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Marion E. Reid - One of the best experts on this subject based on the ideXlab platform.
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the jr Blood Group System isbt 032 molecular characterization of three new null alleles
Transfusion, 2013Co-Authors: Kim Hueroye, Gail Coghlan, Teresa Zelinski, Christine Lomasfrancis, Marion E. ReidAbstract:Background Jr(a) (ISBT 901005) is a high-prevalence antigen unassigned to a Blood Group System. People lacking this antigen have been found in all populations studied but most commonly in Asians. Two recent reports established that ABCG2-null alleles encode the Jr(a-) phenotype and these studies provided the impetus to study other Jr(a-) individuals. Study design and methods Blood samples were part of our rare donor-patient collection. DNA was isolated and analyzed by standard techniques. Results In samples from 13 Jr(a-) study subjects, we found six alleles with nonsense nucleotide changes, three (c.784T, c.1591T, and c.337T) were novel. Twelve of the samples were homozygous for nonsense single-nucleotide polymorphisms (SNPs): eight were c.376T, two were c.706T, one was c.784T, and one was c.1591T. Each of these alleles predicts a truncated ABCG2 product, Gln126Stop, Arg236Stop, Gly262Stop, and Gln531Stop, respectively. One study subject was heterozygous for two nonsense SNPs: c.337C/T (Arg113Stop) and c.736C/T (Arg246Stop). Conclusions Jr(a) is the sole antigen in the newly established JR Blood Group System (ISBT 032001). The previous ISBT designation (901005) is now obsolete. Since ABCG2null alleles define the Jr(a-) phenotype, an explanation for why no antithetical low-prevalence antigen to Jr(a) has been found, and also why anti-Jr(a) made by people with any of these JRnull alleles are mutually compatible has been determined. Based on our findings DNA-based genotyping can be developed to replace the serologic methods that are currently used to identify Jr(a-) Blood donors.
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molecular basis of the rare gene complex d c which encodes four low prevalence antigens in the rh Blood Group System
Blood, 2010Co-Authors: Christine Halter Hipsky, Kim Hueroye, Chenghan Huang, Christine Lomasfrancis, Marion E. ReidAbstract:Abstract 1117 Background: Over 40 years ago, the investigation of a case of fatal HDN in the third child of Madame Nou, a native of Ivory Coast, revealed that Madame Nou9s RBCs had an unusual phenotype in the Rh Blood Group System denoted DIVa(C)-/DIVa(C)-. Initially, her RBCs were shown to express a partial D, a weak form of C, and Goa (RH30) [Salmon, et al., Rev Franc Transf 1969;12:239]. Later her RBCs were shown to also express RH33, Riv (RH45), and FPTT (RH50) [Bizot, et al., Transfusion 1988;28:342; Delehanty, et al., Transfusion 1983;23:410, abstract]. R0Har and CeVA phenotypes are encoded by hybrid RHCE-D(5)-CE alleles (respectively, c+ and C+) and the RBCs express RH33 and FPTT antigens but not Goa or Riv [Noizat-Pirenne, et al. Transfusion 2002;42:627]. RHD*DIVa.2 encodes a partial D and the Goa antigen and frequently travels with RHCE*ce(1025T) (RHCE*ceTI) (Vege, et al., Transfusion 2007;47:159A). The purpose of this study was to determine the molecular basis associated with the rare DIVa(C)- complex. Material and Methods: Blood samples were obtained from three donors previously identified as having the DIVa(C)- haplotype. Molecular analyses were performed by standard methods and included AS-PCR, PCR-RFLP, genomic sequencing of specific exons, and cloning and direct sequencing of cDNA. Results: At the RHD locus all donors were heterozygous for RHD and RHD*DIVa.2 and at the RHCE locus all had a compound hybrid allele, which contains exons 2 and 3 from RHD*DIVa.2 (based on RHD*186G/T, RHD*410C/T, RHD*455A/C), and exon 5 from RHD. The altered RHCE is presumed to be in cis to RHD*DIVa.2. In all three probands RHCE*48 in exon 1 is G/C; presumably the G belonging to the in trans RHCE and the nt48C to the hybrid allele, and this assumption favors exon 1 of the hybrid being from RHCE. Thus, the RHCE allele is likely RHCE*CE-DIVa.2(2,3)-CE-D(5)-CE. The in trans allele in Proband 1 is RH*cE, in Proband 2 it is RHCE*ce 254C, 733G, and in Proband 3 it is RHCE*ce. Conclusions: The compound hybrid provides an explanation for the expression of the four low prevalence antigens on RBCs with the DIVa(C)- phenotype. RHD*DIVa.2 encodes the Goa antigen. The flanking of RHD exon 5 by RHCE exons in the compound hybrid likely results in RH33 and FPTT antigen expression because R0Har and CeVA RBCs express these two antigens. It is possible that the junction of RHD exon 3 to RHCE exon 4 is involved in the expression of Riv. The weak C expression could be a consequence of exons 2 and 3 from RHD*DIVa.2 in the compound hybrid because exon 2 of the wild type RHD is identical in sequence to exon 2 of RHCE*C. The three probands in our study had RHCE nt1025C/C (wild type) and thus, are not RHCE*ce(1025T). This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. Such a hybrid is not unprecedented in that RHD*DIIIa is involved in the RHD*DIIIa-CE(4-7)-D hybrid [(C)ceS type 1 in the r’S haplotype] As only one example of anti-Riv has been described, our findings provide a tool by which to predict the expression of Riv. Disclosures: No relevant conflicts of interest to declare.
