Combining cooperativity with sequestration: a novel strategy for discrimination of single nucleotide variants

2018 ◽  
Vol 54 (26) ◽  
pp. 3223-3226 ◽  
Author(s):  
Shichao Hu ◽  
Na Li ◽  
Feng Liu
Keyword(s):  
Single Nucleotide Variant ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Discrimination Ability ◽  
Novel Strategy

We present a novel single nucleotide variant discrimination strategy combining cooperativity with sequestration to significantly improve the discrimination ability.

Single nucleotide variant discrimination by toehold exchange spherical nucleic acids modulated on hierarchical molybdenum disulfide acanthospheres

2020 ◽  
Vol 56 (61) ◽  
pp. 8599-8602
Author(s):  
Min Zhu ◽  
Yanyan Yu ◽  
Junfeng Zhu ◽  
Yao Zhou ◽  
Gaoxing Su ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Molybdenum Disulfide ◽  
Sensitivity And Specificity ◽  
Single Nucleotide Variant ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Spherical Nucleic Acids

Toehold exchange spherical nucleic acids (TESNA) modulated on molybdenum disulfide acanthospheres are proposed for the discrimination of single nucleotide variants (SNVs) with significantly improved sensitivity and specificity.

scholarly journals Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B*15:02 and HLA-A*31:01 Across Diverse Ancestral Backgrounds

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda Buchner ◽  
Xiuying Hu ◽  
Katherine J. Aitchison
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Single Nucleotide Variant ◽  
Taqman Assay ◽  
Slight Reduction ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Leukocyte Antigen ◽  
Efficient Detection ◽  
Hla Haplotypes

The human leukocyte antigen haplotypes HLA-B*15:02 and HLA-A*31:01 have been linked to life-threatening adverse drug reactions to the anticonvulsants carbamazepine and oxcarbazepine. Identification of these haplotypes via pharmacogenetic techniques facilitates implementation of precision medicine to prevent such reactions. Using reference samples from diverse ancestral origins, we investigated the test analytical validity (i.e., ability to detect whether or not the haplotypes were present or absent) of TaqMan assays for single nucleotide variants previously identified as potentially being able to “tag” these haplotypes. A TaqMan custom assay for rs10484555 and an inventoried assay for rs17179220 and were able to identify with 100% sensitivity and 100% specificity HLA-B*15:02 and HLA-A*31:01 respectively. A custom assay for rs144012689 that takes into account a neighboring single nucleotide variant with manual calling was also able to identify HLA-B*15:02 with 100% sensitivity and 100% specificity. A custom assay for rs106235 identified HLA-A*31:01 with 100% sensitivity and 95% specificity. The slight reduction in specificity for the latter was owing to another haplotype (HLA-A*33:03) also being detected. While any positive call using the rs106235 assay could therefore be further investigated, as the presence of the HLA-A*31:01 haplotype confers adverse drug reaction risk, the absence of false negatives (indexed by sensitivity) is more important than false positives. In summary, we present validated TaqMan assay methodology for efficient detection of HLA haplotypes HLA-B*15:02 and HLA-A*31:01. Our data are relevant for other genotyping technologies that identify, or have the potential to identify, these haplotypes using single nucleotide variants.

scholarly journals A single nucleotide variant in the promoter region of the CCR5 gene increases susceptibility to arthritis encephalitis virus in goats

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Silvia Colussi ◽  
Rosanna Desiato ◽  
Chiara Beltramo ◽  
Simone Peletto ◽  
Paola Modesto ◽  
...  
Keyword(s):  
Promoter Region ◽  
Single Nucleotide Variant ◽  
Encephalitis Virus ◽  
Ccr5 Gene ◽  
Single Nucleotide

Single-Nucleotide Variants in microRNAs Sequences or in their Target Genes Might Influence the Risk of Epilepsy: A Review

2021 ◽  
Author(s):  
Renata Parissi Buainain ◽  
Matheus Negri Boschiero ◽  
Bruno Camporeze ◽  
Paulo Henrique Pires de Aguiar ◽  
Fernando Augusto Lima Marson ◽  
...  
Keyword(s):  
Target Genes ◽  
Single Nucleotide Variants ◽  
Single Nucleotide

scholarly journals Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Nayoung Han ◽  
Jung Mi Oh ◽  
In-Wha Kim
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Gain ◽  
Copy Number Variations ◽  
Gene Gain ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Control And Prevention

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

scholarly journals Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Hélène Morel ◽  
Olivier Milleron ◽  
Laurent Gouya ◽  
Christine Francannet ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Somatic Mosaicism ◽  
Variant Calling ◽  
Copy Number Variations ◽  
Pathogenic Variant ◽  
Single Nucleotide Variants ◽  
Bioinformatics Analyses ◽  
Single Nucleotide ◽  
Fbn1 Gene ◽  
Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

scholarly journals Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Fatao Liu ◽  
Yongsheng Li ◽  
Dongjian Ying ◽  
Shimei Qiu ◽  
Yong He ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Large Cell ◽  
Molecular Signatures ◽  
Single Nucleotide Variants ◽  
Oncogenic Signaling ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Deadly Disease ◽  
Oncogenic Signaling Pathways ◽  
Neuroendocrine Carcinomas

AbstractNeuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C > T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values = 0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease.

scholarly journals Missense RHD single nucleotide variants induce weakened D antigen expression by altering splicing and/or protein expression

Transfusion ◽  
2021 ◽  
Author(s):  
Loann Raud ◽  
Marlène Le Tertre ◽  
Léonie Vigneron ◽  
Chandran Ka ◽  
Gaëlle Richard ◽  
...  
Keyword(s):  
Protein Expression ◽  
Antigen Expression ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
D Antigen
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