Huang C H, Reid M E, Chen Y
Lindsley F. Kimball Research Institute, New York Blood Center, NY 10021, USA.
Blood. 1995 Jul 15;86(2):784-90.
The D--phenotype of the human erythrocyte is a genetic variant of the Rh blood group system associated with the expression of D but not C, c, E, and e (designated non-D) antigens. In this report, we characterize the structure and expression of Rh polypeptide genes in two D--homozygotes of Italian origin. Southern blot analysis detected a gross deletion in their genomic DNA that correlated with the alteration of CcEe rather than the D polypeptide gene. With detailed exon mapping, the deletion was found to be partial and internal, encompassing exons 2 through 8 of the non-D gene. Analysis of Rh cDNAs showed that no functional mRNA was produced from the truncated non-D gene, whereas the D gene gave rise to one major and two minor mature transcripts. The full-length RhD cDNA sequence contained four nucleotide changes resulting in four amino acid substitutions on the polypeptide backbone. The shortened RhD cDNAs occurred as alternatively spliced isoforms lacking sequences corresponding to exons 7 and/or 8. The identification of a partial and internal deletion in the non-D gene shows that the molecular basis for the D--phenotype is heterogenous and that its alterations have occurred on different genetic backgrounds.
人类红细胞的D--表型是Rh血型系统的一种遗传变异，与D抗原的表达相关，但不表达C、c、E和e（称为非D）抗原。在本报告中，我们对两名意大利裔D--纯合子中Rh多肽基因的结构和表达进行了表征。Southern印迹分析在其基因组DNA中检测到一个大片段缺失，该缺失与CcEe而非D多肽基因的改变相关。通过详细的外显子定位，发现该缺失是部分性的且位于内部，涵盖非D基因的外显子2至8。对Rh cDNA的分析表明，截短的非D基因未产生功能性mRNA，而D基因产生了一种主要的和两种次要的成熟转录本。全长RhD cDNA序列包含四个核苷酸变化，导致多肽主链上有四个氨基酸替换。缩短的RhD cDNA以缺少对应于外显子7和/或8序列的可变剪接异构体形式出现。非D基因中部分性和内部缺失的鉴定表明，D--表型的分子基础是异质性的，并且其改变发生在不同的遗传背景上。
