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Current Opinion in Genetics & Development | Page 2

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https://read.qxmd.com/read/31102978/biology-of-multiciliated-cells
#21
REVIEW
Camille Boutin, Laurent Kodjabachian
Multiciliated cells (MCCs) are specialized in fluid propulsion through directional beating of myriads of superficial motile cilia, which rest on modified centrioles named basal bodies. MCCs are found throughout metazoans, and serve functions as diverse as feeding and locomotion in marine organisms, as well as mucus clearance, cerebrospinal fluid circulation, and egg transportation in mammals. Impaired MCC differentiation or activity causes diseases characterized by severe chronic airway infections and reduced fertility...
May 15, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31078084/deciphering-the-universe-of-genetic-context-dependencies-using-mouse-models-of-cancer
#22
REVIEW
Chiara Falcomatà, Stefanie Bärthel, Günter Schneider, Dieter Saur, Christian Veltkamp
Molecular profiling of cancer patients and modelling of human cancer in mice revealed cell type and tissue-specific differences in tumor development and evolution. However, the context-dependent determinants of cancer remain poorly understood. A systematic characterization of the biological underpinnings of context-specificity will, therefore, be pivotal to design more effective therapies. In this review article, we focus on recent advances on molecular, cellular and microenvironmental aspects of context-dependency...
May 8, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31078083/engineering-crispr-mouse-models-of-cancer
#23
REVIEW
Julia Weber, Roland Rad
Gene targeting in mammals has revolutionized the study of complex diseases, involving the interaction of multiple genes, cells, and organ systems. In cancer, genetically engineered mouse models deciphered biological principles by integrating molecular mechanisms, cellular processes, and environmental signals. Major advances in manipulative mouse genetics are currently emerging from breakthroughs in gene editing, which open new avenues for rapid model generation. Here, we review recent developments in engineering CRISPR mouse models of cancer...
May 8, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31063922/genome-scale-drop-out-screens-to-identify-cancer-cell-vulnerabilities-in-aml
#24
REVIEW
Faisal T Basheer, George S Vassiliou
Acute myeloid leukemia (AML) is an aggressive cancer that remains lethal to the majority of sufferers. Whilst the mainstay treatments for this condition have remained largely unchanged over the past five decades, progress in deciphering its pathogenesis has accelerated in recent years, propelled in part by advances in cancer genomics and mechanistic studies of leukemogenic mutations. Newer molecular therapies targeting aberrant biological pathways are currently under investigation with a few moving closer to clinical use...
May 4, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31026747/context-dependent-genetic-interactions-in-cancer
#25
REVIEW
Luisa Henkel, Benedikt Rauscher, Michael Boutros
Genetic co-dependencies have been found in many contexts, from processes during the development of organisms to many diseases in man, including cancer. Genetic interactions - and in particular synthetic lethal phenotypes - have provided fundamental insights into the genetic architecture of cells and identified potential new opportunities for therapeutic interventions. However, recent studies also demonstrated that genetic interactions are highly context dependent and synthetic lethal interactions in one tumor context might not be translatable to others...
April 23, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30974317/genetic-interaction-networks-in-cancer-cells
#26
REVIEW
Barbara Mair, Jason Moffat, Charles Boone, Brenda J Andrews
The genotype-to-phenotype relationship in health and disease is complex and influenced by both an individual's environment and their unique genome. Personal genetic variants can modulate gene function to generate a phenotype either through a single gene effect or through genetic interactions involving two or more genes. The relevance of genetic interactions to disease phenotypes has been particularly clear in cancer research, where an extreme genetic interaction, synthetic lethality, has been exploited as a therapeutic strategy...
April 8, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30954761/dissecting-parp-inhibitor-resistance-with-functional-genomics
#27
REVIEW
Stephen J Pettitt, Christopher J Lord
The poly-(ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib was the first licenced cancer drug that targeted an inherited form of cancer, namely ovarian cancers caused by germline BRCA1 or BRCA2 gene mutations. Multiple different PARPi have now been approved for use in a wider group of gynaecological cancers as well as for the treatment of BRCA-gene mutant breast cancer. Despite these advances, resistance to PARPi is a common clinical phenotype. Understanding, at the molecular level, how tumour cells respond to PARPi has the potential to inform how these drugs should be used clinically and since the discovery of this drug class, multiple different functional genomic strategies have been employed to dissect PARPi sensitivity and resistance...