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absence of domr a new antigen in the dombrock Blood Group System that weakens expression of dob gya hy joa and doya antigens
Transfusion, 2010Co-Authors: Flavia Pinheiro S Costa, Kim Hueroye, Christine Lomasfrancis, Laima Sausais, Randall W Velliquette, Eliete Da Costa Ferreira, Marion E. ReidAbstract:BACKGROUND: The Dombrock (Do) Blood Group System consists of six distinct antigens: Do a , Do b , Gy a , Hy, Jo a , and DOYA. Our finding of a pregnant patient whose red Blood cells (RBCs) were Hy+ but whose serum contained an apparent alloanti-Hy suggested the presence of a seventh antigen and prompted this study. STUDY DESIGN AND METHODS: Standard hemagglutination and polymerase chain reaction―based methods were used throughout. RESULTS: The patient's RBCs typed as Do(a-b+ W ), Gy(a+ w ), Hy+ w , Jo(a+ w ), and DOYA+ w . Her serum agglutinated RBCs with common Dombrock phenotypes. Hy― RBC samples were very weakly reactive or nonreactive, Jo(a―) and DOYA― RBC samples were reactive, and Gy(a―) RBC samples were nonreactive. Reactivity was obtained with RBCs treated with papain or α-chymotrypsin, but not with RBCs treated with trypsin or dithiothreitol. DNA analysis showed the patient to be DO * 793G (DO * B/DO * B), DO * 323G, DO * 350C, DO * 547T, and DO * 898G and revealed two homozygous nucleotide changes of DO * 431C>A and DO * 432C>A in Exon 2, which predicts a change of Ala (GCC) at Amino Acid 144 to Glu (GAA). This indicates that she is homozygous DO * B-WL with Nucleotide 431 and 432 changes, which without knowing the effect of the two novel changes, is predicted to encode the Do(a―b+), Gy(a+), Hy+, Jo(a+), DOYA+ phenotype. CONCLUSIONS: The antibody in the patient's plasma recognizes the high-prevalence antigen absent from her RBCs. The Ala144Glu change caused an absence of a high-prevalence Do antigen that we have named DOMR [provisional ISBT number 014007 (DO7)]. The absence of DOMR is associated with weakening of Do b , Gya, Hy, Jo a , and DOYA antigens.
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the fya fy6 and fy3 epitopes of the duffy Blood Group System recognized by new monoclonal antibodies identification of a linear fy3 epitope
British Journal of Haematology, 2004Co-Authors: Kazimiera Wasniowska, Elwira Lisowska, Gregory R Halverson, Asok Chaudhuri, Marion E. ReidAbstract:Summary Four new anti-Duffy murine monoclonal antibodies (MAbs): two anti-Fy6 (MIMA-107 and MIMA-108), one anti-Fya (MIMA-19) and one anti-Fy3 (MIMA-29) were characterized. Identification of epitopes by means of synthetic peptides (Pepscan) showed that the anti-Fy6 reacted most strongly with peptides containing the sequence 19QLDFEDV25 of the Duffy glycoprotein, and less strongly with peptides containing LDFEDV (MIMA-107) or LDF only (MIMA-108). The anti-Fya recognized epitope 38DGDYGA43 containing the Gly42 residue, which defines the Fya Blood Group antigen. MIMA-29 is the first anti-Fy3 reactive with a linear epitope 281ALDLL285 located in the fourth extracellular domain (ECD4, loop 3) of the Duffy glycoprotein. The four new antibodies extend the list of six anti-Fy MAbs formerly characterized by Pepscan analysis that allow some general conclusions. Fine specificities of various anti-Fya, or anti-Fy6 are not identical, but all of them recognize linear epitopes located around, respectively, Gly42 or between two potential N-glycosylation sites at Asn16 and Asn27. Anti-Fy3 recognize either a linear epitope located in ECD4, or a conformational epitope that includes amino acid residues of ECD4 and of other ECDs.
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dak a new low incidence antigen in the rh Blood Group System
Transfusion, 2003Co-Authors: Marion E. Reid, Kim Hueroye, Jill R Storry, Laima Sausais, E Tossas, Maria Rios, Elizabeth S Gloster, Scott T Miller, Carl Wolf, Christine LomasfrancisAbstract:BACKGROUND: Some low-incidence antigens in the Rh Blood Group System (e.g., VS, Rh32, FPTT) are expressed by more than one Rh complex. We describe a new low-incidence antigen that is present on RBCs with the partial D phenotypes, DIIIa or DOL, on RN RBCs and on one example of STEM+S RBCs. STUDY DESIGN AND METHODS: Standard hemagglutination testing was performed with two sera that agglutinated DIIIa RBCs on our in-house antibody identification panel. DNA-based assays were performed on selected samples. RESULTS: RBCs with the DIIIa (n = 31), DOL (n = 5), or RN (n = 10) phenotype were agglutinated by both sera, as were RBCs from one STEM+S person. Reactivity with RBCs of either DIIIa or DOL phenotypes was stronger than with RN RBCs and could not be separated by adsorption and elution. CONCLUSION: An antibody, anti-DAK, which recognizes a novel low-incidence antigen that is more strongly expressed on DIIIa and DOL RBCs than on RN RBCs is described. The antibody agglutinated RBCs from 4 percent of D+ African American Blood donors in New York. The antigen, DAK, has been assigned the ISBT number RH54 (004.054). (Less)
Fumiichiro Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Amino acid substitutions at sugar-recognizing codons confer ABO Blood Group System-related α1,3 Gal(NAc) transferases with differential enzymatic activity
