| 1. |
- Flegel, Willy A, et al.
(författare)
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D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters
- 2009
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 49:6, s. 1059-1069
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One branch of the RHD phylogenetic tree is represented by the weak D type 4 cluster of alleles with F223V as the primordial amino acid substitution. F223V as well as a large number of further substitutions causing D variants are located at the extracellular RhD protein vestibule, which represents the entrance to the transmembraneous channel of the RhD protein. STUDY DESIGN AND METHODS: RHD and RHCE nucleotide sequences were determined from genomic DNA and cDNA. D epitope patterns were established with commercial monoclonal anti-D panels. RESULTS: The RHD alleles DOL-1 and DOL-2 had the two amino acid substitutions M170T (509T>C) and F223V (667T>G) in common. DOL-2 harbored the additional substitution L378V (1132C>G). Both alleles were observed in Africans and are probably evolutionary related. DMI carried M170I (510G>A), which differed from the DOL-typical substitution. DFW and DFL harbored the substitutions H166P (497A>C) and Y165C (494A>G). The antigen densities of DOL-1, DFL, and DFW were only moderately reduced. CONCLUSION: DOL-1 and DOL-2 belong to the weak D type 4 cluster of RHD alleles. Together with DMI, DFL, and DFW they represent D variants with amino acid substitutions located at extracellular loops 3 or 4 lining the RhD protein vestibule. These substitutions were of minor influence on antigen density while adjacent substitutions in the transmembraneous section caused weak D antigen expression. All these D variants were partial D and alloanti-D immunizations have been observed in DOL-1, DMI, and DFL carriers. The substitution at position 170 causes partial D although located deep in the vestibule.
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| 2. |
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| 3. |
- Hellberg, Åsa, et al.
(författare)
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Molecular basis of the globoside-deficient P(k) blood group phenotype. Identification of four inactivating mutations in the UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase gene.
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:33, s. 29455-29459
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Tidskriftsartikel (refereegranskat)abstract
- The biochemistry and molecular genetics underlying the related carbohydrate blood group antigens P, P(k), and LKE in the GLOB collection and P1 in the P blood group system are complex and not fully understood. Individuals with the rare but clinically important erythrocyte phenotypes P(1)k and P(2)k lack the capability to synthesize P antigen identified as globoside, the cellular receptor for Parvo-B19 virus and some P-fimbriated Escherichia coli. As in the ABO system, naturally occurring antibodies, anti-P of the IgM and IgG class with hemolytic and cytotoxic capacity, are formed. To define the molecular basis of the P(k) phenotype we analyzed the full coding region of a candidate gene reported in 1998 as a member of the 3-beta-galactosyltransferase family but later shown to possess UDP-N-acetylgalactosamine:globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase or globoside synthase activity. Homozygosity for different nonsense mutations (C(202) --> T and 538insA) resulting in premature stop codons was found in blood samples from two individuals of the P(2)k phenotype. Two individuals with P(1)k and P(2)k phenotypes were homozygous for missense mutations causing amino acid substitutions (E266A or G271R) in a highly conserved region of the enzymatically active carboxyl-terminal domain in the transferase. We conclude that crucial mutations in the globoside synthase gene cause the P(k) phenotype.
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| 4. |
- Irshaid, Nidal M, et al.
(författare)
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Novel alleles at the JK blood group locus explain the absence of the erythrocyte urea transporter in European families.
- 2002
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 116:2, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- The Kidd (JK) blood group system is of importance in transfusion medicine. The Jk(null) phenotype is associated with absence of the urea transporter in erythrocytes and moderately reduced ability to concentrate urine. We and others recently reported different molecular alterations in the silenced Jkb-like alleles of Polynesians and Finns, populations with higher Jk(null) frequencies. Here we report novel molecular bases of this phenotype in Caucasians. Blood samples from a Swiss and an English family were investigated by serological methods, urea haemolysis test and JK genotyping. Genomic DNA and JK mRNA were sequenced. Genotyping showed homozygosity for Jka-like alleles. The Swiss Jk(null) alleles deviated from wild-type Jka sequence by a nonsense mutation in exon 7 causing an immediate stop codon (Tyr194stop). The English Jk(null) alleles revealed a genomic 1.6 kilobase pair deletion including exons 4 and 5, the former of which includes the translation start codon. Multiple mRNA splicing variants were detected in reticulocytes but exons 3-5 were absent in all transcripts analysed. Screening for these alleles was negative in random donors. Two novel molecular alterations at the JK locus were defined and a multiplex polymerase chain reaction method for detection of the five known silent Jk alleles was developed to complement JK genotyping in clinical transfusion medicine.
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| 5. |
- Sjöberg Wester, Elisabet, et al.
(författare)
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Genetic basis of the K phenotype in the Swedish population.
- 2005
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 45:4, s. 545-549
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in Undetermined BACKGROUND: The absence of all Kell blood group antigens (K0 phenotype) is very rare. K0 persons, however, can produce clinically significant anti-Ku (K5) after transfusion and/or pregnancy and require K0 blood for transfusion. Ten alleles giving rise to the K0 phenotype have been reported: different populations were studied although none from Scandinavia. STUDY DESIGN AND METHODS: Three K0 samples were identified by blood banks in Sweden (Uppsala,Umeå, and Linköping) during a 20-year period. Kell antigen typing was performed with standard serologic techniques by the respective blood banks and K 0 status was confirmed by the International Blood GroupReference Laboratory in Bristol, England. Polymerase chain reaction and DNA sequencing of the KEL coding region (exons 1-19) was performed on genomic DNA. RESULTS:The Uppsala K0 was homozygous for a 1540C>T substitution in exon 13, leading to an immediate stop codon. The Umeå K0 was homozygous for 1023delG in exon 8 that results in a frameshift and a premature stop codon in exon 9. In the Linköping K0, a previously reported mutation g>a at +1 of intron 3 was found. CONCLUSION: Two novel and one previously reported null alleles at the KEL locus are described. The identified nonsense mutations abolish expression of the Kell glycoprotein and are thus responsible for the K0 phenotype in these Swedish families.
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