A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

Abstract The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species.

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Candidate gene studies in gallbladder cancer: A systematic review and meta-analysis

Mutation Research/Reviews in Mutation Research ◽

10.1016/j.mrrev.2011.06.002 ◽

2011 ◽

Vol 728 (1-2) ◽

pp. 67-79 ◽

Cited By ~ 60

Author(s):

Kshitij Srivastava ◽

Anvesha Srivastava ◽

Kiran Lata Sharma ◽

Balraj Mittal

Keyword(s):

Systematic Review ◽

Candidate Gene ◽

Gallbladder Cancer ◽

Meta Analysis ◽

Candidate Gene Studies

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Zebrafish Cancer Predisposition Models

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.660069 ◽

2021 ◽

Vol 9 ◽

Author(s):

Kim Kobar ◽

Keon Collett ◽

Sergey V. Prykhozhij ◽

Jason N. Berman

Keyword(s):

Large Scale ◽

Genetic Manipulation ◽

Bone Marrow Failure ◽

Cancer Predisposition ◽

Potential Candidate ◽

Cancer Evolution ◽

High Fecundity ◽

Cancer Models ◽

The Impact

Cancer predisposition syndromes are rare, typically monogenic disorders that result from germline mutations that increase the likelihood of developing cancer. Although these disorders are individually rare, resulting cancers collectively represent 5–10% of all malignancies. In addition to a greater incidence of cancer, affected individuals have an earlier tumor onset and are frequently subjected to long-term multi-modal cancer screening protocols for earlier detection and initiation of treatment. In vivo models are needed to better understand tumor-driving mechanisms, tailor patient screening approaches and develop targeted therapies to improve patient care and disease prognosis. The zebrafish (Danio rerio) has emerged as a robust model for cancer research due to its high fecundity, time- and cost-efficient genetic manipulation and real-time high-resolution imaging. Tumors developing in zebrafish cancer models are histologically and molecularly similar to their human counterparts, confirming the validity of these models. The zebrafish platform supports both large-scale random mutagenesis screens to identify potential candidate/modifier genes and recently optimized genome editing strategies. These techniques have greatly increased our ability to investigate the impact of certain mutations and how these lesions impact tumorigenesis and disease phenotype. These unique characteristics position the zebrafish as a powerful in vivo tool to model cancer predisposition syndromes and as such, several have already been created, including those recapitulating Li-Fraumeni syndrome, familial adenomatous polyposis, RASopathies, inherited bone marrow failure syndromes, and several other pathogenic mutations in cancer predisposition genes. In addition, the zebrafish platform supports medium- to high-throughput preclinical drug screening to identify compounds that may represent novel treatment paradigms or even prevent cancer evolution. This review will highlight and synthesize the findings from zebrafish cancer predisposition models created to date. We will discuss emerging trends in how these zebrafish cancer models can improve our understanding of the genetic mechanisms driving cancer predisposition and their potential to discover therapeutic and/or preventative compounds that change the natural history of disease for these vulnerable children, youth and adults.

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QTL detection and putative candidate gene prediction for leaf rolling under moisture stress condition in wheat

Scientific Reports ◽

10.1038/s41598-020-75703-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Aakriti Verma ◽

M. Niranjana ◽

S. K. Jha ◽

Niharika Mallick ◽

Priyanka Agarwal ◽

...

Keyword(s):

