Review article
The Genetics of the Rhesus Blood Group System
Dtsch Arztebl 2007; 104(10): A-651
Introduction: Rhesus blood group antigens are expressed by the RhD and the RhCE proteins. Rhesus is the most important protein-based blood group system, clinically. It comprises the largest number of antigens and the most complex genetics of all 29 known blood group systems. The molecular genetic basis has been elaborated in detail over the last 15 years. Some serological characteristics have been confirmed during this period, where others have been recognized for the first time, using molecular genetic techniques. Methods: Selective literature review. Results: The RHD and the RHCE gene are strongly homologous and located adjacent to one another at chromosome position 1p36.11. Part of the genetic complexity is explained by the unusual orientation of both genes on chromosome 1 with their tail ends facing each other. In the case of Rhesus, molecular polymorphisms can be compared with antigens which have been precisely characterized. Discussion: Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of underlying genetic mechanisms. For clinical purposes, genetic diagnostics of blood group antigens will improve the cost effective development of transfusion medicine. Dtsch Arztebl 2007; 104:(10) A 651–7.
Articles published before 2008 are only available as pdf.
1.
Flegel WA, Wagner FF: Blutgruppen: Alloantigene auf Erythrozyten. In: Mueller-Eckhardt C, Kiefel V, eds.: Transfusionsmedizin. Berlin: Springer; 2003: 145–85.
2.
Howard H, Martlew V, McFadyen I et al.: Censequences for fetus and neonate of maternal red cell allo-immunisation. Arch Dis Child Fetal Neonatal Ed 1998; 78: F62–6. MEDLINE
3.
Bundesärztekammer, Paul-Ehrlich-Institut: Richtlinien zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Hämotherapie) – Gesamtnovelle 2005. Bundesanzeiger 2005; 57(209a): 4–35.
4.
Cichon S, Freudenberg J, Propping P, Nöthen MM: Variabilität im menschlichen Genom. Dtsch Arztebl 2002; 99(46): 3091–101. VOLLTEXT
5.
Wagner FF, Flegel WA: RHD gene deletion occurred in the Rhesus box. Blood 2000; 95: 3662–8. MEDLINE
6.
Aretz S, Propping P, Nöthen MM: Indikationen zur molekulargenetischen Diagnostik bei erblichen Krankheiten. Dtsch Arztebl 2006; 103(9): A550–60. VOLLTEXT
7.
Wagner FF, Frohmajer A, Flegel WA: RHD positive haplotypes in D negative Europeans. BMC Genet 2001; 2: 10. MEDLINE
8.
Wagner FF, Gassner C, Müller TH, Schönitzer D, Schunter F, Flegel WA: Molecular basis of weak D phenotypes. Blood 1999; 93: 385–93. MEDLINE
9.
Shao CP, Maas JH, Su YQ, Köhler M, Legler TJ: Molecular background of Rh D-positive, D-negative, D(el) and weak D phenotypes in Chinese. Vox Sang 2002; 83: 156–61. MEDLINE
10.
Propping P: Genetische Diagnostik vor dem Hintergrund von Millionen Polymorphismen. Dtsch Arztebl 2004; 101(46): 3100–1. VOLLTEXT
11.
Flegel WA, Wagner FF, Müller TH, Gassner C: Rh phenotype prediction by DNA typing and its application to practice. Transfus Med 1998; 8: 281–302. MEDLINE
12.
Wagner FF, Kasulke D, Kerowgan M, Flegel WA: Frequencies of the blood groups ABO, Rhesus, D category VI, Kell, and of clinically relevant high-frequency antigens in South-Western Germany. Infusionsther Transfusionsmed 1995; 22: 285–90. MEDLINE
13.
Wagner FF, Gassner C, Müller TH, Schönitzer D, Schunter F, Flegel WA: Three molecular structures cause Rhesus D category VI phenotypes with distinct immunohematologic features. Blood 1998; 91: 2157–68. MEDLINE
14.
