Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies.

Li, Yun R and van Setten, Jessica and Verma, Shefali S and Lu, Yontao and Holmes, Michael V and Gao, Hui and Lek, Monkol and Nair, Nikhil and Chandrupatla, Hareesh and Chang, Baoli and Karczewski, Konrad J and Wong, Chanel and Mohebnasab, Maede and Mukhtar, Eyas and Phillips, Randy and Tragante, Vinicius and Hou, Cuiping and Steel, Laura and Lee, Takesha and Garifallou, James and Guettouche, Toumy and Cao, Hongzhi and Guan, Weihua and Himes, Aubree and van Houten, Jacob and Pasquier, Andrew and Yu, Reina and Carrigan, Elena and Miller, Michael B and Schladt, David and Akdere, Abdullah and Gonzalez, Ana and Llyod, Kelsey M and McGinn, Daniel and Gangasani, Abhinav and Michaud, Zach and Colasacco, Abigail and Snyder, James and Thomas, Kelly and Wang, Tiancheng and Wu, Baolin and Alzahrani, Alhusain J and Al-Ali, Amein K and Al-Muhanna, Fahad A and Al-Rubaish, Abdullah M and Al-Mueilo, Samir and Monos, Dimitri S and Murphy, Barbara and Olthoff, Kim M and Wijmenga, Cisca and Webster, Teresa and Kamoun, Malek and Balasubramanian, Suganthi and Lanktree, Matthew B and Oetting, William S and Garcia-Pavia, Pablo and MacArthur, Daniel G and de Bakker, Paul IW and Hakonarson, Hakon and Birdwell, Kelly A and Jacobson, Pamala A and Ritchie, Marylyn D and Asselbergs, Folkert W and Israni, Ajay K and Shaked, Abraham and Keating, Brendan J (2015) Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies. Genome Med, 7. 90 - ?.

Preview	PDF Available under License : See the attached license file. Download (1MB) | Preview
	Plain Text (licence) Available under License : See the attached license file. Download (1kB)

Abstract

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.

---

Share

Citation/Export:	Select format... Citation - Text Citation - HTML Endnote BibTex Dublin Core OpenURL MARC (ISO 2709) METS MODS EP3 XML Reference Manager Refer
Social Networking:	Share |

---

Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Li, Yun R van Setten, Jessica Verma, Shefali S Lu, Yontao Holmes, Michael V Gao, Hui Lek, Monkol Nair, Nikhil Chandrupatla, Hareesh Chang, Baoli Karczewski, Konrad J Wong, Chanel Mohebnasab, Maede MAM1236@pitt.edu MAM1236 0000-0001-6623-9514 Mukhtar, Eyas Phillips, Randy Tragante, Vinicius Hou, Cuiping Steel, Laura Lee, Takesha Garifallou, James Guettouche, Toumy Cao, Hongzhi Guan, Weihua Himes, Aubree van Houten, Jacob Pasquier, Andrew Yu, Reina Carrigan, Elena Miller, Michael B Schladt, David Akdere, Abdullah Gonzalez, Ana Llyod, Kelsey M McGinn, Daniel Gangasani, Abhinav Michaud, Zach Colasacco, Abigail Snyder, James Thomas, Kelly Wang, Tiancheng Wu, Baolin Alzahrani, Alhusain J Al-Ali, Amein K Al-Muhanna, Fahad A Al-Rubaish, Abdullah M Al-Mueilo, Samir Monos, Dimitri S Murphy, Barbara Olthoff, Kim M Wijmenga, Cisca Webster, Teresa Kamoun, Malek Balasubramanian, Suganthi Lanktree, Matthew B Oetting, William S Garcia-Pavia, Pablo MacArthur, Daniel G de Bakker, Paul IW Hakonarson, Hakon Birdwell, Kelly A Jacobson, Pamala A Ritchie, Marylyn D Asselbergs, Folkert W Israni, Ajay K Shaked, Abraham Keating, Brendan J
Date:	28 July 2015
Date Type:	Acceptance
Journal or Publication Title:	Genome Med
Volume:	7
Page Range:	90 - ?
DOI or Unique Handle:	10.1186/s13073-015-0211-x
Schools and Programs:	School of Medicine > Pathology
Refereed:	Yes
Uncontrolled Keywords:	DNA Copy Number Variations, Genome-Wide Association Study, Genotype, HLA Antigens, Humans, Polymorphism, Single Nucleotide, Receptors, KIR
Funders:	NIAID NIH HHS (U01 AI063589), NIAID NIH HHS (UM1 AI109565), NIAID NIH HHS (U01-AI63589), NIAID NIH HHS (U19 AI070119), NIAID NIH HHS (UM1AI109565), NIDDK NIH HHS (U01-DK062494), NIDDK NIH HHS (U01 DK062494), NIAID NIH HHS (U19-AI070119), NHGRI NIH HHS (U01 HG006830)
Date Deposited:	29 Aug 2022 15:35
Last Modified:	06 Sep 2022 13:55
URI:	http://d-scholarship.pitt.edu/id/eprint/43678

---

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

---

Actions (login required)

View Item