Nature Publishing Group, 2019Co-Authors: Emili Cid, Miyako Yamamoto, Fumiichiro YamamotoAbstract:Abstract Functional paralogous ABO, GBGT1, A3GALT2, and GGTA1 genes encode Blood Group A and B transferases (AT and BT), Forssman glycolipid synthase (FS), isoglobotriaosylceramide synthase (iGb3S), and α1,3-galactosyltransferase (GT), respectively. These glycosyltransferases transfer N-acetyl-d-galactosamine (GalNAc) or d-galactose forming an α1,3-glycosidic linkage. However, their acceptor substrates are diverse. Previously, we demonstrated that the amino acids at codons 266 and 268 of human AT/BT are crucial to their distinct sugar specificities, elucidating the molecular genetic basis of the ABO glycosylation polymorphism of clinical importance in transfusion and transplantation medicine. We also prepared in vitro mutagenized ATs/BTs having any of 20 possible amino acids at those codons, and showed that those codons determine the transferase activity and sugar specificity. We have expanded structural analysis to include evolutionarily related α1,3-Gal(NAc) transferases. Eukaryotic expression constructs were prepared of AT, FS, iGb3S, and GT, possessing selected tripeptides of AT-specific AlaGlyGly or LeuGlyGly, BT-specific MetGlyAla, FS-specific GlyGlyAla, or iGb3S and GT-specific HisAlaAla, at the codons corresponding to 266–268 of human AT/BT. DNA transfection was performed using appropriate recipient cells existing and newly created, and the appearance of cell surface oligosaccharide antigens was immunologically examined. The results have shown that several tripeptides other than the originals also bestowed transferase activity. However, the repertoire of functional amino acids varied among those transferases, suggesting that structures around those codons differentially affected the interactions between donor nucleotide-sugar and acceptor substrates. It was concluded that different tripeptide sequences at the substrate-binding pocket have contributed to the generation of α1,3-Gal(NAc) transferases with diversified specificities
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molecular genetic analysis of the abo Blood Group System 4 another type of o allele
Vox Sanguinis, 1993Co-Authors: Fumiichiro Yamamoto, Miyako Yamamoto, Patricia D Mcneill, Senitiroh Hakomori, Imelda M Bromilow, Jennifer K M DuguidAbstract:We have encountered an allele which seems to be another type of O allele at the human histo-Blood Group ABO locus. We have determined the nucleotide sequence of this allele over the coding region in the last two coding exons. This allele does not possess the single-nucleotide deletion found common among all the O alleles previously analyzed. Compared with A1 allele, this allele has three nucleotide substitutions resulting in two amino acid substitutions. The introduction of these amino acid substitutions into the A1 transferase expression construct apparently abolished the enzymatic activity of A1 transferase.
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molecular genetic analysis of the abo Blood Group System 3 a x and b a alleles
Vox Sanguinis, 1993Co-Authors: Fumiichiro Yamamoto, Miyako Yamamoto, Patricia D Mcneill, Senitiroh Hakomori, Teresa HarrisAbstract:We have employed a PCR approach to determine the nucleotide sequences of the coding region in the last two coding exons of the histo-Blood Group ABO genes from one A(X) and one B(A) individual. Compared with A1 alleles, the (A(X)) allele has a single nucleotide substitution (T-->A at nucleotide 646) resulting in an amino acid substitution (phenylalanine-->isoleucine at amino acid 216). Compared with B alleles, the B(A) allele has two nucleotide substitutions (T-->C at nt. 657 and A-->G at nt. 703) resulting in an amino acid substitution (serine-->glycine at aa. 235). The amino acid substitution resulting from this B(A) allele is located at the second of the four amino acid substitutions which discriminate human A and B transferases, and the amino acid residue (glycine) is identical to that of A transferase suggesting the involvement of this amino acid or its surrounding area for the recognition and/or binding of the donor nucleotide sugars.
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molecular genetic analysis of the abo Blood Group System 2 cis ab alleles
Vox Sanguinis, 1993Co-Authors: Fumiichiro Yamamoto, Miyako Yamamoto, Patricia D Mcneill, Yoshihiko Kominato, Senitiroh Hakomori, Seiji Ishimoto, Sachiyo Nishida, Masayuki Shima, Yoshihiro FujimuraAbstract:We have determined the nucleotide sequence of the coding region in the last two coding exons of ABO genes from two cis-AB individuals (genotype cis-AB/O) with no consanguinity. In this region, cis-AB alleles from these 2 individuals were identical to one another while different from the A1 allele by two nucleotide substitutions. Both of these nucleotide substitutions result in amino acid substitutions. The first substitution is identical to the one previously found in the A2 allele. The other substitution is found at the fourth position of the four amino acid substitutions which discriminate A1 and B transferases.
Christine Lomasfrancis - One of the best experts on this subject based on the ideXlab platform.
