Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies
| Autor: | Monkol Lek, Samir H Al-Mueilo, Alhusain J. Alzahrani, Kelly A. Thomas, Dimitri S. Monos, Daniel G. MacArthur, Elena Carrigan, Ajay K. Israni, Eyas Mukhtar, Konrad J. Karczewski, Shefali S. Verma, Marylyn D. Ritchie, Brendan J. Keating, Hui Gao, Teresa Webster, Malek Kamoun, Ana Gonzalez, Jessica van Setten, Paul I.W. de Bakker, Laura Steel, Aubree Himes, Kim M. Olthoff, Pamala A. Jacobson, Maede Mohebnasab, Barbara Murphy, Kelsey M. Llyod, Hareesh R. Chandrupatla, Suganthi Balasubramanian, Takesha Lee, James Snyder, Abhinav Gangasani, Baolin Wu, B. Chang, Weihua Guan, Yun Li, Folkert W. Asselbergs, Kelly A. Birdwell, Matthew B. Lanktree, Abraham Shaked, Andrew Pasquier, Cisca Wijmenga, Cuiping Hou, Abigail Colasacco, Chanel Wong, Yontao Lu, Daniel E. McGinn, William S. Oetting, Fahad Al-Muhanna, Amein K. Al-Ali, Abdullah Akdere, Michael B. Miller, Jacob van Houten, David S. Schladt, Hongzhi Cao, Abdullah M. Al-Rubaish, Randy Phillips, Vinicius Tragante, Hakon Hakonarson, Nikhil Nair, Pablo García-Pavía, James Garifallou, Toumy Guettouche, Zach Michaud, Michael V. Holmes, Tiancheng Wang, Reina Yu |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
SNP ARRAY
DNA Copy Number Variations Genotype KIDNEY-TRANSPLANTATION Concordance Population MISMATCH Genome-wide association study 030230 surgery Biology Research Support Polymorphism Single Nucleotide N.I.H 03 medical and health sciences 0302 clinical medicine Receptors KIR Research Support N.I.H. Extramural HLA Antigens MANAGEMENT IMPUTATION Genetics Journal Article Humans Genetics(clinical) International HapMap Project education Non-U.S. Gov't Genotyping Molecular Biology Genetics (clinical) POLYMORPHISMS POPULATION 030304 developmental biology 0303 health sciences education.field_of_study Research Research Support Non-U.S. Gov't Extramural GENE 3. Good health SNP genotyping Transplantation RECIPIENTS REJECTION Molecular Medicine Imputation (genetics) Genome-Wide Association Study |
| Zdroj: | Li, Y R, van Setten, J, Verma, S S, Lu, Y, Holmes, M V, Gao, H, Lek, M, Nair, N, Chandrupatla, H, Chang, B, Karczewski, K J, Wong, C, Mohebnasab, M, Mukhtar, E, Phillips, R, Tragante, V, Hou, C, Steel, L, Lee, T, Garifallou, J, Guettouche, T, Cao, H, Guan, W, Himes, A, van Houten, J, Pasquier, A, Yu, R, Carrigan, E, Miller, M B, Schladt, D, Akdere, A, Gonzalez, A, Llyod, K M, McGinn, D, Gangasani, A, Michaud, Z, Colasacco, A, Snyder, J, Thomas, K, Wang, T, Wu, B, Alzahrani, A J, Al-Ali, A K, Al-Muhanna, F A, Al-Rubaish, A M, Al-Mueilo, S, Monos, D S, Murphy, B, Olthoff, K M, Wijmenga, C, Webster, T, Kamoun, M, Balasubramanian, S, Lanktree, M B, Oetting, W S, Garcia-Pavia, P, MacArthur, D G, de Bakker, P I W, Hakonarson, H, Birdwell, K A, Jacobson, P A, Ritchie, M D, Asselbergs, F W, Israni, A K, Shaked, A & Keating, B J 2015, ' Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies ', Genome Medicine, vol. 7, 90 . https://doi.org/10.1186/s13073-015-0211-x Genome medicine, 7:90. BMC Genome Medicine, 7(1). BioMed Central Genome Medicine |
| ISSN: | 1756-994x 1756-994X |
| Popis: | Background In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods We describe here the design and implementation of a customized genome-wide genotyping array, the ‘TxArray’, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0211-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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