Transplant genetics and genomics

Yang, Joshua; Sarwal, Minnie M.

doi:10.1038/nrg.2017.12

Cited by 64 publications

(57 citation statements)

References 209 publications

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“…Additional omics data, such as RNA or protein expression, may also be used to assess compatibility of donor–recipient pairs, as well as monitor for markers of rejection (for a recent review, see REF. 131). Integration across multiple omics technologies may well emerge as a useful tool for transplant biology.…”

Section: Challengesmentioning

confidence: 99%

Integrative omics for health and disease

2018

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Advances in omics technologies — such as genomics, transcriptomics, proteomics and metabolomics — have begun to enable personalized medicine at an extraordinarily detailed molecular level. Individually, these technologies have contributed medical advances that have begun to enter clinical practice. However, each technology individually cannot capture the entire biological complexity of most human diseases. Integration of multiple technologies has emerged as an approach to provide a more comprehensive view of biology and disease. In this Review, we discuss the potential for combining diverse types of data and the utility of this approach in human health and disease. We provide examples of data integration to understand, diagnose and inform treatment of diseases, including rare and common diseases as well as cancer and transplant biology. Finally, we discuss technical and other challenges to clinical implementation of integrative omics.

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Section: Challengesmentioning

confidence: 99%

Integrative omics for health and disease

2018

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“…GWASs have been applied to numerous hematologic endpoints and have advanced our knowledge of the genetic underpinnings of modifiers of complete blood count, hematopoiesis, cardiovascular diseases, and sickle cell anemia . Transplant research has benefitted from GWASs by identifying novel genes and alleles that are associated with kidney transplant rejection and clinical outcomes in patients with renal and lung transplants . Although advances in whole genome sequencing have made it possible to interrogate causal variants directly as opposed to evaluating variants that are in linkage disequilibrium with causal variants, array‐based genotyping remains a cost‐effective method for genotyping large cohorts, such as the UK Biobank cohort, in which half a million participants have been enrolled and genotyped .…”

mentioning

confidence: 99%

Development and evaluation of a transfusion medicine genome wide genotyping array

et al. 2018

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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 transfusionmedicine 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. T ransfusion medicine encompasses diverse medical services and fields of research including blood donation, component processing, immunohematology, infectious disease, recipient outcomes, ABBREVIATIONS: BGMUT = blood group antigen gene mutation; CNPs = copy number polymorphisms; GWASs = genome-wide association studies; MAF = minor allele frequency; NHLBI = National Heart, Lung, and Blood Institute; RBC-Omics = Red Blood Cell Omics; REDS-III = Recipient Epidemiology Donor Evaluation Study-III; SCD = sickle cell disease; SNP = single-nucleotide polymorphism

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“…Germline variants exert strong effects on circulating leukocyte counts (Keller et al, 2014) and on leukocyte fractions (Orru et al, 2013). Immune-mediated tissue rejection in organ or bone marrow transplantation (Yang and Sarwal, 2017) and autoimmunity (Ye et al, 2018) have been associated with common germline variations in genome-wide association studies (GWAS).…”

Section: Introductionmentioning

confidence: 99%

Germline genetic contribution to the immune landscape of cancer

Sayaman

Saad

Thórsson

et al. 2020

Preprint

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SummaryThe role of germline genetics in shaping the tumor immune landscape is largely unknown. Using genotypes from >9,000 individuals in The Cancer Genome Atlas, we investigated the association of common and rare variants with 139 well-defined immune traits. Our analysis of common variants identified 10 immune traits with significant heritability estimates, and an additional 23 with suggestive heritability, including estimates of T-cell subset abundance and interferon signaling. We performed genome-wide association on the 33 heritable traits and identified 23 genome-wide significant loci associated with at least one immune trait, including SNPs in the IFIH1 locus previously associated with several autoimmune diseases. We also found significant associations between immune traits and pathogenic or likely-pathogenic rare variants in BRCA1 and in genes functionally linked to telomere stabilization, and Wnt/Beta-catenin signaling. We conclude that germline genetic variants significantly impact the composition and functional orientation of the tumor immune microenvironment.

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Transplant genetics and genomics

Cited by 64 publications

References 209 publications

Integrative omics for health and disease

Integrative omics for health and disease

Development and evaluation of a transfusion medicine genome wide genotyping array

Germline genetic contribution to the immune landscape of cancer

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