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Outliers in RhD membrane integration are explained by variant RH haplotypes
Author(s) -
Yu Xinjian,
Wagner Franz F.,
Witter Bernd,
Flegel Willy A.
Publication year - 2006
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2006.00902.x
Subject(s) - antigen , allele , haplotype , abo blood group system , rh blood group system , microbiology and biotechnology , gene , immunology , chemistry , biology , antibody , genetics
BACKGROUND: Variations in a multipass transmembrane protein may affect its membrane integration. To study this effect, the systematic molecular characterization of variant D antigen density is a suitable model. Unlike most other membrane proteins, the expression of the D antigen is often determined by a single allele, because it occurs frequently in hemizygous form. STUDY DESIGN AND METHODS: The D antigen density distribution of 530 CcDee, 475 ccDEe, and 514 ccDee random samples was established by flow cytometry. The molecular bases of samples with D antigen densities outside a bell‐shaped peak was investigated. RESULTS: The antigen densities of 499 CcDee, 437 ccDEe, and 480 ccDee samples formed bell‐shaped peaks. Three, 10, and 12 samples, respectively, had decreased antigen densities and carried variant RHD alleles. Weak D type 19, RHD (I204T); weak D type 20, RHD (F417S); and the partial D DYU (also known as DQC), RHD (R234W) were new RHD alleles. Twenty‐eight CcDee, 28 ccDEe, and 22 ccDee samples had increased antigen densities; 53 of them lacked a hybrid Rhesus box and were thus predicted to be RHD homozygous. Eight ccDee samples were predicted to be heterozygous despite a large relative dose of RHD to RHCE alleles in quantitative polymerase chain reaction. One of these samples was further investigated and carried an RHD‐CE hybrid transcript characteristic for a ‐D‐ haplotype. CONCLUSIONS: Unusual little and large RhD protein integration into the membrane could be traced to a host of distinct protein variants. Weak expression of D antigen was invariably associated with variant RHD alleles. Larger than normal D antigen density may often be caused by the presence of two D encoding alleles, which may be located in cis, and confounding zygosity testing that is solely based on gene copy number.