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expansion of the kell Blood Group System two new high prevalence antigens and two novel k0 kellnull phenotypes
Transfusion, 2013Co-Authors: Christine Lomasfrancis, Makoto Uchikawa, Randall W Velliquette, Sunitha Vege, Akiko Fuchisawa, Yoshihiko Tani, Hiroko Moro, Asim K Debnath, Connie M WesthoffAbstract:Background The number of KEL alleles associated with new antigens or loss of expression of high-prevalence antigens continues to increase. We investigated KEL in five samples: two with K0 (null) phenotypes and three with normal Kell expression and antibodies to high-prevalence antigens. Study Design and Methods Red Blood cell (RBC) typing and antibody identification were by standard methods. Genomic DNA was isolated from white Blood cells and DNA array testing and sequencing of KEL exons was performed by standard methods. Results Proband 1, an Asian woman with Kp(b+) RBCs, presented with alloanti-Kpb. Four years later, the antibody was reactive with all RBCs except K0. She was homozygous for KEL c.877C>T change (p.Arg293Trp), and the high-prevalence antigen absent from her RBCs was named KHUL. Probands 2 and 3, both Japanese and homozygous for KEL c.875G>A (p.Arg292Gln), presented with an antibody reactive with all except K0 RBCs. The antibody, named KYOR, recognizes an antigen antithetical to KYO (KEL31). Proband 4, a pregnant Middle Eastern woman, presented with alloanti-Kpb, but her RBCs did not express Kell antigens. She was homozygous for KEL c.230G>T (p.Cys77Phe). Proband 5, a multiply transfused Caucasian female with an antibody reactive with all RBCs except K0 and lacking Kell antigens, was a compound heterozygote carrying a silenced allele c.574C>T (p.Arg192Stop) in trans to c.1664G>A (p.Gly555Glu). Conclusion We describe two new high-prevalence Kell antigens, KHUL (ISBT 006037; KEL37) and KYOR (ISBT 006038; KEL38), and two novel alleles encoding K0 phenotypes. We caution that antibodies produced by individuals with K0 RBCs or lacking high-prevalence antigens can present as anti-Kpb.
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the jr Blood Group System isbt 032 molecular characterization of three new null alleles
Transfusion, 2013Co-Authors: Kim Hueroye, Gail Coghlan, Teresa Zelinski, Christine Lomasfrancis, Marion E. ReidAbstract:Background Jr(a) (ISBT 901005) is a high-prevalence antigen unassigned to a Blood Group System. People lacking this antigen have been found in all populations studied but most commonly in Asians. Two recent reports established that ABCG2-null alleles encode the Jr(a-) phenotype and these studies provided the impetus to study other Jr(a-) individuals. Study design and methods Blood samples were part of our rare donor-patient collection. DNA was isolated and analyzed by standard techniques. Results In samples from 13 Jr(a-) study subjects, we found six alleles with nonsense nucleotide changes, three (c.784T, c.1591T, and c.337T) were novel. Twelve of the samples were homozygous for nonsense single-nucleotide polymorphisms (SNPs): eight were c.376T, two were c.706T, one was c.784T, and one was c.1591T. Each of these alleles predicts a truncated ABCG2 product, Gln126Stop, Arg236Stop, Gly262Stop, and Gln531Stop, respectively. One study subject was heterozygous for two nonsense SNPs: c.337C/T (Arg113Stop) and c.736C/T (Arg246Stop). Conclusions Jr(a) is the sole antigen in the newly established JR Blood Group System (ISBT 032001). The previous ISBT designation (901005) is now obsolete. Since ABCG2null alleles define the Jr(a-) phenotype, an explanation for why no antithetical low-prevalence antigen to Jr(a) has been found, and also why anti-Jr(a) made by people with any of these JRnull alleles are mutually compatible has been determined. Based on our findings DNA-based genotyping can be developed to replace the serologic methods that are currently used to identify Jr(a-) Blood donors.
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molecular basis of the rare gene complex diva c which encodes four low prevalence antigens in the rh Blood Group System
Vox Sanguinis, 2012Co-Authors: Christine Halter Hipsky, Chenghan Huang, Kim Hueroye, Christine Lomasfrancis, M E ReidAbstract:Background Over 40 years ago, an unusual Rh phenotype denoted DIVa(C)- was identified in a case of fatal haemolytic disease of the newborn in the third child of Madame Nou. Her RBCs expressed a partial D, weak C and four low-prevalence Rh antigens: Goa (RH30), Rh33 (RH33), Riv (RH45) and FPTT (RH50). The purpose of this study was to determine the molecular basis associated with this rare DIVa(C)- complex. Material and Methods Blood samples were from three donors previously identified as carrying the DIVa(C)- haplotype. Molecular analyses were performed by standard methods. Results The three donors were heterozygous for RHD and RHD*DIVa.2, and all carried a compound hybrid allele at the RHCE locus. This hybrid RHCE allele contained exons 2 and 3 from RHD*DIVa.2 and exon 5 from RHD [RHCE*CE-DIVa.2(2-3)-CE-D(5)-CE] and is in cis to RHD*DIVa.2. The RHCE allele on the in trans chromosome differs between the donors and is RHCE*cE in donor 1, RHCE*ce (254C, 733G) in donor 2 and RHCE*ce in donor 3. Conclusions The RHD*DIVa.2 encodes the Goa antigen, whereas the compound hybrid allele most likely encodes Rh33, Riv and FPTT. The weakly expressed C antigen on RBCs with the DIVa(C)- phenotype could be encoded by exons 2 and 3 from RHD*DIVa.2 in the compound hybrid. This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. As only one example of anti-Riv has been described, our molecular analysis and findings provide a tool by which to predict Riv expression.
