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Genomics review

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https://www.readbyqxmd.com/read/29913353/leveraging-gwas-for-complex-traits-to-detect-signatures-of-natural-selection-in-humans
#1
REVIEW
Jing Guo, Jian Yang, Peter M Visscher
Natural selection can shape the genetic architecture of complex traits. In human populations, signals of positive selection at genetic loci have been detected through a variety of genome-wide scanning approaches without the knowledge of how genes affect traits or fitness. In the past decade, genome-wide association studies (GWAS) have provided unprecedented insights into the genetic basis of quantitative variation in complex traits. Summary statistics generated from these GWAS have been shown to be an extraordinary data source that can be utilized to detect and quantify natural selection in the genetic architecture of complex traits...
June 15, 2018: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29913211/nrf2-molecular-and-epigenetic-regulation-during-aging
#2
REVIEW
A Silva-Palacios, M Ostolga-Chavarría, C Zazueta, M Königsberg
Increase in life-span is commonly related with age-related diseases and with gradual loss of genomic, proteomic and metabolic integrity. Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) controls the expression of genes whose products include antioxidant proteins, detoxifying enzymes, drug transporters and numerous cytoprotective proteins. Several experimental approaches have evaluated the potential regulation of the transcription factor Nrf2 to enhance the expression of genes that contend against accumulative oxidative stress and promote healthy aging...
June 15, 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29913185/pleiotropic-roles-of-the-ubiquitin-proteasome-system-during-viral-propagation
#3
REVIEW
Qi Tang, Peng Wu, Huiqing Chen, Guohui Li
Protein ubiquitination is a highly conserved post-translational modification affecting various biological processes including viral propagation. Ubiquitination has multiple effects on viral propagation, including viral genome uncoating, viral replication, and immune evasion. Ubiquitination of viral proteins is triggered by the ubiquitin-proteasome system (UPS). This involves the covalent attachment of the highly conserved 76 amino acid residue ubiquitin protein to target proteins by the consecutive actions of E1, E2 and E3 enzymes, and the 26S proteasome that together form a multiprotein complex that degrades target proteins...
June 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29913182/the-genetic-architecture-of-type-1-diabetes-mellitus
#4
REVIEW
Denis M Nyaga, Mark H Vickers, Craig Jefferies, Jo K Perry, Justin M O'Sullivan
Type 1 diabetes mellitus (T1D) is a complex autoimmune disorder characterised by loss of the insulin-producing pancreatic beta cells in genetically predisposed individuals, ultimately resulting in insulin deficiency and hyperglycaemia. T1D is most common among children and young adults, and the incidence is on the rise across the world. The aetiology of T1D is hypothesized to involve genetic and environmental factors that result in the T-cell mediated destruction of pancreatic beta cells. There is a strong genetic risk to T1D; with genome-wide association studies (GWAS) identifying over 60 susceptibility regions within the human genome which are marked by single nucleotide polymorphisms (SNPs)...
June 15, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29912596/understanding-resistance-mechanisms-to-btk-and-bcl2-inhibitors-in-mantle-cell-lymphoma-implications-for-design-of-clinical-trials
#5
Rishu Agarwal, Mark A Dawson, Martin Dreyling, Constantine S Tam
Novel targeted therapeutics has significantly improved the outlook of patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Despite significant efficacy, one of the major limitations of these targeted agents is presence of primary or acquired resistance to these novel drugs. Patients who fail primary therapy especially with ibrutinib have poor outcomes and may respond poorly to subsequent therapies. Hence, it is important to understand resistance mechanisms a priori to identify patients who are unlikely to respond, and to explore alternative therapeutic strategies...
June 18, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29912582/biomarkers-of-aggressiveness-in-genitourinary-tumors-with-emphasis-on-kidney-bladder-and-prostate-cancer
#6
Alessia Cimadamore, Silvia Gasparrini, Matteo Santoni, Liang Cheng, Antonio Lopez-Beltran, Nicola Battelli, Francesco Massari, Francesca Giunchi, Michelangelo Fiorentino, Marina Scarpelli, Rodolfo Montironi
Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas covered: Protein expression levels in immunohistochemistry and molecular biomarkers are reported for their ability to predict recurrence, progression, development of metastases, or patient survival. In particular, for renal cell carcinoma, we take into consideration the biomarkers applicable to immunohistochemistry and with molecular and genetic analyses...
