The Phenolyzer Suite: Prioritizing the Candidate Genes Involved in Microtia

2019 ◽  
Vol 128 (6) ◽  
pp. 556-562 ◽  
Author(s):  
Huang Xin ◽  
Wang Changchen ◽  
Liu Lei ◽  
Yang Meirong ◽  
Zhang Ye ◽  
...  
Keyword(s):  
Candidate Genes ◽  
High Throughput ◽  
Potential Candidate ◽  
Single Nucleotide Variants ◽  
Gene Score ◽  
Single Nucleotide ◽  
Research Directions ◽  
Score System ◽  
Pathogenic Genes ◽  
First Time

Objective: Microtia is a congenital malformation of the external ear. Great progress about the genetic of microtia has been made in recent years. This article was to prioritize the potential candidate pathogenic genes of microtia based on existing studies and reports, with the purpose of narrowing the range of following study scientifically and quickly. Method: A computational tool called Phenolyzer (phenotype-based gene analyzer) was used to prioritize microtia genes. Microtia, as a query term, was input in the interface of Phenolyzer. After several steps, including disease match, gene query, gene score system, seed gene growth, and gene ranking, the final results about genetic information of microtia were provided. Then we tracked details of the top 10 genes ranked by Phenolyzer on the basis of previous reports. Results: We detected 10 348 genes associated with microtia or related syndromes, and 78 genes of those genes belonged to seed genes. Every gene was given a score, and the gene with higher scores was more likely influence microtia. The top 10 ranked genes included HOXA2, CHD7, CDT1, ORC1, ORC4, ORC6, CDC6, MED12, TWIST1, and GLI3. Otherwise, four gene-gene interactions were displayed. Conclusion: This article prioritized candidate genes of microtia for the first time. High-throughput methods provide tens of thousands of single-nucleotide variants, indels, and structural variants, and only a handful are relevant to microtia or associated syndromes. Combine the ranked potential pathogenic genes list from Phenolyzer with the results of samples provided by high-throughput methods, and more precise research directions are presented.

scholarly journals Pharmacokinetics and Pharmacogenetics of Apixaban

2020 ◽  
Vol 16 (5) ◽  
pp. 852-860
Author(s):  
A. V. Savinova ◽  
M. M. Petrova ◽  
N. A. Shnayder ◽  
E. N. Bochanova ◽  
R. F. Nasyrova
Keyword(s):  
Candidate Genes ◽  
Factor Xa ◽  
Potential Candidate ◽  
Beta Oxidation ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Genes Encoding ◽  
Deep Vein

Apixaban is oral anticoagulant, it is widely used in prevention of stroke in non-valvular atrial fibrillation and treatment of deep vein thrombosis and pulmonary embolism. Its main mechanism of action is through reversible inhibition of factor Xa. It specifically binds and inhibits both free and bound factor Xa which ultimately results in reduction in the levels of thrombin formation. Apixaban is mainly metabolized by CYP3A4 with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP2J2 isoenzymes. Some of the major metabolic pathways of apixaban include o-demethylation, hydroxylation, and sulfation, with o-demethylapixabansulphate being the major metabolite. The aim of this review is analysis of associated researches of single nucleotide variants (SNV) of CYP3A5 and SULT1A1 genes and search for new candidate genes reflecting effectiveness and safety of apixaban. The search for full-text publications in Russian and English languages containing key words “apixaban”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of apixaban are considered in this review. The hypothesis about CYP и SULT1A enzymes influence on apixaban metabolism was examined. To date, numerous SNVs of the CYP3A5 and SULT1A1 genes have been identified, but their potential influence on pharmacokinetics apixaban in clinical practice needs to be further studies. The role of SNVs of other genes encoding beta-oxidation enzymes of apixaban (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2J2) and transporter proteins (ABCB1, ABCG2) in its efficacy and safety are not well understood, and ABCB1 and ABCG2 genes may be potential candidate genes for studies of the drug safety.

