Mathematics and transfusion medicine - Blood Transfusion

Flegel W Athis would be likely to result in Rhesus haemolytic diseaseof the newborn.The function of Rhesus proteinsMost blood group proteins have a known function.While purifying human Rhesus proteins, Americanphysician Peter Agre discovered a water transporterprotein 28 . This discovery earned him the 2003 Nobel Prizefor Chemistry. Despite intensive efforts, however, nofunction has been found for the RhD and RhCE proteins.Although the Rhesus associated antigen (RhAG), a Rhesushomologue contained in erythrocytes, can transportammonium ions 29 , the Rhesus proteins themselves couldnot be shown to have any such function. One possiblefunction under investigation involves the exchange of CO 2and even O 2. Other information on the RH alleles will onlybe gained from the everyday clinical application of geneticdiagnostics, which could thus contribute to identifyingtheir function.From the perspective of basic research, wheretransfusion medicine will continue to make a contribution,scientific work on Rhesus 30 and other blood groups hasbeen quite productive, and is anything but finished.OutlookGenetic diagnosis has been used for blood group typingin clinical transfusion medicine ever since 2000 31,32 . Asantenatal care has shown, genetic blood group typing hasled to a better quality of care, by helping to avoid potentialside effects and reducing costs. This is a rare combination,and justifies the extra costs involved in optimizing care viathe use of genetic diagnostic techniques. As well asimproving patient care, these methods can fuel thedevelopment of new methods 14 , which will also be used forhealth care outside of Germany. European departments oftransfusion medicine are leading the field in molecular bloodgroup diagnostics and applications, and will continue tocontribute to improving patient care.Common Genome Variability Terms 4,6SNP (single nucleotide polymorphism)Point mutation. Variability in a nucleotide sequence dueto change of a single nucleotide.AlleleThe expression of a coding or non coding nucleotidesequence (the exon resp. intron of a gene) with two ormore variants, often differing by only a point mutation.GenotypeA pair of alleles or variants of a nucleotide sequenceoccurring at homologous sites on paired chromosomes.HaplotypeA combination of alleles or variants of a nucleotidesequence located close together on the samechromosome, and usually inherited together.Missense mutationAmino acid substitution in a protein caused by a pointmutation. It can alter the function or antigenicity of aprotein.Nonsense mutationA stop codon caused by a point mutation whichprematurely stops synthesis of the amino acid chain,leading to loss of protein function of its expression.Silent mutationA point mutation which does not change the aminoacid at the site. Although the protein is unchanged, itstill can be associated with a clinically relevantphenotype and be used diagnostically.Frame shift mutationThe loss or insertion of one or two nucleotides whichshifts the reading frame and prematurely stops proteinsynthesis (or extends it in some rare cases), resulting inloss of protein function or expression.Splice site mutationA point mutation at a splice site (the exon-intronjunction), causing faulty splicing of messenger RNA(mRNA) and skipping an exon, thus changing the aminoacid sequence. Leads to loss of protein function orexpression.Gene conversionThe non-reciprocal exchange between two or morehomologous genes, whereby a certain nucleotidesequence on a gene is substituted by a sequence onanother gene, which is located on the same chromosome(conversion in cis).AcknowledgementsThis article is published by the courtesy of ChristopherBaethge, M.D., Editor in Chief of the journal DeutschesÄrzteblatt. This English translation was provided by thejournal Deutsches Ärzteblatt.Key Word: Rhesus, blood group, molecular diagnostic,transfusion, pregnancy.References1) Flegel WA, Wagner FF. Blutgruppen: Alloantigene aufErythrozyten. In: Mueller-Eckhardt C, Kiefel V, eds.:Transfusionsmedizin. Berlin, Berlin Springer; 2003: p. 145-85.2) Howard H, Martlew V, McFadyen I, et al. Consequences for56Blood Transfus 2007; 5: 50-57050-57_flegel.p65 5605/07/2007, 10.34