June 18, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29912402/cutting-edge-genetics-crispr-cas9-editing-of-plant-genomes
#7
Cara L Soyars, Brenda A Peterson, Christian A Burr, Zachary L Nimchuk
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) system is a genome editing technology transforming the field of plant biology by virtue of the system's efficiency and specificity. The system has quickly evolved for many diverse applications including multiplex gene mutation, gene replacement, and transcriptional control. As CRISPR/Cas9 is increasingly applied to plants, it is becoming clear that each component of the system can be modified to improve editing results...
April 18, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29912321/genome-wide-studies-of-heart-failure-and-endophenotypes-lessons-learned-and-future-directions
#8
M Yldau van der Ende, M Abdullah Said, Dirk J van Veldhuisen, N Verweij, Pim van der Harst
Heart failure (HF) is a complex clinical syndrome resulting from structural or functional impairments of ventricular filling or ejection of blood. HF has a poor prognosis and the burden to society remains tremendous. The unfulfilled expectation is that expanding our knowledge of the genetic architecture of HF will help to quickly advance the quality of risk assessment, diagnoses, and treatment. To date, Genome Wide Association Studies (GWAS) of HF have led to disappointing results with only limited progress in our understanding and tempering the earlier expectations...
April 18, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29912293/crispr-cas9-in-plants-at-play-in-the-genome-and-at-work-for-crop-improvement
#9
Babar Hussain, Stuart James Lucas, Hikmet Budak
The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system uses single-guide RNAs for genome editing, making it a simple, robust, powerful tool for targeted gene mutagenesis, knockout and knock-in/replacement, as well as transcriptional regulation. Here, we review the working principles, components and potential modifications of CRISPR/Cas9 for efficient single and multiplex gene editing in plants. We also describe recent work that has used CRISPR/Cas9 to improve economically important traits in crop plants...
April 17, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29911261/the-interplay-between-oxytocin-and-the-crf-system-regulation-of-the-stress-response
#10
Julia Winter, Ben Jurek
Oxytocin (OT) has drawn the attention of researchers since 1930. Since then, many aspects of oxytocin have been uncovered, such as reproductive functions, dampening anxiety, enhancing socioemotional behavior, or regulating genomic effects on a cellular level. Here, we want to focus on the interaction between the OT system and the stress/corticotropin-releasing factor (CRF)-system of the brain. Depending on the nature of the stressor, OT is released simultaneously or directly after the stress from the neurohypophysis into the periphery and/or via somato-dendritic release in stress-sensitive brain areas...
June 18, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29911109/prostate-cancer-in-the-era-of-omic-medicine-recognizing-the-importance-of-dna-damage-repair-pathways
#11
REVIEW
Zachary Kornberg, Jonathan Chou, Felix Y Feng, Charles J Ryan
Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911108/emerging-application-of-genomics-guided-therapeutics-in-personalized-lung-cancer-treatment
#12
REVIEW
Aubhishek Zaman, Trever G Bivona
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911107/colorectal-cancer-genomics-and-designing-rational-trials
#13
REVIEW
Sebastian Mondaca, Rona Yaeger
The widespread use of next generation sequencing (NGS) has led to a refined understanding of the genomics of colorectal cancer (CRC). However, progress in the use of molecular biomarkers in standard practice has been slow, and there is no approved targeted therapy for CRC based on a positive predictive marker yet. In this review, we will first summarize biomarkers with clinical utility in standard practice or targeted therapy trials and then consider how to rationally design clinical trials to more effectively target CRC...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911105/genetics-of-cardiovascular-disease-fishing-for-causality
#14
REVIEW
Christoph Paone, Federica Diofano, Deung-Dae Park, Wolfgang Rottbauer, Steffen Just
Cardiovascular disease (CVD) is still the leading cause of death in all western world countries and genetic predisposition in combination with traditional risk factors frequently mediates their manifestation. Genome-wide association (GWA) studies revealed numerous potentially disease modifying genetic loci often including several SNPs and associated genes. However, pure genetic association does not prove direct or indirect relevance of the modifier region on pathogenesis, nor does it define within the associated region the exact genetic driver of the disease...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29910779/survival-and-energy-producing-strategies-of-alkane-degraders-under-extreme-conditions-and-their-biotechnological-potential
#15
