Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease

McCarroll, Steven A.; Bradner, James E.; Turpeinen, Hannu; Volin, Liisa; Martin, Paul J.; Chilewski, Shannon D; Antin, Joseph H.; Lee, Stephanie J.; Ruutu, Tapani; Storer, Barry E.; Warren, Edus H.; Zhang, Bo; Zhao, Lue Ping; Ginsburg, David; Soiffer, Robert J.; Partanen, Jukka; Hansen, John A.; Ritz, Jérôme; Palotie, Aarno; Altshuler, David

doi:10.1038/ng.490

Cited by 87 publications

(86 citation statements)

References 32 publications

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“…Besides these phase II metabolizing enzymes, several disease-associated genes were also found to overlap with these CNPs, such as the FCG receptor genes (autoimmune or inflammatory diseases), 30 TP63 31 and WWOX 26 (lung adenocarcinoma, gastric, pancreatic and other cancers), CFHR3 and CFHR1 (age-related macular degeneration), 32 UGT2B17 (prostate cancer and graft-versus-host disease), 33,34 Abbreviations: CNPs, copy number polymorphisms; UCSC, University of California Santa Cruz genes.…”

Section: Characteristics Of Cnps Identified By Canary (Birdsuite)mentioning

confidence: 99%

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A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Teo

Naidoo

et al. 2011

J Hum Genet

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The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population. We conducted a population-based study to detect and characterize CNVs and ROHs in 87 randomly selected healthy Swedish individuals using the Affymetrix SNP Array 6.0. More than 600 CNV loci were detected in the population using two different CNV-detection algorithms (PennCNV and Birdsuite). A total of 196 loci were consistently identified by both algorithms, suggesting their reliability. Numerous diseaseassociated and pharmacogenetics-related genes were found to be overlapping with common CNV loci such as CFHR1/R3, LCE3B/3C, UGT2B17 and GSTT1. Correlation analysis between copy number polymorphisms (CNPs) and genome-wide association studies-identified single-nucleotide polymorphisms also indicates the potential roles of several CNPs as causal variants for diseases and traits such as body mass index, Crohn's disease and multiple sclerosis. In addition, we also identified a total of 14 815 ROHs X500 kb or 2814 ROHs X1M in the Swedish individuals with an average of 170 and 32 regions detected per individual respectively. Approximately 141 Mb or 4.92% of the genome is homozygous in each individual of the Swedish population. This is the first population-based study to investigate the population characteristics of CNVs and ROHs in the Swedish population. This study found many CNV loci that warrant further investigation, and also highlighted the abundance and importance of investigating ROHs for their associations with complex diseases and traits.

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Section: Characteristics Of Cnps Identified By Canary (Birdsuite)mentioning

confidence: 99%

“…For example, the mismatch of the copy numbers of UGT2B17 was found to be associated with graft-versus-host disease in patients with hematopoietic stem cell transplantation. 34 Deletion of UGT2B17 was also associated with an increased risk for prostate cancer. 33 …”

Section: Characteristics Of Cnps Identified By Canary (Birdsuite)mentioning

confidence: 99%

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Teo

Naidoo

et al. 2011

J Hum Genet

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“…24 As mHAs were historically identified using biochemical means, state of the art genomic or proteomic screens may reveal the existence of many more mHAs. 25 Recent efforts using high-throughput genomics, in-silico prediction and candidate gene resequencing have already yielded some successes, 26 for example, in the recent discovery of histocompatibility genes that occur as a result of functional gene expression knockout by McCarroll et al 27 Such genes encode gene-expressed mismatch antigens (GEMAs), which are not expressed in a significant percentage of the human population due to the presence of two non-complementary null mutations at a single locus (Figure 2). In the context of transplantation, when donors and recipients are mismatched in the expression of a GEMA, GEMA-derived peptides are antigenic in the GEMA( À) individual.…”

Section: Application Of Sgs Technology To Gvhd Risk Assessment Beyondmentioning

confidence: 99%

Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation

Levine

Hákonarson

et al. 2013

Eur J Hum Genet

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Recent developments in second-generation sequencing (SGS) technologies provide an avenue for achieving rapid and accurate high-throughput analysis of human and microbial genomic diversity. SGS technologies have the potential to transform existing medical management of complex and life-threatening medical conditions by enabling clinicians to develop disease-targeted clinical care plans for each patient. In this review, we outline how innovative SGS-based approaches can improve the care of recipients of allogeneic hematopoietic cell transplantation (HCT), a life-saving procedure that carries a 1-year mortality risk of over 30%. We specifically evaluate foreseeable applications of SGS-based technology in facilitating rapid, phase-sensitive human leukocyte antigen (HLA) typing, assessment of non-HLA genomic compatibility, identifying patients at high risk for adverse drug reactions, and post-HCT monitoring for engraftment, minimal residual disease and infection. We conclude that innovative SGS approaches have the capacity to revolutionize the HCT recipient risk assessment process, support non-invasive clinical monitoring and improve patient outcomes, thereby setting the stage for a new era of genomically informed patient-centered medicine.

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“…The mismatch of UGT2B17 copy numbers in donors and recipients of stem cell transplantation were also associated with an increased risk of graftversus-host disease. 18 This gene is contained within CNP603, which Total deletion % Two-copy deletion % One-copy deletion % Total deletion % Two-copy deletion % One-copy deletion % Total deletion % Two-copy deletion % One-copy deletion % CNP874 deletion frequency CNP877 deletion frequency S i n g -I n d i a n…”

Section: Populationmentioning

confidence: 99%

Copy number polymorphisms in new HapMap III and Singapore populations

Teo

Naidoo

et al. 2011

J Hum Genet

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Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)o0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by in the 10 populations.

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Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease

Cited by 87 publications

References 32 publications

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation

Copy number polymorphisms in new HapMap III and Singapore populations

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