Whole Genome Sequencing for Blood Group Genotyping and Definition as Exemplified on U- and St(a)+.
Whole Genome Sequencing for Blood Group Genotyping and Definition as Exemplified on U- and St(a)+.
No health condition(s) are studied. Genetic background of blood groups is studied. U- and
 Stones(a)+ ("Caucasian type") are used as proof-of-principle samples. Disease associations of
 all blood group genes investigated are very rare, e.g. < 1 among 1'000 Swiss individuals (see
 table 1), and are not to be expected in the course of this study.

 Genomic DNA of 2 U- samples were both provided as blinded reference material from New York
 and Vienna blood centres, respectively. Both donors are lost for follow up, and although
 there is no documented evidence for refusal of the respective donors to use their material in
 research projects, samples still lack informed consent.
All 34 human blood group systems have at least two antithetical antigens and are of potential
 relevance during pregnancy and transfusion. Fortunately for every day routine practice,
 immunizations to foreign antigens are rare. Still, incompatibilities may occur in all blood
 group systems and will then require typing for the respective blood group antigens.

 Blood genotyping evolved as the method of choice, in cases when typing reagents are
 commercially unavailable, or blood is inaccessible (foetus). In databases, most entries of
 blood group genes lack representative polymorphism (e.g. number of alleles). Moreover, many
 blood group antigens are insufficiently described in their intronic and inter-genetic
 sequences. This is true for results of unequal crossing-overs, gene-conversions and large
 insertions/deletions between highly homologous genes, especially within the blood group
 systems of Rhesus, e.g. RhD/RhCE and MN/Ss, respectively. Only Whole Genome Sequencing (WGS)
 allows for resolution of both problems: it delivers the whole blood group genome of an
 individual, and simultaneously recognizes new blood group alleles, or haplotypes. This
 request for ethical approval wants to test this assumption.

 The antigenic determinants U- and Stones(a)+ of the blood group system MNSs still lack full
 genetic description and will serve as challenging examples for the description of new alleles
 (haplotypes) caused by large ins/del mutations of the two highly homologous genes GYPA and B.
 Genomic DNA of 2 U- samples were both provided as blinded reference material from New York
 and Vienna blood centres, respectively. Both donors are lost for follow up, and although
 there is no documented evidence for refusal of the respective donors to use their material in
 research projects, samples still lack informed consent. Additional reference samples (n
 max=4), and samples with suspected Stones(a)+ (n max=4) will be recruited from Zurich blood
 donors with informed consent, only.
Inclusion Criteria:

 -  Existing biomaterial (gDNA), or

 -  Existing health related data for blood group U- (n max=2) and eligible for (venous)
 blood sampling of 20 mL, or

 -  Existing blood group pheno- and genotyping data indicating St(a)+ and eligible for
 (venous) blood sampling of 20 mL (n max=2), or

 -  Adequate blood group profile serving as reference (n max =4 & n max =4'000) and
 eligible for (venous) blood sampling of 20 mL.

 Exclusion Criteria:

 -  Ineligible for venous blood sampling of approx. 20 mL.