Multiple GYPB gene deletions associated with the U- phenotype in those of African ancestry.

Autor: Lane WJ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Gleadall NS; Department of Haematology, University of Cambridge, Cambridge, UK.; NHS Blood and Transplant, Cambridge, UK., Aeschlimann J; New York Blood Center, New York, New York., Vege S; New York Blood Center, New York, New York., Sanchis-Juan A; Department of Haematology, University of Cambridge, Cambridge, UK.; NHS Blood and Transplant, Cambridge, UK.; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Stephens J; Department of Haematology, University of Cambridge, Cambridge, UK.; NHS Blood and Transplant, Cambridge, UK.; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Sullivan JC; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Mah HH; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Aguad M; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Smeland-Wagman R; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Lebo MS; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Laboratory for Molecular Medicine, Boston, Massachusetts.; Partners Personalized Medicine, Boston, Massachusetts., Vijay Kumar PK; Partners Personalized Medicine, Boston, Massachusetts., Kaufman RM; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Green RC; Harvard Medical School, Boston, Massachusetts.; Partners Personalized Medicine, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Boston, Massachusetts.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Ouwehand WH; Department of Haematology, University of Cambridge, Cambridge, UK.; NHS Blood and Transplant, Cambridge, UK.; Wellcome Sanger Institute, Cambridge, UK., Westhoff CM; New York Blood Center, New York, New York.
Jazyk: angličtina
Zdroj: Transfusion [Transfusion] 2020 Jun; Vol. 60 (6), pp. 1294-1307. Date of Electronic Publication: 2020 May 30.
DOI: 10.1111/trf.15839
Abstrakt: Background: The MNS blood group system is defined by three homologous genes: GYPA, GYPB, and GYPE. GYPB encodes for glycophorin B (GPB) carrying S/s and the "universal" antigen U. RBCs of approximately 1% of individuals of African ancestry are U- due to absence of GPB. The U- phenotype has long been attributed to a deletion encompassing GYPB exons 2 to 5 and GYPE exon 1 (GYPB*01N).
Study Design and Methods: Samples from two U-individuals underwent Illumina short read whole genome sequencing (WGS) and Nanopore long read WGS. In addition, two existing WGS datasets, MedSeq (n = 110) and 1000 Genomes (1000G, n = 2535), were analyzed for GYPB deletions. Deletions were confirmed by Sanger sequencing. Twenty known U- donor samples were tested by a PCR assay to determine the specific deletion alleles present in African Americans.
Results: Two large GYPB deletions in U- samples of African ancestry were identified: a 110 kb deletion extending left of GYPB (DEL_B_LEFT) and a 103 kb deletion extending right (DEL_B_RIGHT). DEL_B_LEFT and DEL_B_RIGHT were the most common GYPB deletions in the 1000 Genomes Project 669 African genomes (allele frequencies 0.04 and 0.02). Seven additional deletions involving GYPB were seen in African, Admixed American, and South Asian samples. No samples analyzed had GYPB*01N.
Conclusions: The U- phenotype in those of African ancestry is primarily associated with two different complete deletions of GYPB (with intact GYPE). Seven additional less common GYPB deletion backgrounds were found. GYPB*01N, long assumed to be the allele commonly encoding U- phenotypes, appears to be rare.
(© 2020 AABB.)
Databáze: MEDLINE
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