Next-Generation Sequencing and Genotype Association Studies Reveal the Association of HLA-DRB3*02:02 With Delayed Hypersensitivity to Penicillins

Background: Nonimmediate (delayed) allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods: Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; P <0.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA-DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; P=0.001), but not immediate hypersensitivity. Conclusion: We showed that the HLA-DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA-DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.

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Analysis and Optimal Design for Association Studies Using Next-Generation Sequencing With Case-Control Pools

Genetic Epidemiology ◽

10.1002/gepi.21681 ◽

2012 ◽

pp. n/a-n/a

Author(s):

Wei E. Liang ◽

Duncan C. Thomas ◽

David V. Conti

Keyword(s):

Next Generation Sequencing ◽

Optimal Design ◽

Association Studies ◽

Case Control ◽

Next Generation ◽

Generation Sequencing

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Design and validation of a next generation sequencing assay for hereditaryBRCA1andBRCA2mutation testing

PeerJ ◽

10.7717/peerj.2162 ◽

2016 ◽

Vol 4 ◽

pp. e2162 ◽

Cited By ~ 13

Author(s):

Hyunseok P. Kang ◽

Jared R. Maguire ◽

Clement S. Chu ◽

Imran S. Haque ◽

Henry Lai ◽

...

Keyword(s):

Next Generation Sequencing ◽

Copy Number Variants ◽

Next Generation ◽

Single Nucleotide Variants ◽

Cancer Syndrome ◽

Cancer Screen ◽

Inherited Cancer ◽

Increased Risk ◽

Large Rearrangements ◽

Generation Sequencing

Hereditary breast and ovarian cancer syndrome, caused by a germline pathogenic variant in theBRCA1orBRCA2(BRCA1/2) genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have aBRCA1/2mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited Cancer Screen, a next-generation-sequencing-based test to detect pathogenic variation in theBRCA1andBRCA2genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy-number variants (CNVs, also known as large rearrangements) with zero errors over a 114-sample validation set consisting of samples from cell lines and deidentified patient samples, including 36 samples withBRCA1/2pathogenic germline mutations.

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Genetic Association Studies and Next Generation Sequencing in Stroke: Methods

Stroke Genetics ◽

10.1007/978-3-319-56210-0_3 ◽

2017 ◽

pp. 21-52

Author(s):

Jane M. Maguire ◽

Elizabeth G. Holliday ◽

Christopher J. Oldmeadow ◽

John Attia ◽

Matthew P. A. Henderson ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies ◽

Next Generation ◽

Generation Sequencing

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Use of Linkage Analysis, Genome-Wide Association Studies, and Next-Generation Sequencing in the Identification of Disease-Causing Mutations

Methods in Molecular Biology - Pharmacogenomics ◽

10.1007/978-1-62703-435-7_8 ◽

2013 ◽

pp. 127-146 ◽

Cited By ~ 10

Author(s):

Eric Londin ◽

Priyanka Yadav ◽

Saul Surrey ◽

Larry J. Kricka ◽

Paolo Fortina

Keyword(s):

Next Generation Sequencing ◽

Linkage Analysis ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Next Generation ◽

Genome Wide ◽

Generation Sequencing

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Association studies for next-generation sequencing

Genome Research ◽

10.1101/gr.115998.110 ◽

2011 ◽

Vol 21 (7) ◽

pp. 1099-1108 ◽

Cited By ~ 66

Author(s):

L. Luo ◽

E. Boerwinkle ◽

M. Xiong

Keyword(s):

Next Generation Sequencing ◽

Association Studies ◽

Next Generation ◽

Generation Sequencing

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Genetic and epigenetic characterization of the cry1Ab coding region and its 3′ flanking genomic region in MON810 maize using next-generation sequencing

European Food Research and Technology ◽

10.1007/s00217-018-3062-z ◽

2018 ◽

Vol 244 (8) ◽

pp. 1473-1485 ◽

Cited By ~ 1

Author(s):

Sina-Elisabeth Ben Ali ◽

Alexandra Schamann ◽

Stefanie Dobrovolny ◽

Alexander Indra ◽

Sarah Zanon Agapito-Tenfen ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genomic Region ◽

Next Generation ◽

Coding Region ◽

Generation Sequencing ◽

Mon810 Maize

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Complex genetics of pulmonary diseases: lessons from genome-wide association studies and next-generation sequencing

Translational Research ◽

10.1016/j.trsl.2015.04.016 ◽

2016 ◽

Vol 168 ◽

pp. 22-39 ◽

Cited By ~ 7

Author(s):

Nima Pouladi ◽

Christian Bime ◽

Joe G.N. Garcia ◽

Yves A. Lussier

Keyword(s):

Next Generation Sequencing ◽

Association Studies ◽

Genome Wide Association ◽

Pulmonary Diseases ◽

Genome Wide Association Studies ◽

Next Generation ◽

Complex Genetics ◽

Genome Wide ◽

Generation Sequencing

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Data mining of post genome-wide association studies and next generation sequencing

10.5353/th_b5106519 ◽

2013 ◽

Author(s):

Hongsheng Gui

Keyword(s):

Data Mining ◽

Next Generation Sequencing ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Next Generation ◽

Genome Wide ◽

Generation Sequencing

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Design and validation of a next generation sequencing assay for hereditary breast and ovarian cancer

10.7287/peerj.preprints.1463v1 ◽

2015 ◽

Author(s):

Hyunseok P. Kang ◽

Jared R Maguire ◽

Clement S Chu ◽

Imran S. Haque ◽

Henry Lai ◽

...

Keyword(s):

Ovarian Cancer ◽

Next Generation Sequencing ◽

Next Generation ◽

Single Nucleotide Variants ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Cancer Screen ◽

Inherited Cancer ◽

Increased Risk ◽

Generation Sequencing

Hereditary breast and ovarian cancer syndrome, caused by a germline deleterious variant in the BRCA1 or BRCA2 genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have a BRCA1/2 mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited Cancer Screen, a next-generation-sequencing-based test to detect pathogenic variation in the BRCA1 and BRCA2 genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy-number variants (CNVs, also known as large rearrangements) with zero errors over a 96-sample validation set consisting of samples from cell lines and deidentified patient samples, including the well-characterized NA12878 sample from HapMap/1000 Genomes.

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