Development and evaluation of a transfusion medicine genome wide genotyping array.
Busch, Michael P
Westhoff, Connie M
Mast, Alan E
Page, Grier P
National Heart, Lung, and Blood Institute Recipient Epidemiology Donor Evaluation Study (REDS)-III
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Guo, Y., Busch, M. P., Seielstad, M., Endres-Dighe, S., Westhoff, C. M., Keating, B., Hoppe, C., et al. (2019). Development and evaluation of a transfusion medicine genome wide genotyping array.. Transfusion, 59 (1), 101-111. https://doi.org/10.1111/trf.15012
BACKGROUND: Many aspects of transfusion medicine are affected by genetics. Current single-nucleotide polymorphism (SNP) arrays are limited in the number of targets that can be interrogated and cannot detect all variation of interest. We designed a transfusion medicine array (TM-Array) for study of both common and rare transfusion-relevant variations in genetically diverse donor and recipient populations. STUDY DESIGN AND METHODS: The array was designed by conducting extensive bioinformatics mining and consulting experts to identify genes and genetic variation related to a wide range of transfusion medicine clinical relevant and research-related topics. Copy number polymorphisms were added in the alpha globin, beta globin, and Rh gene clusters. RESULTS: The final array contains approximately 879,000 SNP and copy number polymorphism markers. Over 99% of SNPs were called reliably. Technical replication showed the array to be robust and reproducible, with an error rate less than 0.03%. The array also had a very low Mendelian error rate (average parent-child trio accuracy of 0.9997). Blood group results were in concordance with serology testing results, and the array accurately identifies rare variants (minor allele frequency of 0.5%). The array achieved high genome-wide imputation coverage for African-American (97.5%), Hispanic (96.1%), East Asian (94.6%), and white (96.1%) genomes at a minor allele frequency of 5%. CONCLUSIONS: A custom array for transfusion medicine research has been designed and evaluated. It gives wide coverage and accurate identification of rare SNPs in diverse populations. The TM-Array will be useful for future genetic studies in the diverse fields of transfusion medicine research.
National Heart, Lung, and Blood Institute Recipient Epidemiology Donor Evaluation Study (REDS)-III, Humans, Computational Biology, Gene Frequency, Genotype, Polymorphism, Single Nucleotide, Genome, Human, African Americans, Asian Continental Ancestry Group, European Continental Ancestry Group, Genome-Wide Association Study, Transfusion Medicine
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
External DOI: https://doi.org/10.1111/trf.15012
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282948