scholarly journals Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

2019 ◽  
Author(s):  
Tina Wang ◽  
Jianzhu Ma ◽  
Andrew N. Hogan ◽  
Samson Fong ◽  
Katherine Licon ◽  
...  
Keyword(s):  
Gene Networks ◽  
Nonlinear Relationship ◽  
Epigenetic Changes ◽  
Developmental Gene ◽  
Molecular Events ◽  
Mammalian Genomes ◽  
Age Range ◽  
Labrador Retrievers ◽  
Evolutionary Comparisons ◽  
Diagnostic Age

SUMMARYMammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104 Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones.

scholarly journals Butterfly Mimicry Polymorphisms Highlight Phylogenetic Limits of Gene Reuse in the Evolution of Diverse Adaptations

2019 ◽  
Vol 36 (12) ◽  
pp. 2842-2853 ◽  
Author(s):  
Nicholas W VanKuren ◽  
Darli Massardo ◽  
Sumitha Nallu ◽  
Marcus R Kronforst
Keyword(s):  
Phylogenetic Relationship ◽  
Gene Networks ◽  
Genetic Basis ◽  
Color Pattern ◽  
Butterfly Wing ◽  
Color Patterns ◽  
Developmental Gene ◽  
Genome Region ◽  
Correlated Factors ◽  
Unique Genes

Abstract Some genes have repeatedly been found to control diverse adaptations in a wide variety of organisms. Such gene reuse reveals not only the diversity of phenotypes these unique genes control but also the composition of developmental gene networks and the genetic routes available to and taken by organisms during adaptation. However, the causes of gene reuse remain unclear. A small number of large-effect Mendelian loci control a huge diversity of mimetic butterfly wing color patterns, but reasons for their reuse are difficult to identify because the genetic basis of mimicry has primarily been studied in two systems with correlated factors: female-limited Batesian mimicry in Papilio swallowtails (Papilionidae) and non-sex-limited Müllerian mimicry in Heliconius longwings (Nymphalidae). Here, we break the correlation between phylogenetic relationship and sex-limited mimicry by identifying loci controlling female-limited mimicry polymorphism Hypolimnas misippus (Nymphalidae) and non-sex-limited mimicry polymorphism in Papilio clytia (Papilionidae). The Papilio clytia polymorphism is controlled by the genome region containing the gene cortex, the classic P supergene in Heliconius numata, and loci controlling color pattern variation across Lepidoptera. In contrast, female-limited mimicry polymorphism in Hypolimnas misippus is associated with a locus not previously implicated in color patterning. Thus, although many species repeatedly converged on cortex and its neighboring genes over 120 My of evolution of diverse color patterns, female-limited mimicry polymorphisms each evolved using a different gene. Our results support conclusions that gene reuse occurs mainly within ∼10 My and highlight the puzzling diversity of genes controlling seemingly complex female-limited mimicry polymorphisms.

scholarly journals Development of acute megakaryoblastic leukemia in Down syndrome is associated with sequential epigenetic changes

Blood ◽  
2013 ◽  
Vol 122 (14) ◽  
pp. e33-e43 ◽  
Author(s):  
Sébastien Malinge ◽  
Tim Chlon ◽  
Louis C. Doré ◽  
Rhett P. Ketterling ◽  
Martin S. Tallman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Gene Networks ◽  
Specific Gene ◽  
Epigenetic Changes ◽  
Acute Megakaryoblastic Leukemia ◽  
Megakaryoblastic Leukemia ◽  
Biological Features ◽  
Key Points

Key Points DNA methylation changes during the development of DS-AMKL occur in sequential waves of opposing losses and gains of methylation. Each wave of DNA methylation abnormalities targets specific gene networks that contribute to distinct biological features of the disease.

scholarly journals The Emerging Role of Ten-Eleven Translocation 1 in Epigenetic Responses to Environmental Exposures

2020 ◽  
Vol 13 ◽  
pp. 251686572091015 ◽  
Author(s):  
Tao Zhu ◽  
Anthony P Brown ◽  
Hong Ji
Keyword(s):  
Therapeutic Potential ◽  
Critical Role ◽  
Environmental Exposures ◽  
Epidemiological Studies ◽  
Epigenetic Changes ◽  
Molecular Processes ◽  
Molecular Events ◽  
Negative Impacts ◽  
The Impact

Mounting evidence from epidemiological studies and animal models has linked exposures to environmental factors to changes in epigenetic markers, especially in DNA methylation. These epigenetic changes may lead to dysregulation of molecular processes and functions and mediate the impact of environmental exposures in complex diseases. However, detailed molecular events that result in epigenetic changes following exposures remain unclear. Here, we review the emerging evidence supporting a critical role of ten-eleven translocation 1 (TET1) in mediating these processes. Targeting TET1 and its associated pathways may have therapeutic potential in alleviating negative impacts of environmental exposures, preventing and treating exposure-related diseases.

