되었다. 유전자 빈도는 <TEX>$A^{af}$</TEX> (0.3726), <TEX>$A^{C}$</TEX> (0.2647), <TEX>$C^{-}$</TEX> (0.5050), <TEX>$K^{-}$</TEX> (0.9853), <TEX>$U^{-}$</TEX> (0.6863), <TEX>$P^{b}$</TEX> (0.4657), <TEX>$Q^{c}$</TEX> (0.5294), <TEX>$D^{cgm}$</TEX> (0.3039), <TEX>$HB^{B1}$</TEX>(0.6863), <TEX>$PGD^{F}$</TEX> (0.9265), <TEX>$AL^{B}$</TEX> (0.6912), <TEX>$ALB^{K}$</TEX> (0.9852), <TEX>$GC^{F}$</TEX> (0.9950), <TEX>$ES^{I}$</TEX> (0.5000) and <TEX>$TF^{F2}$</TEX> (0.4950) 대립유전자가 가장 높은 빈도를 나타내었고 <TEX>$D^{cgm(f)}$</TEX> (0.0196), <TEX>$HB^{A}$</TEX> (0.0147), <TEX>$HB^{A2}$</TEX> (0.0196), <TEX>$ES^{G}$</TEX> (0.0441), <TEX>$ES^{H}$</TEX> (0.0098), <TEX>$TF^{E}$</TEX>TF'(0.0246), <TEX>$TF^{H2}$</TEX> (0.0049) and <TEX>$PGD^{D}$</TEX> (0.0098)의 대립유전자가 제주말 에서 특이하게 관찰되었다. 결론적으로 혈액형에 의한 제주말의 유전적 다형은 <TEX>$A^{af},\;A^{c},\;C^{-},\;K^{-},\;U^{-},\;P^{b},\;Q^{c},\;D^{cgm},\;D^{dghm},\;D^{adn},\;HB^{B1}$</TEX>, <TEX>$PGD^{F},\;AL^{B},\;A1B^{K},\;GC^{F},\;ES^{I},\;TF^{F2},\;AL^{B}$</TEX>, 대립유전자의 빈도가 비교적 높은 것으로 관찰되었고 <TEX>$A^{ab},\;A^{abf},\;D^{cgm(f)},\;(D^{cfg(k)m}$</TEX> 혹은<TEX>$D^{c(e)fgm}),\;HB^{A},\;HB^{A2},\;ES^{H},\;TF^{E},\;TF^{H2},\;PGD^{D},\;AL^{B}$</TEX>의 대립유전자가 제주말에서 특이하게 관찰되었다. The present study was carried out to investigate the blood markers of Jeju horses. The redcell cypes (blood groups) and blood protein types (biochemical polymorphisms) were tested from 102 Jeju horses by serological and electrophoretc procedure, and their phenotypes and gene frequencies were estimated. The blood group and biochemical polymorphism phenotypes observed with high frequency were <TEX>$A^{af}\;(27.45\%$</TEX>), <TEX>$C^{a}\;(99.02\%$</TEX>), <TEX>$K^{-}\;(97.06\%$</TEX>), <TEX>$U^{a}\;(62.75\%$</TEX>), <TEX>$P^{b}\;(36.27\%$</TEX>), <TEX>$Q^{c}\;(47.06\%$</TEX>), <TEX>$D^{cgm/dghm}\;(13.73\%$</TEX>), <TEX>$D^{adn/cgm}\;(9.80\%$</TEX>), <TEX>$D^{ad/cgm}$\;(8.82\%$</TEX>), <TEX>$D^{dghm/dghm}(7.84\%$</TEX>), <TEX>$D^{cgm/cgm}(7.84\%$</TEX>), <TEX>$AL^{B}\;(48.04\%$</TEX>), <TEX>$GC^{F}\;(99.02\%$</TEX>), <TEX>$AlB^{K}\;(97.06\%$</TEX>), <TEX>$ES^{FI}\;(36.27\%$</TEX>), <TEX>$TF^{F2}\;(25.49\%$</TEX>), <TEX>$HB^{B1}\;(45.10\%$</TEX>), and <TEX>$PGD^{F}\;(86.27\%$</TEX>) in Jeju horses, respectively. Alleles observed with high gene frequency were <TEX>$A^{af}$</TEX> (0.3726), <TEX>$A^{C}$</TEX> (0.2647), <TEX>$C^{-}$</TEX> (0.5050), <TEX>$K^{-}$</TEX> (0.9853), <TEX>$U^{-}$</TEX> (0.6863), <TEX>$P^{b}$</TEX> (0.4657), <TEX>$Q^{c}$</TEX> (0.5294), <TEX>$D^{cgm}$</TEX> (0.3039), <TEX>$HB^{B1}$</TEX>(0.6863), <TEX>$PGD^{F}$</TEX> (0.9265), <TEX>$AL^{B}$</TEX> (0.6912), <TEX>$ALB^{K}$</TEX> (0.9852), <TEX>$GC^{F}$</TEX> (0.9950), <TEX>$ES^{I}$</TEX> (0.5000) and <TEX>$TF^{F2}$</TEX> (0.4950) in Jeju horses, and sfecific alleles, <TEX>$D^{cgm(f)}$</TEX> (0.0196), <TEX>$HB^{A}$</TEX> (0.0147), <TEX>$HB^{A2}$</TEX> (0.0196), <TEX>$ES^{G}$</TEX> (0.0441), <TEX>$ES^{H}$</TEX> (0.0098), <TEX>$TF^{E}$</TEX>TF'(0.0246), <TEX>$TF^{H2}$</TEX> (0.0049) and <TEX>$PGD^{D}$</TEX> (0.0098) were detected in Jeju horses. These preliminary results present basic information for detecting the genetic markers in Jeju horse. and developing a system for parentage verification and individuals identification in jeju horses.

