Guo Yuelong, Busch Michael P, Seielstad Mark, Endres-Dighe Stacy, Westhoff Connie M, Keating Brendan, Hoppe Carolyn, Bordbar Aarash, Custer Brian, Butterworth Adam S, Kanias Tamir, Mast Alan E, Kleinman Steve, Lu Yontao, Page Grier P
RTI International, Research Triangle Park, North Carolina.
Vitalant Research Institute (formerly Blood Systems Research Institute), San Francisco, California.
Transfusion. 2019 Jan;59(1):101-111. doi: 10.1111/trf.15012. Epub 2018 Nov 20.
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.
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.
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%.
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.
输血医学的许多方面都受到遗传学的影响。当前的单核苷酸多态性（SNP）阵列在可检测的目标数量上有限，并且无法检测到所有感兴趣的变异。我们设计了一种输血医学阵列（TM-Array），用于研究遗传背景多样的供体和受体群体中常见和罕见的输血相关变异。
通过广泛的生物信息学挖掘和咨询专家来设计该阵列，以识别与广泛的输血医学临床相关和研究相关主题相关的基因和遗传变异。在α珠蛋白、β珠蛋白和Rh基因簇中添加了拷贝数多态性。
最终的阵列包含约879,000个SNP和拷贝数多态性标记。超过99%的SNP能够可靠地被检测到。技术重复显示该阵列稳健且可重复，错误率低于0.03%。该阵列的孟德尔错误率也非常低（亲子三联体平均准确率为0.9997）。血型结果与血清学检测结果一致，并且该阵列能够准确识别罕见变异（次要等位基因频率为0.5%）。在次要等位基因频率为5%时，该阵列在非裔美国人（97.5%）、西班牙裔（96.1%）、东亚人（94.6%）和白人（96.1%）基因组中实现了高全基因组归因覆盖率。
已设计并评估了一种用于输血医学研究的定制阵列。它在不同人群中对罕见SNP具有广泛的覆盖范围和准确的识别能力。TM-Array将有助于未来输血医学研究各个领域的遗传学研究。