scholarly journals Candidate genes associated with athletes' skeletal muscle functions regulation

2021 ◽  
Vol 1 (2) ◽  
pp. 83-94
Author(s):  
O. V. Balberova ◽  
E. V. Bykov ◽  
G. V. Medvedev
Keyword(s):  
Candidate Genes ◽  
Skeletal Muscles ◽  
Sports Injuries ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Genetic Characteristics ◽  
Endurance Strength ◽  
Personalized Approach ◽  
And Function ◽  
Genetically Determined

It is generally recognized that an elite athlete's status is a multifactorial phenotype depending on many environmental and genetic factors. Variations in the sequence of nucleotides in deoxyribonucleic acid (DNA), in particular, single-nucleotide variants (SNVs) act as key internal factors associated with achieving high results in sports. The determination of specific individuals' genetic characteristics allows us to identify athletes who have the greatest genetically determined potential for certain sports that require speed, strength or endurance manifestation. Of course, peculiarities of the structure and function of skeletal muscles are among the most important characteristics in sports results context, in sports associated with the development of power / strength or endurance phenotypes. The composition and function of skeletal muscles are controlled by many different genes, and their SNVs can serve as strength or endurance athletes' status biomarkers. (1) Background: to conduct a thematic review of candidate genes studies and their single-nucleotide variants (SNVs) associated with the functioning of skeletal muscles in athletes. (2) Methods: A search for articles for the period from 2010 to 2020 was conducted in the databases SCOPUS, Web of Science, Google Calendar, Clinical keys, PubMed, e-LIBRARY using keywords and their combinations; (3) Conclusions: The identification of genetic biomarkers associated with muscular system regulation can help neurologists, sports doctors and coaches in developing personalized strategies for selecting children, adolescents and young adults for endurance, strength and speed sports (for example, running short, medium or long distances). Such a personalized approach will increase sports performance and reduce the risk of sports injuries of the musculoskeletal system.

scholarly journals MethylExtract: High-Quality methylation maps and SNV calling from whole genome bisulfite sequencing data

F1000Research ◽  
2014 ◽  
Vol 2 ◽  
pp. 217 ◽  
Author(s):  
Guillermo Barturen ◽  
Antonio Rueda ◽  
José L. Oliver ◽  
Michael Hackenberg
Keyword(s):  
High Throughput ◽  
Sequence Variation ◽  
High Throughput Sequencing ◽  
Whole Genome ◽  
Single Nucleotide Variants ◽  
High Quality ◽  
Single Nucleotide ◽  
Error Sources ◽  
Link Type ◽  
Genome Methylation

Whole genome methylation profiling at a single cytosine resolution is now feasible due to the advent of high-throughput sequencing techniques together with bisulfite treatment of the DNA. To obtain the methylation value of each individual cytosine, the bisulfite-treated sequence reads are first aligned to a reference genome, and then the profiling of the methylation levels is done from the alignments. A huge effort has been made to quickly and correctly align the reads and many different algorithms and programs to do this have been created. However, the second step is just as crucial and non-trivial, but much less attention has been paid to the final inference of the methylation states. Important error sources do exist, such as sequencing errors, bisulfite failure, clonal reads, and single nucleotide variants.We developed MethylExtract, a user friendly tool to: i) generate high quality, whole genome methylation maps and ii) detect sequence variation within the same sample preparation. The program is implemented into a single script and takes into account all major error sources. MethylExtract detects variation (SNVs – Single Nucleotide Variants) in a similar way to VarScan, a very sensitive method extensively used in SNV and genotype calling based on non-bisulfite-treated reads. The usefulness of MethylExtract is shown by means of extensive benchmarking based on artificial bisulfite-treated reads and a comparison to a recently published method, called Bis-SNP.MethylExtract is able to detect SNVs within High-Throughput Sequencing experiments of bisulfite treated DNA at the same time as it generates high quality methylation maps. This simultaneous detection of DNA methylation and sequence variation is crucial for many downstream analyses, for example when deciphering the impact of SNVs on differential methylation. An exclusive feature of MethylExtract, in comparison with existing software, is the possibility to assess the bisulfite failure in a statistical way. The source code, tutorial and artificial bisulfite datasets are available at http://bioinfo2.ugr.es/MethylExtract/ and http://sourceforge.net/projects/methylextract/, and also permanently accessible from 10.5281/zenodo.7144.

