Genetic Blood Group (bg) Polymorphism in U Negativity and St(a) of MNSs Clinical Trial
Official title:
Applicability of Whole Genome Sequencing for Human Blood Group Genotyping and Genetic Definition of New Alleles as Exemplified on References and the Two MNSs-variants: U- and Stones(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.
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Observational Model: Case Control