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molecular basis of the rare gene complex d c which encodes four low prevalence antigens in the rh Blood Group System
Blood, 2010Co-Authors: Christine Halter Hipsky, Kim Hueroye, Chenghan Huang, Christine Lomasfrancis, Marion E. ReidAbstract:Abstract 1117 Background: Over 40 years ago, the investigation of a case of fatal HDN in the third child of Madame Nou, a native of Ivory Coast, revealed that Madame Nou9s RBCs had an unusual phenotype in the Rh Blood Group System denoted DIVa(C)-/DIVa(C)-. Initially, her RBCs were shown to express a partial D, a weak form of C, and Goa (RH30) [Salmon, et al., Rev Franc Transf 1969;12:239]. Later her RBCs were shown to also express RH33, Riv (RH45), and FPTT (RH50) [Bizot, et al., Transfusion 1988;28:342; Delehanty, et al., Transfusion 1983;23:410, abstract]. R0Har and CeVA phenotypes are encoded by hybrid RHCE-D(5)-CE alleles (respectively, c+ and C+) and the RBCs express RH33 and FPTT antigens but not Goa or Riv [Noizat-Pirenne, et al. Transfusion 2002;42:627]. RHD*DIVa.2 encodes a partial D and the Goa antigen and frequently travels with RHCE*ce(1025T) (RHCE*ceTI) (Vege, et al., Transfusion 2007;47:159A). The purpose of this study was to determine the molecular basis associated with the rare DIVa(C)- complex. Material and Methods: Blood samples were obtained from three donors previously identified as having the DIVa(C)- haplotype. Molecular analyses were performed by standard methods and included AS-PCR, PCR-RFLP, genomic sequencing of specific exons, and cloning and direct sequencing of cDNA. Results: At the RHD locus all donors were heterozygous for RHD and RHD*DIVa.2 and at the RHCE locus all had a compound hybrid allele, which contains exons 2 and 3 from RHD*DIVa.2 (based on RHD*186G/T, RHD*410C/T, RHD*455A/C), and exon 5 from RHD. The altered RHCE is presumed to be in cis to RHD*DIVa.2. In all three probands RHCE*48 in exon 1 is G/C; presumably the G belonging to the in trans RHCE and the nt48C to the hybrid allele, and this assumption favors exon 1 of the hybrid being from RHCE. Thus, the RHCE allele is likely RHCE*CE-DIVa.2(2,3)-CE-D(5)-CE. The in trans allele in Proband 1 is RH*cE, in Proband 2 it is RHCE*ce 254C, 733G, and in Proband 3 it is RHCE*ce. Conclusions: The compound hybrid provides an explanation for the expression of the four low prevalence antigens on RBCs with the DIVa(C)- phenotype. RHD*DIVa.2 encodes the Goa antigen. The flanking of RHD exon 5 by RHCE exons in the compound hybrid likely results in RH33 and FPTT antigen expression because R0Har and CeVA RBCs express these two antigens. It is possible that the junction of RHD exon 3 to RHCE exon 4 is involved in the expression of Riv. The weak C expression could be a consequence of exons 2 and 3 from RHD*DIVa.2 in the compound hybrid because exon 2 of the wild type RHD is identical in sequence to exon 2 of RHCE*C. The three probands in our study had RHCE nt1025C/C (wild type) and thus, are not RHCE*ce(1025T). This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. Such a hybrid is not unprecedented in that RHD*DIIIa is involved in the RHD*DIIIa-CE(4-7)-D hybrid [(C)ceS type 1 in the r’S haplotype] As only one example of anti-Riv has been described, our findings provide a tool by which to predict the expression of Riv. Disclosures: No relevant conflicts of interest to declare.
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absence of domr a new antigen in the dombrock Blood Group System that weakens expression of dob gya hy joa and doya antigens
Transfusion, 2010Co-Authors: Flavia Pinheiro S Costa, Kim Hueroye, Christine Lomasfrancis, Laima Sausais, Randall W Velliquette, Eliete Da Costa Ferreira, Marion E. ReidAbstract:BACKGROUND: The Dombrock (Do) Blood Group System consists of six distinct antigens: Do a , Do b , Gy a , Hy, Jo a , and DOYA. Our finding of a pregnant patient whose red Blood cells (RBCs) were Hy+ but whose serum contained an apparent alloanti-Hy suggested the presence of a seventh antigen and prompted this study. STUDY DESIGN AND METHODS: Standard hemagglutination and polymerase chain reaction―based methods were used throughout. RESULTS: The patient's RBCs typed as Do(a-b+ W ), Gy(a+ w ), Hy+ w , Jo(a+ w ), and DOYA+ w . Her serum agglutinated RBCs with common Dombrock phenotypes. Hy― RBC samples were very weakly reactive or nonreactive, Jo(a―) and DOYA― RBC samples were reactive, and Gy(a―) RBC samples were nonreactive. Reactivity was obtained with RBCs treated with papain or α-chymotrypsin, but not with RBCs treated with trypsin or dithiothreitol. DNA analysis showed the patient to be DO * 793G (DO * B/DO * B), DO * 323G, DO * 350C, DO * 547T, and DO * 898G and revealed two homozygous nucleotide changes of DO * 431C>A and DO * 432C>A in Exon 2, which predicts a change of Ala (GCC) at Amino Acid 144 to Glu (GAA). This indicates that she is homozygous DO * B-WL with Nucleotide 431 and 432 changes, which without knowing the effect of the two novel changes, is predicted to encode the Do(a―b+), Gy(a+), Hy+, Jo(a+), DOYA+ phenotype. CONCLUSIONS: The antibody in the patient's plasma recognizes the high-prevalence antigen absent from her RBCs. The Ala144Glu change caused an absence of a high-prevalence Do antigen that we have named DOMR [provisional ISBT number 014007 (DO7)]. The absence of DOMR is associated with weakening of Do b , Gya, Hy, Jo a , and DOYA antigens.
Connie M Westhoff - One of the best experts on this subject based on the ideXlab platform.