High-Throughput DNA Analysis for Red Blood Cell Antigens Facilitates the Transfusion Support with Antigen-Matched Blood in Sickle Cell Disease Patients.

Background: Transfusion dependent patients as those with Sickle Cell Disease (SCD) patients become alloimmunized and have the potential to form additional antibodies with such frequency that antigen-negative blood is preferred to prevent further alloimmunization. Blood group genotyping is playing a supporting role in the routine blood banks, especially for provision of antigen-matched blood for these patients. However, current techniques for genomic typing are all labor-intensive and require manual set up and analysis by gel electrophoresis. As a result, DNA microarrays are being developed for the single nucleotide polymorphisms (SNPs) detection in the blood group genes to provide a fast procedure and an automated analysis of numerous blood group polymorphisms. We evaluated the usefulness of DNA microarray to provide a means to precisely match donor blood to the antigen-negative type of SCD patients. Method: A total of 12 DNA samples from patients with SCD (homozygous for HbS) and 84 DNA samples from blood donors, were analyzed by the HEA Beadchip (Hashmi et al, 2005) containing a total of 18 SNPs (FYA/B, FY-GATA, FY265, DOA/B (nt 378, 624, 793), COA/B, LWA/B, DIA/B, SC1/SC2, M/N, S/s, LUA/B, KEL1/2, JKA/B, DO323, DO350, HgbS) in a single reaction. Results: A genotype result was obtained for all SNPs tested on 96 samples within 4 hours of the start of testing. Results obtained by Beadchip analysis in donors were used to provide antigen-matched blood for FYA/B, FY-GATA, FY265, DOA/B, M/N, S/s KEL1/2, JKA/B, for all 12 SCD patients. This technology provided a fast procedure and facilitated the transfusion support with antigen-matched blood in SCD patients allowing the reduction of alloimunization to blood group antigens. Conclusion: This high-throughput DNA analysis has the potential not only to increase the inventory of antigen-negative blood but also to facilitate the matching of RBC component to the recipient's blood type. It also contributes to the management of transfusions in SCD patients by allowing a more accurate selection of donor units. The application of microarray technology in transfusion medicine may have a tremendous impact on further improvement of the safety of blood transfusion.

