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Gene Review

RHD  -  Rh blood group, D antigen

Homo sapiens

Synonyms: Blood group Rh(D) polypeptide, CD240D, DIIIc, RH, RH30, ...
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Disease relevance of RHD


High impact information on RHD

  • It suggested that there is some relationship between the RHD gene and the RhC phenotypes in RhD-negative individuals [6].
  • Additionally, the RHD gene detected in the RhD-negative donors seemed to be intact through sequencing of the RhD polypeptide cDNA and the promoter region of RHD gene [6].
  • Recent molecular studies on the Rh blood group system have shown that the Rh locus of each haploid RhD-positive chromosome is composed of two structural genes: RHD and RHCE, whereas the locus is made of a single gene (RHCE) on each haploid RhD-negative chromosome [6].
  • Prenatal detection of rhesus D genotype [7].
  • Peripheral-blood mononuclear cells from an individual known to produce antibody to the rhesus D blood group were enriched for specific antibody-producing cells before transformation with Epstein-Barr virus [8].

Chemical compound and disease context of RHD

  • Using radioligand binding, RT-PCR, and Southern blot analyses, we evaluated whether agonist [D-Trp6]LH-RH and antagonist Cetrorelix could affect the levels of receptors for LH-RH and EGF and expression of mRNA for these receptors in DU-145 human androgen-independent prostate cancers xenografted into nude mice [9].

Biological context of RHD


Anatomical context of RHD

  • We evaluated the clinical utility of this method to ascertain the RhD antigen in 10 patients with warm-type autoimmune haemolytic anaemia (AIHA) and 14 samples of amniotic fluids [15].
  • Red blood cells of weak D phenotype have a much reduced number of presumably complete D antigens that were repeatedly reported to carry the amino acid sequence of the regular RhD protein [16].
  • The PCR amplification of an RhPII-specific region from reticulocyte RNA and genomic DNA in all the family proved that the RhPII gene exists in both RhD-positive and RhD-negative individuals [17].
  • Subsequent chorionic villus sample analysis revealed that 2 of these 4 women with negative RHD and RASSF1A signals were in fact carrying RhD-positive fetuses [18].
  • Conventional methods for prenatal fetal RhD status determination involve invasive procedures such as fetal blood sampling and amniocentesis [19].

Associations of RHD with chemical compounds


Other interactions of RHD

  • The duplication event leading to RH50 and RH30 genes was estimated to have occurred between 250 and 346 million years ago [24].
  • Two Rh polypeptide cDNAs have been isolated from the PCR products and tentatively designated RhPI cDNA and RhPII cDNA [11].
  • The RhPII-1 cDNA had a single nucleotide substitution with one amino acid substitution compared with the RhPII cDNA:substitution C-->T in nucleotide 380, changing codon 127 from GCG to GTG (Ala-->Val) [17].
  • Nucleotide sequencing of RHD exon 5 further revealed three novel alleles RHD(G212G), RHD(R234W), and RHD(V245L), dubbed DUC-1, DQC, and DUC-2 [25].
  • DNA-based rhesus typing: simultaneous determination of RHC and RHD status using the polymerase chain reaction [26].

Analytical, diagnostic and therapeutic context of RHD

  • Foetal DNA typing correctly indicated the RhD in every foetus [15].
  • DNA typing confirmed the RhD-negative type of one AIHA sample in which serological tests were inconclusive [15].
  • The weak D phenotype is caused by many different RHD alleles encoding aberrant RhD proteins, raising the possibility of distinct serologic phenotypes and of anti-D immunizations in weak D [27].
  • Sequence analysis showed that RhK562-II is composed of 951 nucleotides (316 amino acids), identical to the first 939 nucleotides (exons 1 to 6) of one of the Rh(D) cDNAs (RhXIII), except for nucleotide 654 (C-->G exchange) [28].
  • In vitro expression of RhK562-II using the transcription and translation rabbit reticulocyte lysate system produced two major Rh-related proteins (30 kD and 25 kD), which were immunoprecipitated by rabbit polyclonal anti-Rh and separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) [28].