REVIEW
Chulwoo Park, Woojun Park
Many petroleum-polluted areas are considered as extreme environments because of co-occurrence of low and high temperatures, high salt, and acidic and anaerobic conditions. Alkanes, which are major constituents of crude oils, can be degraded under extreme conditions, both aerobically and anaerobically by bacteria and archaea of different phyla. Alkane degraders possess exclusive metabolic pathways and survival strategies, which involve the use of protein and RNA chaperones, compatible solutes, biosurfactants, and exopolysaccharide production for self-protection during harsh environmental conditions such as oxidative and osmotic stress, and ionic nutrient-shortage...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29910775/variability-of-bacterial-essential-genes-among-closely-related-bacteria-the-case-of-escherichia-coli
#16
REVIEW
Enrique Martínez-Carranza, Hugo Barajas, Luis-David Alcaraz, Luis Servín-González, Gabriel-Yaxal Ponce-Soto, Gloria Soberón-Chávez
The definition of bacterial essential genes has been widely pursued using different approaches. Their study has impacted several fields of research such as synthetic biology, the construction of bacteria with minimal chromosomes, the search for new antibiotic targets, or the design of strains with biotechnological applications. Bacterial genomes are mosaics that only share a small subset of gene-sequences (core genome) even among members of the same species. It has been reported that the presence of essential genes is highly variable between closely related bacteria and even among members of the same species, due to the phenomenon known as "non-orthologous gene displacement" that refers to the coding for an essential function by genes with no sequence homology due to horizontal gene transfer (HGT)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29910655/clinical-application-and-utility-of-genomic-assays-in-early-stage-breast-cancer-key-lessons-learned-to-date
#17
REVIEW
S K L Chia
Early-stage hormone receptor-positive breast cancer is the most common subtype and stage presenting in countries with organized screening programs. Standard clinical and pathologic factors are routinely used to support prognosis and decisions about adjuvant therapies. Hormone receptor and her2 status are essential for decision-making about the use of adjuvant hormonal and anti-her2 therapies respectively. Genomic assays are now commercially available to aid in either further prognostication or in refining the potential benefit of adjuvant chemotherapy...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29910006/toward-a-variable-rbe-for-proton-beam-therapy
#18
REVIEW
Henning Willers, Antino Allen, David Grosshans, Stephen J McMahon, Cläre von Neubeck, Claudia Wiese, Bhadrasain Vikram
In the clinic, proton beam therapy (PBT) is based on the use of a generic relative biological effectiveness (RBE) of 1.1 compared to photons in human cancers and normal tissues. However, the experimental basis for this RBE lacks any significant number of representative tumor models and clinically relevant endpoints for dose-limiting organs at risk. It is now increasingly appreciated that much of the variations of treatment responses in cancers are due to inter-tumoral genomic heterogeneity. Indeed, recently it has been shown that defects in certain DNA repair pathways, which are found in subsets of many cancers, are associated with a RBE increase in vitro...
June 14, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29909570/functions-and-impact-of-tal-like-genes-in-animals-with-regard-to-applied-aspects
#19
REVIEW
Min Zhu, Xiaolong Hu, Guangli Cao, Renyu Xue, Chengliang Gong
A large number of DNAs in eukaryote genomes can code for atypical transcripts, and their functions are controversial. It has been reported that the transcripts contain many small open reading frames (sORFs), which were originally considered as non-translatable RNAs. However, increasing evidence has suggested that some of these sORFs can encode for small peptides and some are conserved across large evolutionary distances. It has been reported that the small peptides have functions and may be involved in varieties of cellular processes, playing important roles in development, physiology, and metabolism...
June 16, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29909134/the-influence-of-the-intestinal-microbiome-on-vaccine-responses
#20
REVIEW
Petra Zimmermann, Nigel Curtis
There is substantial variation between individuals in the immune response to vaccinations. The intestinal microbiome plays a crucial rule in the development and regulation of the immune system and therefore its composition might affect how individuals respond to vaccinations. In this review, we summarise studies that investigated the influence of the intestinal microbiome on humoral and cellular vaccine responses. To date, only four studies (three in infants and one in adults) have investigated the influence of the intestinal microbiome on vaccine responses...
June 13, 2018: Vaccine
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