Ss Polymorphisms Carried on GPB in Brazilian Malaria Infected and Non-Infected Individuals.

Background: The present study was carried out to compare the Ss blood group polymorphisms carried on GPB in patients infected by malaria (n=51–100) with blood donors (n=100–170) living under the same conditions in a malaria endemic region of the Brazilian Amazon (Macapá, Belém, Porto Velho and Rio Branco). The blood donors had no clinical signs for malaria, their thick blood film exam was negative and they reported during the interview that they had no prior episodes of malaria.Methods: Blood donors and individuals having only P. falciparum infected were identified and their blood was used for Ss phenotyping in gel cards (DiaMed-AG) and to prepare DNA for Ss genotyping and associations studies. The Ss polymorphisms were genotyped by allele-specific (AS)-PCR.Results: Comparison between the frequencies of the Ss phenotypes/genotypes in the two studied groups in each endemic area showed a significant correlation between the frequency of individual carrying the S+s+ or S+s- phenotypes/genotypes and incidence of malaria infection in three regions of the study; Rio Branco, Porto Velho and Belem. The presence of the S antigen was significantly more frequent in malaria patients when compared with the blood donors in three regions of the study; Rio Branco (60.8 vs. 38%), Porto Velho (53.1 vs. 38%) and Belem (62 vs. 50%). As a confirmation, we also found that the S-s+ phenotype in the three regions was contributing to resistance to infection with malaria, as it was significantly more frequent in the donor population than in infected individuals. Importantly, there are approximately 1.5 times more copies of GPB in S+s- than in S-s+ RBCs. S+s+ RBCs have an intermediate amount of GPB. When we combined the results from the four regions and analyzed the 64 P. falciparum (Pf) positive individuals vs. the total 63 blood donors, 46 P. falciparum positive individuals (71.8%) carried the S+ phenotype on the GPB whereas in normal donor population only 30 individuals (47.6%) carried the S antigen.. In this analysis, the presence of the S antigen was significantly more frequent in the P. falciparum patients when compared with the blood donors (P = 0.006). Conversely, the S-s+ phenotype in the four regions was contributing to resistance to P. falciparum infection, as it was significantly more frequent in the donor population (52.3%) than in infected individuals (28.1%).Conclusion: These results support the hypothesis that the expression of the S antigen on GPB is associated not only with incidence of malaria infection, but more importantly, with incidence of P. falciparum infection. These preliminary results open up the opportunity to study the utilization of the GPB invasion pathway, in particular via a domain that contains the S antigen, by the P. falciparum field isolates of Brazil.

The molecular genetics of blood group polymorphism

Nearly 300 blood group specificities on red cells are known, many of which are polymorphic. The molecular mechanisms responsible for these polymorphisms are diverse, though the majority represent single nucleotide polymorphisms (SNPs) encoding amino acid substitutions. Other mechanisms include the following: gene deletion; single nucleotide deletion and sequence duplication, which introduce reading-frame shifts; nonsense mutation; intergenic recombination between closely-linked genes, giving rise to hybrid genes and hybrid proteins; and a SNP in the promoter region of a blood group gene. Examples of these genetic mechanisms are taken from the ABO, Rh, Kell, and Duffy blood group systems. Null phenotypes, in which no antigens of a blood group system are expressed, are not generally polymorphic, but provide good examples of the effect of inactivating mutations on blood group expression. As natural human ‘knock-outs’ they provide useful clues to the functions of blood group antigens. Knowledge of the molecular bases to blood group polymorphisms provides a means to predict blood group phenotype from genomic DNA with a high degree of accuracy. This currently has two main applications in transfusion medicine: for determining fetal blood groups to assess whether the fetus is at risk from haemolytic disease; and to determine blood group phenotypes in multiply transfused, transfusion-dependent patients, where serological tests are precluded by the presence of donor red cells. Other applications are being developed for the future.

