Development and evaluation of a transfusion medicine genome wide genotyping array

Liliana R. Preiss; Daniel C. Ringer; Marian T. Sullivan; Christopher R. McClure; Donald James Brambilla; Grier Philip Page; Bruce Christopher Siege; Stacy Michelle Endres; Shelly Jones Johnson; Yuelong John Guo; Nana Yaa Haywood; L. M. Anderson; John L. Miller; Yuelong John Guo; Michael P. Busch; Mark Seielstad; Stacy M  Endres-Dighe; Connie M Westhoff; Brendan Keating; Carolyn Hoppe; Aarash Bordbar; Brian Custer; Adam S Butterworth; Tamir Kanias; Alan E Mast; Steve Kleinman; Yontao Lu; Grier Philip Page; A. E. Mast; J L Gottschall; W Bialkowski; L. M. Anderson; John L. Miller; A. Hall; Z. Udee; V Johnson; D J Triulzi; Joseph E Kiss; P. A. D'Andrea; E L Murphy; A. M. Guiltinan; Ritchard G Cable; Bryan R. Spencer; Shelly Jones Johnson; Don Brambilla; Marian T. Sullivan; Stacy M  Endres-Dighe; Grier Philip Page; Yuelong John Guo; Nana Yaa Haywood; Daniel C. Ringer; Christopher Siege; Michael P. Busch; M. C. Lanteri; M Stone; SM Keating; T Kanias; Don Brambilla; Marian T. Sullivan; Grier Philip Page; Yuelong John Guo; Liliana R. Preiss; Christopher R. McClure

Development and evaluation of a transfusion medicine genome wide genotyping array

Guo, Y., Busch, M. P., Seielstad, M., Endres-Dighe, S., Westhoff, C. M., Keating, B., Hoppe, C., Bordbar, A., Custer, B., Butterworth, A. S., Kanias, T., Mast, A. E., Kleinman, S., Lu, Y., Page, G. P., Mast, A. E., Gottschall, J. L., Bialkowski, W., Anderson, L., ... Natl Heart Lung Blood Inst (2019). Development and evaluation of a transfusion medicine genome wide genotyping array. Transfusion, 59(1), 101-111. Article Trans-2018-0144.R1. https://doi.org/10.1111/trf.15012

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Abstract

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.