Abstract 5173: Identification of single-nucleotide variants by high-throughput RNA sequencing in endemic Burkitt Lymphoma

2014 ◽  
Author(s):  
Maria Antonella Laginestra ◽  
Francesco Abate ◽  
Maryam Etebari ◽  
Giulia D. Falco ◽  
Fabio Fuligni ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
High Throughput ◽  
Burkitt Lymphoma ◽  
Single Nucleotide Variants ◽  
Single Nucleotide

scholarly journals Variants of Novel Immunomodulatory Fc Receptor Like 5 Gene Are Associated With Multiple Sclerosis Susceptibility in the Polish Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Monika Chorazy ◽  
Natalia Wawrusiewicz-Kurylonek ◽  
Edyta Adamska-Patruno ◽  
Agata Czarnowska ◽  
Olga Zajkowska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Polish Population ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Exact Test ◽  
Chi Squared ◽  
First Time

Fc receptors have been shown to play a role in several autoimmune diseases. We aimed to test, for the first time, whether some of the single nucleotide variants in the FCRL5 gene were associated with multiple sclerosis (MS) susceptibility and clinical manifestations in the Polish population. The case-control study included 94 individuals with MS and 160 healthy subjects. We genotyped two single nucleotide variants of the FCRL5 gene: rs2012199 and rs6679793. The age of onset, disease duration, and clinical condition of the MS subjects were analyzed. For statistical analysis, we used the chi-squared test confirmed with Fisher's exact test. We observed the significant differences in the distribution of investigated FCRL5 genotypes between MS subjects and healthy controls. The CC and CT genotypes, as well as the C allele of rs2012199, were significantly more common in the MS subjects, as were genotypes AA and AG, and allele A of rs6679793. We noted that decreased MS susceptibility was associated with the T allele rs2012199 (OR = 0.37, p = 0.0002) and G allele rs6679793 (OR = 0.6, p = 0.02). Our results support the role of the FCRL5 locus in MS predisposition and extend the evidence of its influence on autoimmunity.

scholarly journals Promising areas of research on the pharmacogenetics of dabigatran etexilate

2020 ◽  
pp. 35-41
Author(s):  
A. V. Savinova ◽  
N. A. Shnayder ◽  
M. M. Petrova ◽  
R. F. Nasyrova
Keyword(s):  
Candidate Genes ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
P Glycoprotein ◽  
Udp Glucuronosyltransferase

Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of promising areas of associated researches of SNV of genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.

Pharmacokinetics and Pharmacogenetics of Dabigatran

2021 ◽  
Vol 17 (1) ◽  
pp. 146-152
Author(s):  
A. V. Savinova ◽  
V. S. Dobrodeeva ◽  
M. M. Petrova ◽  
R. F. Nasyrova ◽  
N. A. Shnayder
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Potential Candidate ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
The Past ◽  
Potential Candidate Gene ◽  
P Glycoprotein ◽  
Udp Glucuronosyltransferase

Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.

scholarly journals Next generation sequencing analysis of patients with familial cervical artery dissection

2017 ◽  
Vol 2 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Caspar Grond-Ginsbach ◽  
Tobias Brandt ◽  
Manja Kloss ◽  
Suna Su Aksay ◽  
Philipp Lyrer ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Candidate Genes ◽  
Allele Frequency ◽  
Artery Dissection ◽  
Cervical Artery Dissection ◽  
Connective Tissue Disorders ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Cervical Artery ◽  
Stop Loss

Background The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. Patients and methods Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as “benign” or “likely benign” in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database ( n = 33,370). Results Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8–52.9). Conclusion Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

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