The Basques: Review of Population Genetics and Mendelian Disorders

The Basques live at the western end of the Pyrenees along the Atlantic Ocean and are thought to represent the descendants of a pre-Neolithic people. They demonstrate marked specificities regarding language and genetics among the European populations. We review the published data on the population genetics and Mendelian disorders of the Basques. An atypical distribution in some blood group polymorphisms (ABO, Rhesus, and Duffy) was first found in this population. Subsequently, additional characteristics have been described with regard to proteins (enzymes and immunoglobulins) and the HLA system. The advent of molecular biology methods in the 1990s allowed further insights into Basque population genetics based mainly on Y-chromosome and mitochondrial DNA. In addition, the Basques demonstrate peculiarities regarding the distribution of various inherited diseases (i.e., unusual frequencies or founding effects). Taken together, these data support the idea of an ancient and still relatively unmixed population subjected to genetic drift.

몽고말의 적혈구항원형 및 혈액단백질형 분석

제주말의 혈통보존을 위한 기초자료를 마련할 목적으로 국내에서 사육중인 몽고말 19두를 대상으로 적혈구항원형 및 혈액단백질형의 표현형 분포와 유전자 빈도를 조사한 결과는 다음과 같다. 적혈구항원형의 표현형은 <TEX>$A^af$</TEX>(42.1%), <TEX>$C^a$</TEX>(89.5%), <TEX>$K^-$</TEX>((84.2%), <TEX>$U^a$</TEX>(63.2%), <TEX>$P^a$</TEX>(42.1%) <TEX>$P^-$</TEX>(42.1%), <TEX>$Q^c$</TEX>(31.6%), <TEX>$Q^-$</TEX>(31.6%)에서 높은 빈도를 나타냈으며 적혈구항원형 D 시스템의 유전자형은 <TEX>$D^cgm/dghm$</TEX> (15.8%), <TEX>$D^dghm/dghm$</TEX>(15.8%), <TEX>$D^ad/dghm$</TEX>(10.5%), <TEX>$D^ade/dghm$</TEX> (10.5%)가 높은 빈도 순으로 관찰되었다. 혈액단백질형 7개의 좌위에서는 <TEX>$AL^{AB}$</TEX>(52.6%), <TEX>$AIB^K$</TEX>( (89.5%), <TEX>$ES^I$</TEX>(63.2%), <TEX>$GC^F$</TEX>(78.9%), <TEX>$HB^{BI}$</TEX>(68.4%),<TEX>$PGD^F$</TEX>(84.2%), <TEX>$TF^{F1R}I$</TEX>(21.1%), <TEX>$TF^{F2R}I$</TEX>(21.1%)로 높은 빈도를 보였으며, <TEX>$HB^{A2B2}I$</TEX>(5.3%), <TEX>$PGD^{DS}I$</TEX>(5.3%)가 특이하게 관찰되었다. 적혈구항원형의 유전자 빈도를 조사한 결과 <TEX>$A^a$</TEX>(0.4211), <TEX>$C^a$</TEX>(0.8947), <TEX>$K^-$</TEX>(0.8421), <TEX>$U^a$</TEX>(0.6316), <TEX>$P^a$</TEX> (0.4474), <TEX>$Q^c$</TEX>(0.4474), <TEX>$D^{dghm}$</TEX>(0.4211)로 가장 높은 빈도를 보였으며, 혈액단백질형 7개 좌위에 대해서 유전자 빈도를 조사한 결과 <TEX>$AL^B$</TEX>(0.6579), <TEX>$AIB^K$</TEX>(0.9211), <TEX>$ES^I$</TEX>(0.7895), <TEX>$GC^F$</TEX>(0.8947), <TEX>$HB^BI$</TEX> (0.7895), <TEX>$PGD^F$</TEX>(0.8421), <TEX>$TF^R$</TEX>(0.3421)가 높은 빈도로 관찰되었다. The present study was carried out to investigate the blood markers of Mongolian horses. The blood redcell types and blood protein types(biochemical polymorphisrns) were tested from 19 Mongolian horses by serological and electrophoretic procedure, and their phenotypes and gene frequencies were estimated. The blood group and biochemical polymorphism phenotypes observed with high frequency were <TEX>$A^{af}$</TEX>(42.1%), <TEX>$C^a$</TEX>(89.5%), <TEX>$K^-$</TEX>(84.2%), <TEX>$U^a$</TEX>(63.2%), <TEX>$P^a$</TEX>(42.1%) <TEX>$P^-$</TEX>42.1%), <TEX>$Q^c$</TEX>(31.6%) <TEX>$Q^-$</TEX>(31.6%), <TEX>$AL^{AB}$</TEX>((52.6%), AI<TEX>$B^K$</TEX>(89.5%), <TEX>$ES^1$</TEX>(63.2%), <TEX>$GC^F$</TEX>(78.9%), <TEX>$HB^BI$</TEX>1(68.4%), PG<TEX>$D^F$</TEX>(84.2%), <TEX>$TF^{FIR}$</TEX>(21.1%), <TEX>$TF^{F2R}$</TEX>(21.1%)(21.1%), and genotypes <TEX>$D^{cgm/dghm}$</TEX>(15.8%), <TEX>$D^{dghm/dghm}$</TEX>(15.8%), <TEX>$D^{ad/dghm}$</TEX>(10.5%), <TEX>$D^{ade/dghm}$</TEX>(10.5%), in Mongolian horses, respectively. Alleles observed with high frequency were <TEX>$A^a$</TEX>(0.4211), <TEX>$C^a$</TEX>(0.8947), <TEX>$K^-$</TEX>(0.8421), <TEX>$U^a$</TEX>(0.6316), <TEX>$P^a$</TEX>(0.4474), <TEX>$Q^c$</TEX>(0.4474), <TEX>$D^{dghm}$</TEX>(0.4211), <TEX>$AL^B$</TEX>(0.6579), <TEX>$AIB^K$</TEX>(0.9211), <TEX>$ES^I$</TEX>(0.7895), <TEX>$GC^F$</TEX>(0.8947), <TEX>$HB^{BI}$</TEX>(0.7895), <TEX>$PGD^F$</TEX>(0.8421) and <TEX>$TF^R$</TEX>(0.3421) in Mongolian horses. These results present basic information for estimating the genetic relationships between the Korean native horse, and developing a system for parentage verification and individuals identification in Mongolian horse.

Editorial

The transfusion of red blood cells (RBCs) is now considered a well-settled and essential therapy. However, some difficulties and constraints still occur, such as long-term blood product shortage, blood donor population aging, known and yet unknown transfusion-transmitted infectious agents, growing cost of the transfusion supply chain management, and the inescapable blood group polymorphism barrier. Red blood cells can be now cultured in vitro from human hematopoietic, human embryonic, or human-induced pluripotent stem cells (hiPSCs). The highly promising hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the revolutionary development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here some futuristic but realistic scenarios regarding potential applications for alloimmunized patients and those with a rare blood group. We retrospectively studied a cohort of 16,486 consecutive alloimmunized patients (10-year period), showing 1 to 7 alloantibodies with 361 different antibody combinations. We showed that only 3 hiPSC clones would be sufficient to match more than 99% of the 16,486 patients in need of RBC transfusions. The study of the French National Registry of People with a Rare Blood Phenotype/Genotype (10-year period) shows that 15 hiPSC clones would cover 100% of the needs in patients of white ancestry. In addition, one single hiPSC clone would meet 73% of the needs in alloimmunized patients with sickle cell disease for whom rare cryopreserved RBC units were required. As a result, we consider that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloimmunization prevention in multiply transfused patients.