April 4, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30954760/deciphering-mechanisms-of-response-and-resistance-in-large-scale-mouse-cancer-screens
#28
REVIEW
Anirudh Prahallad, Michael Rugaard Jensen, Emilie Anne Chapeau
Acquired resistance is a major limitation for the successful treatment of cancer patients. Although numerous efficacious cancer therapeutics have been developed in the past decades, resistance arises due to a variety of reasons including tumoral genetic alterations, or modulation of factors in the tumor environment. Understanding the mechanistic reasons for tumor relapse supports the identification of novel combination therapies that could lead to more durable responses. Here, we will review large-scale in vivo screens in pre-clinical cancer models that employed genetic and pharmacological agents toward elucidating acquired drug resistance and informing on beneficial combinations to be tested in clinical trials...
April 3, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30951975/functional-genetic-approaches-to-understanding-drug-response-and-resistance
#29
REVIEW
Matthias Hinterndorfer, Johannes Zuber
Drug development remains a slow and expensive process, while the effective use of established therapeutics is widely hampered by our limited understanding of response and resistance mechanisms. Functional-genetic tools such as CRISPR/Cas9, advanced RNAi methods, and targeted protein degradation, together with other emerging technologies such as time-resolved and single-cell transcriptomics, fundamentally change the way we can search for candidate therapeutic targets and evaluate them before drug development...
April 2, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30928774/from-cell-lines-to-living-biosensors-new-opportunities-to-prioritize-cancer-dependencies-using-ex-vivo-tumor-cultures
#30
REVIEW
Yuen-Yi Tseng, Jesse S Boehm
Precision cancer medicine is based on the ability to predict the dependencies of a given tumor from its molecular makeup. These dependencies can be exploited with targeted, cytotoxic and/or immunity-inducing therapeutics. Ongoing efforts to perform genomic and cellular analyses on clinically annotated patient tumors are powerful, but bounded to existing therapies and focused cohorts. Here, we describe how living tumor material is increasingly being used in the generation of a systematic laboratory-based functional map of cancer dependencies (a 'Cancer Dependency Map')...
March 28, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30921673/modelling-chromosome-structural-and-copy-number-changes-to-understand-cancer-genomes
#31
REVIEW
Maja Kneissig, Sara Bernhard, Zuzana Storchova
Cancer cells differ from healthy cells by genetic information that is massively altered not only by point mutations and small insertions and deletions, but also by large scale changes such as chromosomal rearrangements as well as gains and losses of individual chromosomes or entire chromosome sets. How exactly large-scale chromosomal abnormalities contribute to tumorigenesis has been difficult to study. Remarkable progress has been recently made thanks to in vitro models that mimic large-scale chromosomal aberrations and allow their systematic analysis...
March 25, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30877988/functional-screening-to-identify-senescence-regulators-in-cancer
#32
REVIEW
Amaia Lujambio, Ana Banito
Cellular senescence is implicated in numerous biological processes, and can play pleiotropic, sometimes opposing, roles in cancer. Several triggers, cell types, contexts, and senescence-associated phenotypes introduce a multitude of possibilities when studying this process and its biological consequences. Recent studies continue to characterize cellular senescence at different levels, using a combination of functional screens, in silico analysis, omics characterizations and more targeted studies. However, a comprehensive analysis of its context-dependent effects and multiple phenotypes is required...
March 13, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30852338/large-scale-compound-screens-and-pharmacogenomic-interactions-in-cancer
#33
REVIEW
Ultan McDermott
In the last decade, we have witnessed tremendous advances in our understanding of the landscape of the molecular alterations that underpin many of the most prevalent cancers, in the use of automated high throughput platforms for high-throughput drug screens in cancer cells, in the creation of more clinically relevant cancer cell models, in the application of CRISPR genetic screens for novel target identification, and lastly in the development of more useful computational approaches in the pursuit of biomarkers of drug response...
