title: MNSs genotyping by MALDI-TOF MS shows high concordance with serology, allows gene copy number testing and reveals new St(a) alleles.
abstract: Results of genotyping with true high-throughput capability for MNSs antigens are underrepresented, probably because of technical issues, due to the high level of nucleotide sequence homology of the paralogous genes GYPA, GYPB and GYPE. Eight MNSs-specific single nucleotide polymorphisms (SNP) were detected using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS) in 5800 serologically M/N and S/s pre-typed Swiss blood donors and 50 individuals of known or presumptive black African ethnicity. Comparison of serotype with genotype delivered concordance rates of 99·70% and 99·90% and accuracy of genotyping alone of 99·88% and 99·95%, for M/N and S/s, respectively. The area under the curve of peak signals was measured in intron 1 of the two highly homologous genes GYPB and GYPE and allowed for gene copy number variation estimates in all individuals investigated. Elevated GYPB:GYPE ratios accumulated in several carriers of two newly observed GYP*401 variants, termed type G and H, both encoding for the low incidence antigen St(a). In black Africans, reduced GYPB gene contents were proven in pre-typed S-s-U- phenotypes and could be reproduced in unknown specimens. Quantitative gene copy number estimates represented a highly attractive supplement to conventional genotyping, solely based on MNSs SNPs.
authors.affiliation: Blood Transfusion Service Zürich, Department of Molecular Diagnostics & Research (MOC), Swiss Red Cross (SRC), Zürich, Schlieren, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Agena Bioscience GmbH, Hamburg, Germany.
authors.forename: Caren
authors.initials: C
authors.lastname: Vollmert
authors.affiliation: Blood Transfusion Service Zürich, Department of Molecular Diagnostics & Research (MOC), Swiss Red Cross (SRC), Zürich, Schlieren, Switzerland.
authors.forename: Nadine
authors.initials: N
authors.lastname: Trost
authors.affiliation: Blood Transfusion Service Zürich, Department of Molecular Diagnostics & Research (MOC), Swiss Red Cross (SRC), Zürich, Schlieren, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sigurdardottir
authors.affiliation: Blood Transfusion Service Zürich, Department of Molecular Diagnostics & Research (MOC), Swiss Red Cross (SRC), Zürich, Schlieren, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Portmann
authors.affiliation: Blood Transfusion Service Zürich, SRC, Schlieren, Switzerland.
authors.forename: Jochen
authors.initials: J
authors.lastname: Gottschalk
authors.affiliation: Blood Transfusion Service Zürich, SRC, Schlieren, Switzerland.
authors.forename: Judith
authors.initials: J
authors.lastname: Ries
authors.affiliation: Blood Transfusion Service Zürich, SRC, Schlieren, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Markovic
authors.affiliation: Blood Transfusion Service beider Basel, SRC, Basel, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Infanti
authors.affiliation: Blood Transfusion Service beider Basel, SRC, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.affiliation: Blood Transfusion Service Genève, SRC, Geneva, Switzerland.
authors.forename: Soraya
authors.initials: S
authors.lastname: Amar El Dusouqui
authors.affiliation: Blood Transfusion Service Genève, SRC, Geneva, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rigal
authors.affiliation: Blood Transfusion Service Svizzera Italiana, SRC, Lugano, Switzerland.
authors.forename: Damiano
authors.initials: D
authors.lastname: Castelli
authors.affiliation: Blood Transfusion Service Zentralschweiz, SRC, Lucerne, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Weingand
authors.affiliation: Blood Transfusion Service Zentralschweiz, SRC, Lucerne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maier
authors.affiliation: Blood Transfusion Service Neuchâtel-Jura, SRC, Neuchâtel, Switzerland.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Mauvais
authors.affiliation: Blood Transfusion Service Neuchâtel-Jura, SRC, Neuchâtel, Switzerland.
authors.forename: Amira
authors.initials: A
authors.lastname: Sarraj
authors.affiliation: Blood Transfusion Service Ostschweiz, SRC, St. Gallen, Switzerland.
authors.forename: Monica C
authors.initials: MC
authors.lastname: Braisch
authors.affiliation: Blood Transfusion Service Ostschweiz, SRC, St. Gallen, Switzerland.
authors.forename: Jutta
authors.initials: J
authors.lastname: Thierbach
authors.affiliation: Interregional Blood Transfusion, SRC, Ltd., Bern, Switzerland.
authors.forename: Hein
authors.initials: H
authors.lastname: Hustinx
authors.affiliation: Blood Transfusion Service Zürich, SRC, Schlieren, Switzerland.
authors.forename: Beat M
authors.initials: BM
authors.lastname: Frey
authors.affiliation: Blood Transfusion Service Zürich, Department of Molecular Diagnostics & Research (MOC), Swiss Red Cross (SRC), Zürich, Schlieren, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gassner
mesh_terms: D000483:Alleles; D044383:Black People; D001789:Blood Group Antigens / Q000235:genetics*; D005006:Ethnicity; D018628:Gene Dosage; D005838:Genotype; D006021:Glycophorins / Q000235:genetics; D006801:Humans; D008951:MNSs Blood-Group System / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D001789:Blood Group Antigens; C409972:GYPA protein, human; C409973:GYPB protein, human; D006021:Glycophorins; D008951:MNSs Blood-Group System
keywords: GYPA; GYPB; MALDI-TOF MS; MNSs alleles; MNSs antigens; blood group genotyping