Drought Tolerance ◽

Candidate Gene ◽

Linkage Map ◽

Ssr Markers ◽

Stress Condition ◽

Recombinant Inbred Lines ◽

Snp Array ◽

Moisture Stress ◽

Potential Candidate ◽

Leaf Rolling

Abstract Leaf rolling is an important mechanism to mitigate the effects of moisture stress in several plant species. In the present study, a set of 92 wheat recombinant inbred lines derived from the cross between NI5439 × HD2012 were used to identify QTLs associated with leaf rolling under moisture stress condition. Linkage map was constructed using Axiom 35 K Breeder’s SNP Array and microsatellite (SSR) markers. A linkage map with 3661 markers comprising 3589 SNP and 72 SSR markers spanning 22,275.01 cM in length across 21 wheat chromosomes was constructed. QTL analysis for leaf rolling trait under moisture stress condition revealed 12 QTLs on chromosomes 1B, 2A, 2B, 2D, 3A, 4A, 4B, 5D, and 6B. A stable QTL Qlr.nhv-5D.2 was identified on 5D chromosome flanked by SNP marker interval AX-94892575–AX-95124447 (5D:338665301–5D:410952987). Genetic and physical map integration in the confidence intervals of Qlr.nhv-5D.2 revealed 14 putative candidate genes for drought tolerance which was narrowed down to six genes based on in-silico analysis. Comparative study of leaf rolling genes in rice viz., NRL1, OsZHD1, Roc5, and OsHB3 on wheat genome revealed five genes on chromosome 5D. Out of the identified genes, TraesCS5D02G253100 falls exactly in the QTL Qlr.nhv-5D.2 interval and showed 96.9% identity with OsZHD1. Two genes similar to OsHB3 viz. TraesCS5D02G052300 and TraesCS5D02G385300 exhibiting 85.6% and 91.8% identity; one gene TraesCS5D02G320600 having 83.9% identity with Roc5 gene; and one gene TraesCS5D02G102600 showing 100% identity with NRL1 gene were also identified, however, these genes are located outside Qlr.nhv-5D.2 interval. Hence, TraesCS5D02G253100 could be the best potential candidate gene for leaf rolling and can be utilized for improving drought tolerance in wheat.

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Candidate Gene Selection for Cytoplasmic Male Sterility in Pepper (Capsicum annuum L.) through Whole Mitochondrial Genome Sequencing

International Journal of Molecular Sciences ◽

10.3390/ijms20030578 ◽

2019 ◽

Vol 20 (3) ◽

pp. 578 ◽

Cited By ~ 9

Author(s):

Peng Wang ◽

Qiaohua Lu ◽

Yixin Ai ◽

Yihao Wang ◽

Tiantian Li ◽

...

Keyword(s):

Mitochondrial Genome ◽

Cytoplasmic Male Sterility ◽

Candidate Gene ◽

Male Sterility ◽

Gene Selection ◽

Transmembrane Domain ◽

Genome Structure ◽

Potential Candidate ◽

Hybrid Seed Production ◽

Cms Line

Cytoplasmic male sterility (CMS), which is controlled by mitochondrial genes, is an important trait for commercial hybrid seed production. So far, genes controlling this trait are still not clear in pepper. In this study, complete mitochondrial genomes were sequenced and assembled for the CMS line 138A and its maintainer line 138B. The genome size of 138A is 504,210 bp, which is 8618 bp shorter than that of 138B. Meanwhile, more than 214 and 215 open reading frames longer than 100 amino acids (aas) were identified in 138A and 138B, respectively. Mitochondrial genome structure of 138A was quite different from that of 138B, indicating the existence of recombination and rearrangement events. Based on the mitochondrial genome sequence and structure variations, mitochondrion of 138A and FS4401, a Korean origin CMS line, may have inherited from a common female ancestor, but their CMS traits did originate separately. Candidate gene selection was performed according to the published characteristics of the CMS genes, including the presence SNPs and InDels, located in unique regions, their chimeric structure, co-transcription, and transmembrane domain. A total of 35 ORFs were considered as potential candidate genes and 14 of these were selected, with orf300a and 0rf314a as strong candidates. A new marker, orf300a, was developed which did co-segregate with the CMS trait.

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BRIP1 a potential candidate gene in development of non-BRCA1 2 breast cancer

Frontiers in Bioscience ◽

10.2741/767 ◽

2016 ◽

Vol 8 (2) ◽

pp. 289-298

Author(s):

Allal Ouhtit

Keyword(s):

Breast Cancer ◽

Candidate Gene ◽

Potential Candidate ◽

Potential Candidate Gene

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Association of DNA repair and cell cycle gene variations with breast cancer risk in Northeast Indian population: a multiple interaction analysis

Tumor Biology ◽

10.1007/s13277-014-1779-2 ◽

2014 ◽

Vol 35 (6) ◽

pp. 5885-5894 ◽

Cited By ~ 12

Author(s):