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expansion of the kell Blood Group System two new high prevalence antigens and two novel k0 kellnull phenotypes
Transfusion, 2013Co-Authors: Christine Lomasfrancis, Makoto Uchikawa, Randall W Velliquette, Sunitha Vege, Akiko Fuchisawa, Yoshihiko Tani, Hiroko Moro, Asim K Debnath, Connie M WesthoffAbstract:Background The number of KEL alleles associated with new antigens or loss of expression of high-prevalence antigens continues to increase. We investigated KEL in five samples: two with K0 (null) phenotypes and three with normal Kell expression and antibodies to high-prevalence antigens. Study Design and Methods Red Blood cell (RBC) typing and antibody identification were by standard methods. Genomic DNA was isolated from white Blood cells and DNA array testing and sequencing of KEL exons was performed by standard methods. Results Proband 1, an Asian woman with Kp(b+) RBCs, presented with alloanti-Kpb. Four years later, the antibody was reactive with all RBCs except K0. She was homozygous for KEL c.877C>T change (p.Arg293Trp), and the high-prevalence antigen absent from her RBCs was named KHUL. Probands 2 and 3, both Japanese and homozygous for KEL c.875G>A (p.Arg292Gln), presented with an antibody reactive with all except K0 RBCs. The antibody, named KYOR, recognizes an antigen antithetical to KYO (KEL31). Proband 4, a pregnant Middle Eastern woman, presented with alloanti-Kpb, but her RBCs did not express Kell antigens. She was homozygous for KEL c.230G>T (p.Cys77Phe). Proband 5, a multiply transfused Caucasian female with an antibody reactive with all RBCs except K0 and lacking Kell antigens, was a compound heterozygote carrying a silenced allele c.574C>T (p.Arg192Stop) in trans to c.1664G>A (p.Gly555Glu). Conclusion We describe two new high-prevalence Kell antigens, KHUL (ISBT 006037; KEL37) and KYOR (ISBT 006038; KEL38), and two novel alleles encoding K0 phenotypes. We caution that antibodies produced by individuals with K0 RBCs or lacking high-prevalence antigens can present as anti-Kpb.
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the rh Blood Group System in review a new face for the next decade
Transfusion, 2004Co-Authors: Connie M WesthoffAbstract:h is the most well-recognized Blood Group System after ABO, probably because of the dramatic presentation of a fetus suffering hemolytic disease of the newborn (HDN) following maternal alloimmunization to the D antigen. Even individuals not associated with medicine have heard of the “Rh factor” and are aware that it has some importance in pregnancy. The earliest recorded description of the syndrome dates to the 1600s from a French midwife who attended the delivery of a set of twins, one of which was hydropic and the other was jaundiced and died of kernicterus. The agent responsible for the wide range of fetal symptoms, from mild jaundice to fetal demise, remained obscure until 1941. Levine and colleagues observed that the delivery of a stillborn fetus and the adverse reaction in the mother to a Blood transfusion from the father were related and were the result of an immune reaction to a paternal antigen. Serologists’ relationship with the offending Blood Group System began when it was confused with a Rhesus monkey red Blood cell (RBC) protein, now termed LW, and much argument and debate ensued over who should receive credit for its discovery. Becoming aware of the antigen, however, was only the beginning of the story. This Blood Group System would become notorious for its complexity, with numerous antigens and multiple nomenclatures defining it. Several seminal events characterized the history of the Rh System. One of the most important was the observation that ABO mismatch between a mother and the fetus had a partial protective effect against immunization R to D. This suggested the rationale for the development of Rh immune globulin (RhIG). Although immunoglobulin M (IgM) antibodies did not provide protection, immunoglobulin G (IgG) anti-D was effective. By the early 1960s, a mere 20 years after the discovery of Rh incompatibility, an effective treatment was available. Despite their clinical importance, the extremely hydrophobic nature of the Rh proteins made biochemical studies difficult, and the proteins were not successfully isolated until the late 1980s. This led to the cloning of the genes in the 1990s and to major advances in our understanding of the Rh System. The molecular bases of most Rh antigens have been determined, and the RH gene structure explains why this System is so polymorphic. Specifically, the conventional Rh antigens are encoded by two genes, RHD and RHCE, but numerous gene conversion events between them create hybrid genes. The resulting novel hybrid proteins containing regions of RhD joined to RhCE, or the converse, generate the myriad of different Rh antigens. The goal of this review is to highlight the insights gained since the cloning of the genes, describe applications for RH molecular testing to clinical practice, introduce other members of the Rh family of proteins that are present in other tissues, and focus on the next piece of the Rh puzzle, that is, efforts to determine the structure and function of the Rh family of proteins.
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investigation of the human rh Blood Group System in nonhuman primates and other species with serologic and southern blot analysis
Journal of Molecular Evolution, 1994Co-Authors: Connie M Westhoff, Dwane E WylieAbstract:To investigate the evolution of the Rh Blood-Group System in anthropoid apes, New and Old World monkeys, and nonprimate animals, serologic typing of erythrocytes from these species with antibodies specific for the human Rh Blood-Group antigens was performed. In addition, genomic DNA from these animals was analyzed on Southern blots with a human Rh-specific cDNA.
Kim Hueroye - One of the best experts on this subject based on the ideXlab platform.
