High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies.

Frontiers in Immunology
Anja KlussmeierVinzenz Lange

Abstract

MICA and MICB are ligands of the NKG2D receptor and thereby influence NK and T cell activity. MICA/B gene polymorphisms, expression levels and the amount of soluble MICA/B in the serum have been linked to autoimmune diseases, infections, and cancer. In hematopoietic stem cell transplantation, MICA matching between donor and patient has been correlated with reduced acute and chronic graft-vs.-host disease and improved survival. Hence, we developed an extremely cost-efficient high-throughput workflow for genotyping MICA/B for newly registered potential stem cell donors. Since mid-2017, we have genotyped over two million samples using NGS amplicon sequencing for MICA/B exons 2-5. In donors of German origin, MICA*008 is the most common MICA allele with a frequency of 42.3%. It is followed by MICA*002 (11.7%) and MICA*009 (8.8%). The three most common MICB alleles are MICB*005 (43.9%), MICB*004 (21.7%), and MICB*002 (18.9%). In general, MICB is less diverse than MICA and only 6 alleles, instead of 15, account for a cumulative allele frequency of 99.5%. In 0.5% of the samples we observed at least one allele of MICA or MICB which has so far not been reported to the IPD/IMGT-HLA database. By providing MICA/B typed voluntary donors, cli...Continue Reading

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Citations

Sep 15, 2020·Biospektrum : Zeitschrift Der Gesellschaft Für Biologishe Chemie (GBCH) Und Der Vereinigung Für Allgemeine Und Angewandte Mikrobiologie (VAAM)·Anja KlussmeierVinzenz Lange
Apr 1, 2020·Frontiers in Immunology·Ute V SollochJürgen Sauter
Feb 3, 2021·HLA : Immune Response Genetics·Christin PaechAnja Klussmeier
Apr 25, 2021·Human Immunology·Yuxin YinQiuheng Zhang

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Methods Mentioned

BETA
genotyping
PCR
Assay

Software Mentioned

IPD
neXtype
IMGT
HLA

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