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Whole Genome Sequencing for Blood Group Genotyping and Definition as Exemplified on U- and St(a)+. (Blood Genome)

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ClinicalTrials.gov Identifier: NCT02534519
Recruitment Status : Unknown
Verified August 2015 by Christoph Gassner, Blood Donation Service Zurich, SRC.
Recruitment status was:  Recruiting
First Posted : August 27, 2015
Last Update Posted : August 27, 2015
Sponsor:
Information provided by (Responsible Party):
Christoph Gassner, Blood Donation Service Zurich, SRC

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment
Genetic Blood Group (bg) Polymorphism in U Negativity and St(a) of MNSs Other: Whole Genome Sequencing (WGS)

Detailed Description:

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.

Study Design
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Study Type : Observational [Patient Registry]
Estimated Enrollment : 8 participants
Observational Model: Case-Control
Target Follow-Up Duration: 1 Day
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)+
Study Start Date : July 2015
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : June 2018
Groups and Cohorts
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Group/Cohort Intervention/treatment
people negative in bg MNSs antigen U
Blood group (bg) system MNSs. Individuals with phenotype "U-". Homo- and heterozygous individuals may be considered.
 Other: Whole Genome Sequencing (WGS)
There will be no interventions needed other than blood sampling (20 mL blood) in the course of routine blood donation (450 mL blood) for 8 out of 10 individuals planned to be included as specimen, or reference samples in the study.
people positive in bg MNSs antigen St(a)
Blood group (bg) system MNSs. Individuals with phenotype "St(a)+". Homo- and heterozygous individuals may be considered.
 Other: Whole Genome Sequencing (WGS)
There will be no interventions needed other than blood sampling (20 mL blood) in the course of routine blood donation (450 mL blood) for 8 out of 10 individuals planned to be included as specimen, or reference samples in the study.


Outcome Measures
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Primary Outcome Measures :
  1. Whole Genome Sequencing for the definition of genetic background for blood group antigens U-, St(a)+ [ Time Frame: 2 year period ]
    During a 2 year time-period, whole genome sequencing data generation and analysis will be used for the analysis and description of the genetic background for the blood group antigens U negativity, and for St(a).


Biospecimen Retention:   Samples With DNA
Two times 10 mL EDTA-anticoagulated whole blood and genomic DNA resulting from this amount.

Eligibility Criteria
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Ages Eligible for Study:   1 Year to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
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
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02534519


Contacts
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Contact: Christoph Gassner, PhD +41 58 272 5195 c.gassner@zhbsd.ch

Locations
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Switzerland
Blutpende Zürich, Dienstleistungszentrum Recruiting
Schlieren, Zürich, Switzerland, 8952
Contact: Christoph Gassner, PhD    +41 58 272 5195    c.gassner@zhbsd.ch   
Sponsors and Collaborators
Blood Donation Service Zurich, SRC
Investigators
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Principal Investigator: Christoph Gassner, PhD Blutspende Zürich, Dienstleistungszentrum
More Information
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Additional Information:

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Responsible Party: Christoph Gassner, Priv. Doz. Mag. Dr. rer. nat. Christoph Gassner, Blood Donation Service Zurich, SRC
ClinicalTrials.gov Identifier: NCT02534519    
Other Study ID Numbers: KEK-ZH-Nr. 2014-0408
First Posted: August 27, 2015    Key Record Dates
Last Update Posted: August 27, 2015
Last Verified: August 2015