scholarly journals Discrepancies between human DNA, mRNA and protein reference sequences and their relation to single nucleotide variants in the human population

Database ◽  
2016 ◽  
Vol 2016 ◽  
pp. baw124 ◽  
Author(s):  
Matsuyuki Shirota ◽  
Kengo Kinoshita
Keyword(s):  
Human Population ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Human Dna ◽  
Reference Sequences

scholarly journals The integrity of the U12 snRNA 3′ stem–loop is necessary for its overall stability

2021 ◽  
Vol 49 (5) ◽  
pp. 2835-2847
Author(s):  
Antto J Norppa ◽  
Mikko J Frilander
Keyword(s):  
Steady State ◽  
Early Onset ◽  
Human Population ◽  
Genetic Diseases ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Stem Loop ◽  
Snrna Gene ◽  
Small Nuclear Rnas ◽  
Overall Stability

Abstract Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C>U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C>T mutation in the U12 snRNA gene (RNU12). We show that the 84C>U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3′-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C>U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3′-to-5′ exonuclease. Finally, we show that several other single-nucleotide variants in the 3′ stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3′ stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.

scholarly journals Human DNA AI Model to Predict COVID-19 Symptomatic or Asymptomatic Percentages

2021 ◽  
Author(s):  
Peter Oropeza Martinez ◽  
Haydeé Rosas-Vargas ◽  
Luis Gaggero-Sager
Keyword(s):  
Neural Networks ◽  
Human Genome ◽  
Convolutional Neural Networks ◽  
Online Survey ◽  
Deoxyribonucleic Acid ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Image Structure ◽  
Human Dna ◽  
Nuclear Deoxyribonucleic Acid

Abstract The current paper proposes to use convolutional neural networks (CNN) to analyze human genome single nucleotide variants (SNVs) from nuclear deoxyribonucleic acid (DNA) and mitochondrial deoxyribonucleic acid (mtDNA) presented as a 2D image structure to understand if the answer to COVID-19 severities can be found in the human genome. That methodology was implemented with 447 Mexican population samples. From the results, two main groups were formed divided into symptomatic and asymptomatic cases composed of 80.986% and 19.014% respectively and the model was validated through an online survey of individuals, giving a 91.89% of accuracy.

scholarly journals Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population

GigaScience ◽  
2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Jeffrey B S Gaither ◽  
Grant E Lammi ◽  
James L Li ◽  
David M Gordon ◽  
Harkness C Kuck ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Human Population ◽  
Large Scale ◽  
Rna Folding ◽  
Rna Stability ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Human Transcriptome ◽  
Mrna Structure ◽  
The Impact

Abstract Background The role of synonymous single-nucleotide variants in human health and disease is poorly understood, yet evidence suggests that this class of “silent” genetic variation plays multiple regulatory roles in both transcription and translation. One mechanism by which synonymous codons direct and modulate the translational process is through alteration of the elaborate structure formed by single-stranded mRNA molecules. While tools to computationally predict the effect of non-synonymous variants on protein structure are plentiful, analogous tools to systematically assess how synonymous variants might disrupt mRNA structure are lacking. Results We developed novel software using a parallel processing framework for large-scale generation of secondary RNA structures and folding statistics for the transcriptome of any species. Focusing our analysis on the human transcriptome, we calculated 5 billion RNA-folding statistics for 469 million single-nucleotide variants in 45,800 transcripts. By considering the impact of all possible synonymous variants globally, we discover that synonymous variants predicted to disrupt mRNA structure have significantly lower rates of incidence in the human population. Conclusions These findings support the hypothesis that synonymous variants may play a role in genetic disorders due to their effects on mRNA structure. To evaluate the potential pathogenic impact of synonymous variants, we provide RNA stability, edge distance, and diversity metrics for every nucleotide in the human transcriptome and introduce a “Structural Predictivity Index” (SPI) to quantify structural constraint operating on any synonymous variant. Because no single RNA-folding metric can capture the diversity of mechanisms by which a variant could alter secondary mRNA structure, we generated a SUmmarized RNA Folding (SURF) metric to provide a single measurement to predict the impact of secondary structure altering variants in human genetic studies.

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

scholarly journals scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gavin W. Wilson ◽  
Mathieu Derouet ◽  
Gail E. Darling ◽  
Jonathan C. Yeung
Keyword(s):  
Genetic Variants ◽  
False Positive ◽  
Variant Calling ◽  
Call Rate ◽  
Rna Seq ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Variant Call ◽  
Two Samples ◽  
Co Detection

AbstractIdentifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to “collapse” molecular duplicates and accurately identify variants and their co-expression. We demonstrate that scSNV is fast, with a reduced false-positive variant call rate, and enables the co-detection of genetic variants and A>G RNA edits across twenty-two samples.

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