March 7, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30844513/organoid-models-for-translational-pancreatic-cancer-research
#34
REVIEW
Hervé Tiriac, Dennis Plenker, Lindsey A Baker, David A Tuveson
Despite recent advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) still retains the worst survival rate of common malignancies. Late diagnosis and lack of curative therapeutic options are the most pressing clinical problems for this disease. Therefore, there is a need for patient models and biomarkers that can be applied in the clinic to identify the most effective therapy for a patient. Pancreatic ductal organoids are ex-vivo models of PDAC that can be established from very small biopsies, enabling the study of localized, advanced, and metastatic patients...
March 4, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30844512/exploiting-rare-driver-mutations-for-precision-cancer-medicine
#35
REVIEW
Claudia Scholl, Stefan Fröhling
Catalyzed by the ability to develop precision therapies targeting the unique genetic changes that drive individual tumors, sequencing patients' tumor genomes is an increasingly common practice in oncology. In most cancer types, however, a limited number of common mutations are accompanied by a plethora of low-frequency variants whose functional consequences and clinical actionability are often unknown. We here illustrate that this 'long tail' of infrequent molecular alterations includes oncogenic drivers of biological significance that can be the genetic basis of extraordinary responses to systemic cancer therapies...
March 4, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30554668/editorial-overview-the-history-geography-and-adaptation-of-human-genes-a-tribute-to-l-luca-cavalli-sforza
#36
EDITORIAL
Brenna M Henn, Lluis Quintana-Murci
No abstract text is available yet for this article.
December 2018: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30522870/the-evolutionary-history-of-southern-africa
#37
REVIEW
Francesco Montinaro, Cristian Capelli
The genomic variability of Southern African groups is characterized by an exceptional degree of diversity, which is the result of long-term local evolutionary history, migrations and gene-flow. Over the last few years several investigations have identified and described signatures related to these processes, revealing how ancient and more recent events have shaped the structure and ancestry composition of local populations. Here we discuss recent insights into the genetic history of the Southernmost part of the African continent provided by the analysis of modern and ancient genomes...
December 2018: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30423527/clarifying-distinct-models-of-modern-human-origins-in-africa
#38
REVIEW
Brenna M Henn, Teresa E Steele, Timothy D Weaver
Accumulating genomic, fossil and archaeological data from Africa have led to a renewed interest in models of modern human origins. However, such discussions are often discipline-specific, with limited integration of evidence across the different fields. Further, geneticists typically require explicit specification of parameters to test competing demographic models, but these have been poorly outlined for some scenarios. Here, we describe four possible models for the origins of Homo sapiens in Africa based on published literature from paleoanthropology and human genetics...
December 2018: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30366252/genomic-inference-using-diffusion-models-and-the-allele-frequency-spectrum
#39
REVIEW
Aaron P Ragsdale, Claudia Moreau, Simon Gravel
Evolutionary, biological, and demographic processes together shape observed variation in populations. Understanding how these processes influence variation allows us to infer past demography and the nature of selection in populations. Forward in time models such as the diffusion approximation provide a powerful tool for performing inference based on the distribution of allele frequencies. Here, we discuss recent computational developments and their application to reconstructing human demographic history. Using whole-genome sequence data for 797 French Canadian individuals, we assess the neutrality of synonymous variants and show that selection can bias inferred demography, mutation rates, and distributions of fitness effects...
December 2018: Current Opinion in Genetics & Development
https://read.qxmd.com/read/30366251/human-evolutionary-history-of-eastern-africa
#40
REVIEW
Ludovica Molinaro, Luca Pagani
Since the discovery of the first hominin fossils, East Africa has been in the spotlight of palaeo-anthropological investigation for its role as a potential cradle of humanity and as a gateway out of Africa. With the advent of the genomic era an ever increasing amount of information has started to complement this notion, and to place the area within a broader, Pan-African scenario. Here we examine the most recent genetic and fossil results that recapitulate the last hundreds of thousands of years of human evolution in the area, and point to a number of uncharted avenues that may complement the emerging scenario in the coming years...
December 2018: Current Opinion in Genetics & Development
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