The study on the nucleotide sequences of the RH genes and the Rh genotyping.

Rh血型的分子分析结果如下：(1) RHD和RHCE基因的核苷酸序列基本确定。(2) RHD和RHCE基因间隔区的核苷酸测序基本完成。(3)在RHD基因和RHCE基因的内含子8上发现了简单序列重复多态性，这两个基因都含有5bp重复单元（AAAAT）n位点。该短串联重复序列（STR）的多态性表明，RHD阴性的无功能RHD基因可能是由DCe单倍型突变产生的，该突变消除了RHD基因。基于这些发现，STR多态性可能为RH单倍型的分子进化提供线索。(4)我们证明了杂种RHD- ce -D基因的基因组组织导致了D^<va>的表型，并表明D^<va>基因是由RHD和RHCE基因在相对较小的区域内的基因转换产生的。该研究还揭示了与D^<va>表型相关的新的部分D的存在，我们将其称为D^<va>样表型。(5)在Rhnull表型的拟子中，分子分析显示RHAG-cDNA缺失122bp，这是由于纯合剪接突变引起的。这一结果证实了RHAG基因最有可能是Rhnufl病例的调控基因。在骨髓增生异常综合征（MDS）患者中，根据MDS的进展，Rh系统的表型从D（+）、C（+）、C（+）、E（+）、E（+）转变为D（-）、C（-）、C（+）、E（-）、E（+）。其原因被证明是含有RHD和RHCE基因的微缺失。

The molecular analyses on the Rh blood group showed the following results.(1) The nucleotide sequences of RHD and RHCE genes were almost determined.(2) The nucleotide-sequencing of the spacer region between the RHD and RHCE genes was nearly finished.(3) We identified simple sequence repeat polymorphism in intron 8 of the RHD and RHCE genes, both of which contained the 5bp repeat unit, (AAAAT)n in loci. The polymorphisms of this short tandem repeat (STR) suggests that the RhD-negative with a non-functional RHD gene might have arisen from DCe haplotype via mutation, which abolished the RHD gene. Based on these findings, the STR polymorphisms may shed light upon the molecular evolution of RH haplotype.(4) We demonstrated a genomic organization of the hybrid RHD-CE-D gene leading to the D^<va> jthenotype, and showed that the D^<va> gene was generated from gene conversion between the RHD and RHCE genes in relatively small regions. This study also revealed that the presence of a new partial D associated with the D^<va> phenotype, which we termed the D^<va>-like phenotype.(5) In a propositus with the Rhnull phenotype, the molecular analyses showed a deletion of 122bp in the RHAG-cDNA, which was revealed to be due to a homozygous splicing mutation. This result confirms that the RHAG gene is the most likely candidate for the regulator gene of Rhnufl cases.In a patient with myelodysplastic syndrome (MDS), the phenotype of the Rh system altered from D(+), C(+), c(+), E(+), e(+) to D(-), C(-), c(+), E(-), e(+) according to the progression of MDS.Its reason was demonstrated to be microdeletion containing the RHD and RHCE genes.