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the jr Blood Group System isbt 032 molecular characterization of three new null alleles
Transfusion, 2013Co-Authors: Kim Hueroye, Gail Coghlan, Teresa Zelinski, Christine Lomasfrancis, Marion E. ReidAbstract:Background Jr(a) (ISBT 901005) is a high-prevalence antigen unassigned to a Blood Group System. People lacking this antigen have been found in all populations studied but most commonly in Asians. Two recent reports established that ABCG2-null alleles encode the Jr(a-) phenotype and these studies provided the impetus to study other Jr(a-) individuals. Study design and methods Blood samples were part of our rare donor-patient collection. DNA was isolated and analyzed by standard techniques. Results In samples from 13 Jr(a-) study subjects, we found six alleles with nonsense nucleotide changes, three (c.784T, c.1591T, and c.337T) were novel. Twelve of the samples were homozygous for nonsense single-nucleotide polymorphisms (SNPs): eight were c.376T, two were c.706T, one was c.784T, and one was c.1591T. Each of these alleles predicts a truncated ABCG2 product, Gln126Stop, Arg236Stop, Gly262Stop, and Gln531Stop, respectively. One study subject was heterozygous for two nonsense SNPs: c.337C/T (Arg113Stop) and c.736C/T (Arg246Stop). Conclusions Jr(a) is the sole antigen in the newly established JR Blood Group System (ISBT 032001). The previous ISBT designation (901005) is now obsolete. Since ABCG2null alleles define the Jr(a-) phenotype, an explanation for why no antithetical low-prevalence antigen to Jr(a) has been found, and also why anti-Jr(a) made by people with any of these JRnull alleles are mutually compatible has been determined. Based on our findings DNA-based genotyping can be developed to replace the serologic methods that are currently used to identify Jr(a-) Blood donors.
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molecular basis of the rare gene complex diva c which encodes four low prevalence antigens in the rh Blood Group System
Vox Sanguinis, 2012Co-Authors: Christine Halter Hipsky, Chenghan Huang, Kim Hueroye, Christine Lomasfrancis, M E ReidAbstract:Background Over 40 years ago, an unusual Rh phenotype denoted DIVa(C)- was identified in a case of fatal haemolytic disease of the newborn in the third child of Madame Nou. Her RBCs expressed a partial D, weak C and four low-prevalence Rh antigens: Goa (RH30), Rh33 (RH33), Riv (RH45) and FPTT (RH50). The purpose of this study was to determine the molecular basis associated with this rare DIVa(C)- complex. Material and Methods Blood samples were from three donors previously identified as carrying the DIVa(C)- haplotype. Molecular analyses were performed by standard methods. Results The three donors were heterozygous for RHD and RHD*DIVa.2, and all carried a compound hybrid allele at the RHCE locus. This hybrid RHCE allele contained exons 2 and 3 from RHD*DIVa.2 and exon 5 from RHD [RHCE*CE-DIVa.2(2-3)-CE-D(5)-CE] and is in cis to RHD*DIVa.2. The RHCE allele on the in trans chromosome differs between the donors and is RHCE*cE in donor 1, RHCE*ce (254C, 733G) in donor 2 and RHCE*ce in donor 3. Conclusions The RHD*DIVa.2 encodes the Goa antigen, whereas the compound hybrid allele most likely encodes Rh33, Riv and FPTT. The weakly expressed C antigen on RBCs with the DIVa(C)- phenotype could be encoded by exons 2 and 3 from RHD*DIVa.2 in the compound hybrid. This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. As only one example of anti-Riv has been described, our molecular analysis and findings provide a tool by which to predict Riv expression.
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molecular basis of the rare gene complex d c which encodes four low prevalence antigens in the rh Blood Group System
Blood, 2010Co-Authors: Christine Halter Hipsky, Kim Hueroye, Chenghan Huang, Christine Lomasfrancis, Marion E. ReidAbstract:Abstract 1117 Background: Over 40 years ago, the investigation of a case of fatal HDN in the third child of Madame Nou, a native of Ivory Coast, revealed that Madame Nou9s RBCs had an unusual phenotype in the Rh Blood Group System denoted DIVa(C)-/DIVa(C)-. Initially, her RBCs were shown to express a partial D, a weak form of C, and Goa (RH30) [Salmon, et al., Rev Franc Transf 1969;12:239]. Later her RBCs were shown to also express RH33, Riv (RH45), and FPTT (RH50) [Bizot, et al., Transfusion 1988;28:342; Delehanty, et al., Transfusion 1983;23:410, abstract]. R0Har and CeVA phenotypes are encoded by hybrid RHCE-D(5)-CE alleles (respectively, c+ and C+) and the RBCs express RH33 and FPTT antigens but not Goa or Riv [Noizat-Pirenne, et al. Transfusion 2002;42:627]. RHD*DIVa.2 encodes a partial D and the Goa antigen and frequently travels with RHCE*ce(1025T) (RHCE*ceTI) (Vege, et al., Transfusion 2007;47:159A). The purpose of this study was to determine the molecular basis associated with the rare DIVa(C)- complex. Material and Methods: Blood samples were obtained from three donors previously identified as having the DIVa(C)- haplotype. Molecular analyses were performed by standard methods and included AS-PCR, PCR-RFLP, genomic sequencing of specific exons, and cloning and direct sequencing of cDNA. Results: At the RHD locus all donors were heterozygous for RHD and RHD*DIVa.2 and at the RHCE locus all had a compound hybrid allele, which contains exons 2 and 3 from RHD*DIVa.2 (based on RHD*186G/T, RHD*410C/T, RHD*455A/C), and exon 5 from RHD. The altered RHCE is presumed to be in cis to RHD*DIVa.2. In all three probands RHCE*48 in exon 1 is G/C; presumably the G belonging to the in trans RHCE and the nt48C to the hybrid allele, and this assumption favors exon 1 of the hybrid being from RHCE. Thus, the RHCE allele is likely RHCE*CE-DIVa.2(2,3)-CE-D(5)-CE. The in trans allele in Proband 1 is RH*cE, in Proband 2 it is RHCE*ce 254C, 733G, and in Proband 3 it is RHCE*ce. Conclusions: The compound hybrid provides an explanation for the expression of the four low prevalence antigens on RBCs with the DIVa(C)- phenotype. RHD*DIVa.2 encodes the Goa antigen. The flanking of RHD exon 5 by RHCE exons in the compound hybrid likely results in RH33 and FPTT antigen expression because R0Har and CeVA RBCs express these two antigens. It is possible that the junction of RHD exon 3 to RHCE exon 4 is involved in the expression of Riv. The weak C expression could be a consequence of exons 2 and 3 from RHD*DIVa.2 in the compound hybrid because exon 2 of the wild type RHD is identical in sequence to exon 2 of RHCE*C. The three probands in our study had RHCE nt1025C/C (wild type) and thus, are not RHCE*ce(1025T). This is the first report of RHD*DIVa.2 being involved in a hybrid gene at the RHCE locus. Such a hybrid is not unprecedented in that RHD*DIIIa is involved in the RHD*DIIIa-CE(4-7)-D hybrid [(C)ceS type 1 in the r’S haplotype] As only one example of anti-Riv has been described, our findings provide a tool by which to predict the expression of Riv. Disclosures: No relevant conflicts of interest to declare.
