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Affymetrix Genotyping Array Technology Powers Newly Published Work on Transplantation Genetics

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Affymetrix, Inc. has announced that its Axiom® high-throughput genotyping technology was instrumental in two transplantation peer-reviewed publications issued this month by an international team of surgeons and scientists. The consortium – International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) – co-led by researchers from the Perelman School of Medicine at the University of Pennsylvania, aims to improve transplantation success through the discovery of immunological markers and a deeper understanding of the genomic factors that specifically contribute to graft rejection or other transplant complications. Ultimately, the network aims to apply discoveries of the genomic underpinnings of graft rejection to the clinic in order to improve transplantation success. The first stages of the work, which involved the development and testing of high-density genotyping arrays covering over 780,000 variants, are presented in a pair of papers published this month in Genomic Medicine and the journal Transplantation.  

The first paper, “Concept and Design of a Genome-wide Association Genotyping Array Tailored for Transplantation-Specific Studies,” appears in the October issue of Genomic Medicine and describes development of the array content on the Axiom platform for powerful and cost-effective large-scale genotyping of transplant-related studies. The customized array is comprised of tailored content for deeper capture of variants across human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), pharmacogenomic genes, and metabolic loci important in transplantation. This is the first investigation including non-HLA genetic determinants of clinical outcomes following organ transplantation to date.

Until now, finding donors whose HLA genes are a good match with recipients has been standard practice, but rejection still occurs in a high percentage of transplant patients despite the match. The focus of this new work is on finding additional transplant-related genes; this includes the study of genes that affect the metabolism of immunosuppressant drugs.  

“The genetic datasets we’ve put together in this project are by far the largest ever assembled in transplant genomics,” said Brendan J. Keating, DPhil, a research assistant professor of Transplant Surgery in the Perelman School of Medicine at the University of Pennsylvania.  “Prior to the development of this array, it was not possible to look at all of these markers together.” 

Affymetrix contributed an additional set of ~350,000 SNPs for Caucasian-European and non-European populations to improve the mean coverage achieved in major ethnicities, including African and Asian. These SNPs were chosen with the goal of creating comprehensive overlap with existing data being generated at the UK Biobank using UK Biobank Axiom Array and the Affymetrix Axiom Biobank Array, to enable joint or meta-analyses of samples genotyped  and other conventional GWAS platforms. 

The second publication, “Design and Implementation of the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN),” appears in the October issue of the journal Transplantation and describes the application of this array technology to many more studies and transplantation researchers for a diverse sample base. The consortium has already generated genomic and outcomes data for more than 32,000 organ donors and recipients. Findings from the consortium will provide insights into genomic incompatibility of donor-recipient (D-R) pairs and facilitate improved D-R matching prior to transplantation, as well as identify therapeutic targets and provide information that can be used in the development of personalized immunosuppressive therapies. 

Affymetrix is commercializing the array, which will be used in further studies and to ultimately generate associations that will be applied in personalized and precision-oriented genomic tools to solve clinical questions and improve patient outcomes in transplantation.

“We are pleased to have provided the technology platform for this groundbreaking work,” said Laurent Bellon, Ph.D., senior vice president and general manager, Genotyping Business Unit at Affymetrix. “Affymetrix has commercialized this array, which we are calling the Axiom® Transplant Genotyping Array, and we are introducing it at ASHG this week.”