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  6. The RHD gene is highly detectable in RhD-negative Japanese donors. Okuda, H., Kawano, M., Iwamoto, S., Tanaka, M., Seno, T., Okubo, Y., Kajii, E. J. Clin. Invest. (1997) [Pubmed]
  7. Prenatal detection of rhesus D genotype. Hamlington, J., Cunningham, J., Mason, G., Mueller, R., Miller, D. Lancet (1997) [Pubmed]
  8. Production of human monoclonal antibody to rhesus D antigen. Crawford, D.H., Barlow, M.J., Harrison, J.F., Winger, L., Huehns, E.R. Lancet (1983) [Pubmed]
  9. Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist cetrorelix in DU-145 prostate tumor xenografts in nude mice. Lamharzi, N., Halmos, G., Jungwirth, A., Schally, A.V. Int. J. Oncol. (1998) [Pubmed]
  10. Characterization of the hybrid RHD gene leading to the partial D category IIIc phenotype. Beckers, E.A., Faas, B.H., Ligthart, P., Simsek, S., Overbeeke, M.A., von dem Borne, A.E., van Rhenen, D.J., van der Schoot, C.E. Transfusion (1996) [Pubmed]
  11. Isolation of a new cDNA clone encoding an Rh polypeptide associated with the Rh blood group system. Kajii, E., Umenishi, F., Iwamoto, S., Ikemoto, S. Hum. Genet. (1993) [Pubmed]
  12. Molecular analysis of Rh transcripts and polypeptides from individuals expressing the DVI variant phenotype: an RHD gene deletion event does not generate All DVIccEe phenotypes. Avent, N.D., Liu, W., Jones, J.W., Scott, M.L., Voak, D., Pisacka, M., Watt, J., Fletcher, A. Blood (1997) [Pubmed]
  13. In-frame triplet deletions in RHD alter the D antigen phenotype. Flegel, W.A., Eicher, N.I., Doescher, A., Hustinx, H., Gowland, P., Mansouri Taleghani, B., Petershofen, E.K., Bauerfeind, U., Ernst, M., von Zabern, I., Schrezenmeier, H., Wagner, F.F. Transfusion (2006) [Pubmed]
  14. An easy RHD genotyping strategy for D- East Asian persons applied to Korean blood donors. Luettringhaus, T.A., Cho, D., Ryang, D.W., Flegel, W.A. Transfusion (2006) [Pubmed]
  15. Molecular determination of RhD phenotype by DNA typing: clinical applications. Cotorruelo, C., Biondi, C., Borrás, S.G., Galizzi, S., Di Mónaco, R., Racca, A. Ann. Clin. Biochem. (2000) [Pubmed]
  16. Molecular basis of weak D phenotypes. Wagner, F.F., Gassner, C., Müller, T.H., Schönitzer, D., Schunter, F., Flegel, W.A. Blood (1999) [Pubmed]
  17. Molecular analysis of Rh polypeptides in a family with RhD-positive and RhD-negative phenotypes. Umenishi, F., Kajii, E., Ikemoto, S. Biochem. J. (1994) [Pubmed]
  18. Hypermethylated RASSF1A in Maternal Plasma: A Universal Fetal DNA Marker that Improves the Reliability of Noninvasive Prenatal Diagnosis. Chan, K.C., Ding, C., Gerovassili, A., Yeung, S.W., Chiu, R.W., Leung, T.N., Lau, T.K., Chim, S.S., Chung, G.T., Nicolaides, K.H., Lo, Y.M. Clin. Chem. (2006) [Pubmed]
  19. Fetal RhD genotyping from maternal plasma. Lo, Y.M. Ann. Med. (1999) [Pubmed]
  20. Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma. Felix, C.A., Kappel, C.C., Mitsudomi, T., Nau, M.M., Tsokos, M., Crouch, G.D., Nisen, P.D., Winick, N.J., Helman, L.J. Cancer Res. (1992) [Pubmed]
  21. The Rhesus D antigen. A dicyclohexylcarbodiimide-binding proteolipid. Brown, P.J., Evans, J.P., Sinor, L.T., Tilzer, L.T., Plapp, F.V. Am. J. Pathol. (1983) [Pubmed]
  22. Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models. McDowell, H.P., Meco, D., Riccardi, A., Tanno, B., Berardi, A.C., Raschellà, G., Riccardi, R., Dominici, C. Int. J. Cancer (2007) [Pubmed]
  23. Rhesus immunization after renal transplantation. Quan, V.A., Kemp, L.J., Payne, A., Andrews, P.A., Sacks, S.H. Transplantation (1996) [Pubmed]
  24. The members of the RH gene family (RH50 and RH30) followed different evolutionary pathways. Matassi, G., Chérif-Zahar, B., Pesole, G., Raynal, V., Cartron, J.P. J. Mol. Evol. (1999) [Pubmed]
  25. Random survey for RHD alleles among D+ European persons. Chen, Q., Flegel, W.A. Transfusion (2005) [Pubmed]
  26. DNA-based rhesus typing: simultaneous determination of RHC and RHD status using the polymerase chain reaction. Poulter, M., Kemp, T.J., Carritt, B. Vox Sang. (1996) [Pubmed]
  27. Weak D alleles express distinct phenotypes. Wagner, F.F., Frohmajer, A., Ladewig, B., Eicher, N.I., Lonicer, C.B., Müller, T.H., Siegel, M.H., Flegel, W.A. Blood (2000) [Pubmed]
  28. Rh(D) antigen expression and isolation of a new Rh(D) cDNA isoform in human erythroleukemic K562 cells. Suyama, K., Lunn, R., Haller, S., Goldstein, J. Blood (1994) [Pubmed]
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