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absence of domr a new antigen in the dombrock Blood Group System that weakens expression of dob gya hy joa and doya antigens
Transfusion, 2010Co-Authors: Flavia Pinheiro S Costa, Kim Hueroye, Christine Lomasfrancis, Laima Sausais, Randall W Velliquette, Eliete Da Costa Ferreira, Marion E. ReidAbstract:BACKGROUND: The Dombrock (Do) Blood Group System consists of six distinct antigens: Do a , Do b , Gy a , Hy, Jo a , and DOYA. Our finding of a pregnant patient whose red Blood cells (RBCs) were Hy+ but whose serum contained an apparent alloanti-Hy suggested the presence of a seventh antigen and prompted this study. STUDY DESIGN AND METHODS: Standard hemagglutination and polymerase chain reaction―based methods were used throughout. RESULTS: The patient's RBCs typed as Do(a-b+ W ), Gy(a+ w ), Hy+ w , Jo(a+ w ), and DOYA+ w . Her serum agglutinated RBCs with common Dombrock phenotypes. Hy― RBC samples were very weakly reactive or nonreactive, Jo(a―) and DOYA― RBC samples were reactive, and Gy(a―) RBC samples were nonreactive. Reactivity was obtained with RBCs treated with papain or α-chymotrypsin, but not with RBCs treated with trypsin or dithiothreitol. DNA analysis showed the patient to be DO * 793G (DO * B/DO * B), DO * 323G, DO * 350C, DO * 547T, and DO * 898G and revealed two homozygous nucleotide changes of DO * 431C>A and DO * 432C>A in Exon 2, which predicts a change of Ala (GCC) at Amino Acid 144 to Glu (GAA). This indicates that she is homozygous DO * B-WL with Nucleotide 431 and 432 changes, which without knowing the effect of the two novel changes, is predicted to encode the Do(a―b+), Gy(a+), Hy+, Jo(a+), DOYA+ phenotype. CONCLUSIONS: The antibody in the patient's plasma recognizes the high-prevalence antigen absent from her RBCs. The Ala144Glu change caused an absence of a high-prevalence Do antigen that we have named DOMR [provisional ISBT number 014007 (DO7)]. The absence of DOMR is associated with weakening of Do b , Gya, Hy, Jo a , and DOYA antigens.
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new antigen in the dombrock Blood Group System doya ablates expression of doa and weakens expression of hy joa and gya antigens
Transfusion, 2010Co-Authors: Beate Mayer, Kim Hueroye, Christine Lomasfrancis, Dwane E Wylie, Nicole Thornton, Salih Yurek, Joyce Poole, Thilo Bartolmas, Abdulgabar Salama, Randall W VelliquetteAbstract:BACKGROUND: The Dombrock (Do) Blood Group System consists of five distinct antigens: Doa, Dob, Gya, Hy, and Joa. Our finding of a patient whose plasma contained a Do-related alloantibody suggested the presence of a sixth antigen. STUDY DESIGN AND METHODS: Standard hemagglutination, flow cytometry, and polymerase chain reaction (PCR)-based methods were used throughout. Protein homology modeling was used to map the amino acid change on the protein structure. RESULTS: The patient's red Blood cells (RBCs) typed as Do(a−b−), Hy+w, Jo(a+w), and Gy(a+w). The patient's plasma agglutinated RBCs with common Dombrock phenotypes. Reactivity with Hy– and Jo(a−) RBC samples was weak, and Gy(a−) RBC samples were nonreactive. DNA analysis showed the patient to be DO*793A (DO*A/DO*A), DO*323G, and DO*350C, which predicts the Do(a+b−), Hy+, and Jo(a+) phenotype, and revealed a homozygous single-nucleotide change of 547T>G in Exon 2 that is predicted to change tyrosine at Amino Acid Position 183 to aspartic acid. This missense substitution introduced a BtgZI restriction enzyme site. The sequence data were confirmed with a PCR–restriction fragment length polymorphism assay and revealed that the patient's parents and children were heterozygous DO*547T/G. Homology modeling predicted that the 183Tyr substitution by Asp altered the Cys182 environment and influenced the formation and/or stability of the Cys182-Cys231 disulfide bond. CONCLUSION: The patient's DO genes have a single-nucleotide change, which leads to the absence of the high-prevalence antigen DOYA. The absence of this antigen is associated with 183Asp and silencing of Doa and weakening of Gya, Hy, and Joa antigens.
