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Transfusion. 2009 Jun;49(6):1059-69. doi: 10.1111/j.1537-2995.2009.02102.x. Epub 2009 Feb 25.

D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters.

Author information

1
Institute for Transfusion Medicine, University Hospital, Ulm, Germany. willy.flegel@uni-ulm.de

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.

[Indexed for MEDLINE]

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