权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Further investigation on the Rh blood group system for the expression of the RH gene and the epitopes of the Rh antigens

Rh血型系统RH基因表达及Rh抗原表位的进一步研究

基本信息

批准号：
13557038
负责人：
KAJII Eiji
金额：
$ 9.09万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557038/
关键词：
Rh blood group Rh variant Partial D Weak D Molecular genetics RHD gene RHCE gene Mouse genome Rh式血液型 Rh30遺伝子マウスオーソログ weak D エピトープ変異型 Rhmod 自己免疫性溶血性貧血

项目摘要

The mouse genomic sequence of the region containing the gene Rhced, the orthologue to the human gene RH30, was entirely determined and compared with the corresponding human genomic region. Two genes Smpl and AK003528 (an orthologue of FLJ10747), flank Rhced. Neither sequences homologous to the characteristic nucleotide elements flanking the RHD gene in human (rhesus boxes) nor an additional Rh gene were found within the mouse region sequenced. This result demonstrate that this chromosomal region of the mouse comprises five genes (FLJ10474-RHCE-SMP1-NPD014-P29) that exhibit syntenic homology with the corresponding human region, which suggests that the RHD gene and rhesus boxes were inserted later.The molecular characterization of weak D and partial D phenotypes was performed. The mutations - G212C (new weak D type), V270G (weak D type 1), and G358A (type 2) - in transmembranous regions had obvious effects on the D epitopes recognized by monoclonal anti-D antibodies. This result provide direct evidence that these mutations can account for weak D phenotypes. A novel partial D phenotype, termed DT1 was found. The DT1 phenotype affected the D polypeptide within the fourth external loop, resulting in a new RHD-CE (entire exon 5)-D hybrid gene. It is worth noting that P226, encoded by exon 5, is derived from E of RhCE in the DT1 polypeptide.The screening system for detecting the autoantigens in autoimmune hemolytic anemia (AIHA) was constructed by using several recombinant Rh antigens or band 3 protein-expressing KU812 cells. The autoantigens in twenty patients with AIHA were Rh-related ones in 15 cases and band 3 protein in 7 cases.

完全确定了含有基因Rhced（人基因RH 30的直向同源物）的区域的小鼠基因组序列，并与相应的人基因组区域进行了比较。两个基因Smpl和AK 003528（FLJ 10747的直向同源物），侧接Rhced。在测序的小鼠区域内，既没有发现与人类RHD基因侧翼的特征性核苷酸元件（恒河猴盒）同源的序列，也没有发现额外的Rh基因。结果表明，该小鼠染色体区域包含5个基因（FLJ 10474-RHCE-SMP 1-NPD 014-P29），它们与人相应区域具有同线同源性，提示RHD基因和rhesus boxes是后来插入的。跨膜区的G212 C（新弱D型）、V270 G（弱D 1型）和G358 A（弱D 2型）突变对抗D单克隆抗体识别的D表位有明显影响。这一结果提供了直接的证据，这些突变可以解释弱D表型。发现了一种新的部分D表型，命名为DT 1，DT 1表型影响了第四外环内的D多肽，产生了一个新的RHD-CE（整个外显子5）-D杂合基因。P226基因是由DT 1多肽中RhCE的E基因编码的，P226基因由外显子5编码。20例AIHA患者的自身抗原为Rh相关抗原15例，带3蛋白7例。