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| 2. |
- Lee, Yan Quan, et al.
(författare)
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A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xgnull phenotype, underlying anti-Xga production
- 2019
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 59:5, s. 1843-1849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .STUDY DESIGN AND METHODS: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.RESULTS: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence.CONCLUSION: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xgnull phenotype. This deletion was found in 10 of 11 anti-Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored.
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| 3. |
- Christophersen, Mikael K., et al.
(författare)
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SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.
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| 4. |
- Goel, Suchi, et al.
(författare)
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RIFINs are adhesins implicated in severe Plasmodium falciparum malaria
- 2015
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:4, s. 314-317
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Tidskriftsartikel (refereegranskat)abstract
- Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), bind to RBCs-preferentially of blood group A-to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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| 5. |
- Hellberg, Åsa, et al.
(författare)
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A novel RHCE*02 allele, containing the single-nucleotide change c.460A>G, encodes weakened expression of C and e antigens
- 2016
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 56:9, s. 2391-2392
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Tidskriftsartikel (refereegranskat)abstract
- We report a novel RHCE*02 allele in a Swedish blood donor that is characterized by the change c.460A>G (Arg154Gly). The blood donor's red blood cells showed variable reactivity with different monoclonal anti-C and anti-e and antigen strength was markedly weakened. We believe that these changes represent both a quantitative and qualitative alteration of the antigens encoded by this allele.
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| 6. |
- Jongruamklang, Philaiphon, et al.
(författare)
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Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of 36 blood group alleles among 396 Thai samples reveals region-specific variants
- 2018
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 58:7, s. 1752-1762
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Blood group phenotype variation has been attributed to potential resistance to pathogen invasion. Variation was mapped in blood donors from Lampang (northern region) and Saraburi (central region), Thailand, where malaria is endemic. The previously unknown blood group allele profiles were characterized and the data were correlated with phenotypes. The high incidence of the Vel-negative phenotype previously reported in Thais was investigated. STUDY DESIGN AND METHODS: DNA from 396 blood donors was analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Outliers were investigated by serology and DNA sequencing. Allele discrimination assays for SMIM1 rs1175550A/G and ACKR1 rs118062001C/T were performed and correlated with antigen expression. RESULTS: All samples were phenotyped for Rh, MNS, and K. Genotyping/phenotyping for RhD, K, and S/s showed 100% concordance. Investigation of three RHCE outliers revealed an e-variant antigen encoded by RHCE*02.22. Screening for rs147357308 (RHCE c.667T) revealed a frequency of 3.3%. MN typing discrepancies in 41 samples revealed glycophorin variants, of which 40 of 41 were due to Mia. Nine samples (2.3%) were heterozygous for FY*01W.01 (c.265C>T), and six samples (1.5%) were heterozygous for JK*02N.01. All samples were wildtype SMIM1 homozygotes with 97% homozygosity for rs1175550A. CONCLUSIONS: Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry is an efficient method for rapid routine genotyping and investigation of outliers identified novel variation among our samples. The expected high prevalence of the Mi(a+) phenotype was observed from both regions. Of potential clinical relevance in a region where transfusion-dependent thalassemia is common, we identified two RHCE*02 alleles known to encode an e-variant antigen.
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| 8. |
- Möller, Mattias, et al.
(författare)
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Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system
- 2018
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 132:3, s. 334-338
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Tidskriftsartikel (refereegranskat)abstract
- The Xga blood group is differentially expressed on erythrocytes from men and women. The underlying gene, PBDX, was identified in 1994, but the molecular background for Xga expression remains undefined. This gene, now designated XG, partly resides in pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xga allele frequencies in different populations with 2612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution. The same single-nucleotide polymorphism (SNP) had the most significant impact on XG transcript levels in whole blood (P 5 2.0 3 10222). The minor allele, rs311103C, disrupts a GATA-binding motif 3.7 kb upstream of the transcription start point. This silences erythroid XG messenger RNA expression and causes the Xg(a2) phenotype, a finding corroborated by SNP genotyping in 158 blood donors. Binding of GATA1 to biotinylated oligonucleotide probes with rs311103G but not rs311103C was observed by electrophoretic mobility shift assay and proven by mass spectrometry. Finally, a luciferase reporter assay indicated this GATA motif to be active for rs311103G but not rs311103C in HEL cells. By using an integrated bioinformatic and molecular biological approach, we elucidated the underlying genetic basis for the last unresolved blood group system and made Xga genotyping possible.
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| 9. |
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| 10. |
- Storry, Jill R., et al.
(författare)
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International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology : Report of the Dubai, Copenhagen and Toronto meetings
- 2019
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007. ; 114:1, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: The International Society of Blood Transfusion (ISBT) Working Party for Red Cell Immunogenetics and Blood Group Terminology meets in association with the ISBT congress and has met three times since the last report: at the international meetings held in Dubai, United Arab Emirates, September 2016 and Toronto, Canada, June 2018; and at a regional congress in Copenhagen, Denmark, June 2017 for an interim session. Methods: As in previous meetings, matters pertaining to blood group antigen nomenclature and classification were discussed. New blood group antigens were approved and named according to the serologic and molecular evidence presented. Results and conclusions: Fifteen new blood group antigens were added to eight blood group systems. One antigen was made obsolete based on additional data. Consequently, the current total of blood group antigens recognized by the ISBT is 360, of which 322 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known system. Clinically significant blood group antigens continue to be discovered, through serology/sequencing and/or recombinant or genomic technologies.
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