Lippert H-D, Flegel WA: Kommentar zum Transfusionsgesetz (TFG) und den Hämotherapie-Richtlinien. Heidelberg: Springer 2002.
15.
Garratty G: Do we need to be more concerned about weak D antigens? Transfusion 2005; 45: 1547–51. MEDLINE
16.
Gemeinsamer Bundesausschuss: Richtlinien des Bundesausschusses der Ärzte und Krankenkassen über die ärztliche Betreuung während der Schwangerschaft und nach der Entbindung. Bundesanzeiger 1986; 60 a (Beilage), zuletzt geändert: Bundesanzeiger 2003; 126: 14.906.
17.
Lo YMD, Hjelm NM, Fidler C et al.: Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med 1998; 339: 1734–8. MEDLINE
18.
Bianchi DW, Avent ND, Costa JM, van der Schoot CE: Noninvasive prenatal diagnosis of fetal Rhesus D: ready for prime(r) time. Obstet Gynecol 2005; 106: 841–4. MEDLINE
19.
Wagner T, Körmöczi GF, Buchta C et al.: Anti-D immunization by DEL red blood cells. Transfusion 2005; 45: 520–6. MEDLINE
20.
Gassner C, Doescher A, Drnovsek TD et al.: Presence of RHD in serologically D-, C/E+ individuals: a European multicenter study. Transfusion 2005; 45: 527–38. MEDLINE
21.
Yasuda H, Ohto H, Sakuma S, Ishikawa Y: Secondary anti-D immunization by DEL red blood cells. Transfusion 2005; 45: 1581–4. MEDLINE
22.
Flegel WA: Homing in on D antigen immunogenicity. Transfusion 2005; 45: 466–8. MEDLINE
23.
Agre P, Saboori AM, Asimos A, Smith BL: Purification and partial characterization of the Mr 30,000 integral membrane protein associated with the erythrocyte Rh(D) antigen. J Biol Chem 1987; 262: 17497–503. MEDLINE
24.
Marini AM, Matassi G, Raynal V, Andre B, Cartron JP, Cherif-Zahar B: The human Rhesus-associated RhAG protein and a kidney homologue promote ammonium transport in yeast. Nat Genet 2000; 26: 341–4. MEDLINE
25.
Müller TH, Hallensleben M, Schunter F, Blasczyk R: Molekulargenetische Blutgruppendiagnostik. Dtsch Arztebl 2001; 98(6): A317–22. VOLLTEXT
e1.
Filbey D, Hanson U, Wesstrom G: The prevalence of red cell antibodies in pregnancy correlated to the outcome of the newborn: a 12 year study in central Sweden. Acta Obstet Gynecol Scand 1995; 74: 687–92. MEDLINE
e2.
Cheong YC, Goodrick J, Kyle PM, Soothill P: Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998. Fetal Diagn Ther 2001; 16: 294–8. MEDLINE
e3.
Wagner FF, Eicher NI, Jorgensen JR, Lonicer CB, Flegel WA: DNB: a partial D with anti-D frequent in Central Europe. Blood 2002; 100: 2253–6. MEDLINE
e4.
Wagner FF, Flegel WA: RHCE represents the ancestral RH position, while RHD is the duplicated gene. Blood 2002; 99: 2272–3. MEDLINE
e5.
Flegel WA: How I manage donors and patients with a weak D phenotype. Curr Opin Hematol 2006; 13: 476–83. MEDLINE
e6.
Wagner FF, Frohmajer A, Ladewig B et al.: Weak D alleles express distinct phenotypes. Blood 2000; 95: 2699–708. MEDLINE
e7.
Flegel WA: The Rhesus Site. DRK-Blutspendedienst Baden-Württemberg-Hessen. 1998–2007. www.uni-ulm.de/~wflegel/RH/
e8.
Northoff H, Flegel WA: Genotyping and phenotyping: the two sides of one coin. Infusionsther Transfusionsmed 1999; 26: 5.