Mishi Kaushal Wasson ◽

Pradeep Singh Chauhan ◽

L. C. Singh ◽

Dheeraj Katara ◽

Jagannath Dev Sharma ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Dna Repair ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Indian Population ◽

Interaction Analysis ◽

Cell Cycle Gene ◽

Multiple Interaction

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Global Characterization of Metabolic Genes Regulating Survival and Immune Infiltration in Osteosarcoma

Frontiers in Genetics ◽

10.3389/fgene.2021.814843 ◽

2022 ◽

Vol 12 ◽

Author(s):

Zhongpei Zhu ◽

Min Zhang ◽

Weidong Wang ◽

Peng Zhang ◽

Yuqiang Wang ◽

...

Keyword(s):

Tumor Microenvironment ◽

Candidate Gene ◽

Cell Lines ◽

Immune Cells ◽

Immune Cell ◽

Computational Techniques ◽

Potential Candidate ◽

Osteosarcoma Cell ◽

Potential Candidate Gene ◽

Metabolic Genes

Background: The alterations in metabolic profile of tumors have been identified as one of the prognostic hallmarks of cancers, including osteosarcoma. These alterations are majorly controlled by groups of metabolically active genes. However, the regulation of metabolic gene signatures in tumor microenvironment of osteosarcoma has not been well explained.Objectives: Thus, we investigated the sets of previously published metabolic genes in osteosarcoma patients and normal samples.Methods: We applied computational techniques to identify metabolic genes involved in the immune function of tumor microenvironment (TME) and survival and prognosis of the osteosarcoma patients. Potential candidate gene PAICS (phosphoribosyl aminoimidazole carboxylase, phosphoribosyl aminoimidazole succino carboxamide synthetase) was chosen for further studies in osteosarcoma cell lines for its role in cell proliferation, migration and apoptosis.Results: Our analyses identified a list of metabolic genes differentially expressed in osteosarcoma tissues. Next, we scrutinized the list of genes correlated with survival and immune cells, followed by clustering osteosarcoma patients into three categories: C1, C2, and C3. These analyses led us to choose PAICS as potential candidate gene as its expression showed association with poor survival and negative correlation with the immune cells. Furthermore, we established that loss of PAICS induced apoptosis and inhibited proliferation, migration, and wound healing in HOS and MG-63 cell lines. Finally, the results were supported by constructing and validating a prediction model for prognosis of the osteosarcoma patients.Conclusion: Here, we conclude that metabolic genes specifically PAICS play an integral role in the immune cell infiltration in osteosarcoma TME, as well as cancer development and metastasis.

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Identification of Potential Mpro Inhibitors for the Treatment of COVID-19 by Targeted Covalent Inhibition

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.20210401.oa1 ◽

2021 ◽

Vol 6 (2) ◽

pp. 1-20

Author(s):

Dushyant V. Patel ◽

Divya M. Teli ◽

Ashish M. Kanhed ◽

Nirav R. Patel ◽

Bhavik S. Shah ◽

...

Keyword(s):

Interaction Analysis ◽

Covalent Binding ◽

Receptor Interaction ◽

Potential Candidate ◽

Structural Protein ◽

Michael Adduct ◽

Curcumin Derivatives ◽

Novel Coronavirus ◽

Catalytic Dyad ◽

Virtual Screening Approach

A novel coronavirus is the causative agent identified for the current COVID-19 outbreak. Globally, more than 43 million people have been infected by this virus. The total number of deaths has surpassed 1.6 million across 210 countries due to the current pandemic. Till date, there is no specific therapeutic agent available for its treatment. Mpro, a non-structural protein cleaves viral polyproteins into other non-structural proteins. Inhibition of Mpro could prevent the virus replication projecting it as a potential candidate for anti-COVID-19 drug development. The authors report herein 10 top-ranked curcumin derivatives as non-peptide covalent-binding Mpro inhibitors using systematic virtual screening approach. Detailed ligand-receptor interaction analysis conferred that the α,β-unsaturated carbonyl moiety of curcumin functions as a warhead to yield a Michael adduct with Cys145 of the catalytic dyad of Mpro. Collectively, these results have offered new high affinity molecules for the development of potential drugs for the treatment of COVID-19.

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