Abstract:
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.
journal_name
Transfusionjournal_title
Transfusionauthors
Yu X,Wagner FF,Witter B,Flegel WAdoi
10.1111/j.1537-2995.2006.00902.xsubject
Has Abstractpub_date
2006-08-01 00:00:00pages
1343-51issue
8eissn
0041-1132issn
1537-2995pii
TRF00902journal_volume
46pub_type
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