scholarly journals Topological isolation of developmental regulators in mammalian genomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hua-Jun Wu ◽  
Alexandro Landshammer ◽  
Elena K. Stamenova ◽  
Adriano Bolondi ◽  
Helene Kretzmer ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Purifying Selection ◽  
Gene Isolation ◽  
Regulatory Control ◽  
Developmental Gene ◽  
Distal Enhancer ◽  
Precise Control ◽  
Mammalian Genomes ◽  
Loop Domains ◽  
Mammalian Gene Expression

AbstractPrecise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, we found that germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings highlight the importance of developmental gene isolation through chromosomal folding structures as a mechanism to ensure their proper expression.

scholarly journals Estimating optimal sparseness of developmental gene networks using a semi-quantitative model

PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0176492
Author(s):  
Natsuhiro Ichinose ◽  
Tetsushi Yada ◽  
Hiroshi Wada
Keyword(s):  
Gene Networks ◽  
Quantitative Model ◽  
Developmental Gene

scholarly journals The core promoter composition establishes a new dimension in developmental gene networks

Nucleus ◽  
2014 ◽  
Vol 5 (4) ◽  
pp. 298-303 ◽  
Author(s):  
Yonathan Zehavi ◽  
Anna Sloutskin ◽  
Olga Kuznetsov ◽  
Tamar Juven-Gershon
Keyword(s):  
Gene Networks ◽  
Core Promoter ◽  
Developmental Gene ◽  
The Core

A CELLULAR AUTOMATON TO MODEL THE DEVELOPMENT OF PRIMARY SHOOT MERISTEMS OF ARABIDOPSIS THALIANA

2007 ◽  
Vol 05 (02b) ◽  
pp. 641-650 ◽  
Author(s):  
ILYA R. AKBERDIN ◽  
EVGENIY A. OZONOV ◽  
VICTORIA V. MIRONOVA ◽  
NADEZDA A. OMELYANCHUK ◽  
VITALY A. LIKHOSHVAI ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cellular Automaton ◽  
Gene Networks ◽  
Cell Types ◽  
Shoot Meristem ◽  
Regulatory Mechanisms ◽  
Developmental Gene ◽  
Complex Process ◽  
Different Cell Types ◽  
Shoot Meristems

Development of organisms is a very complex process in which a lot of gene networks of different cell types are integrated. Development of a cellular automaton (Ermentrout and Edelshtein-Keshet, J Theor Biol160:97–133, 1993) that models the morphodynamics of different cell types is the first step in understanding and analysis of the regulatory mechanisms underlying the functioning of developmental gene networks. A model of a cellular automaton has been developed, which simulates the embryonic development of shoot meristem in Arabidopsis thaliana. The model adequately describes the basic stages in development of this organ in wild and mutant types.

scholarly journals Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia

2020 ◽  
Vol 21 (18) ◽  
pp. 6720
Author(s):  
Linda Fabris ◽  
Jaroslav Juracek ◽  
George Calin
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Networks ◽  
Lymphocytic Leukemia ◽  
Base Pairs ◽  
Cancer Hallmarks ◽  
Cellular Processes ◽  
Tumor Onset ◽  
Molecular Events ◽  
Non Coding Rnas

The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent a heterogeneous group of transcripts, ranging from a few base pairs to several kilobases, that are able to regulate gene networks and intracellular pathways by interacting with DNA, transcripts or proteins. Deregulation of ncRNAs impinge on several cellular responses and can play a major role in each single hallmark of cancer. This review will focus on the most important short and long non-coding RNAs in chronic lymphocytic leukemia (CLL), highlighting their implications as potential biomarkers and therapeutic targets as they relate to the well-established hallmarks of cancer. The key molecular events in the onset of CLL will be contextualized, taking into account the role of the “dark matter” of the genome.

Isolated Articular Fractures of the Canine Talus: Diagnosis and Signalment in Fourteen Dogs

2020 ◽  
Author(s):  
Elena Carbonell Buj ◽  
Neil Burton ◽  
John R. Mosley ◽  
Richard L. Meeson ◽  
Alison Major ◽  
...  
Keyword(s):  
Case Series ◽  
Inclusion Criteria ◽  
Bone Pathology ◽  
Diagnostic Challenge ◽  
Articular Fractures ◽  
Complex Anatomy ◽  
Fracture Configuration ◽  
Talar Fractures ◽  
Age Range ◽  
Labrador Retrievers

Abstract Objective The aim of this retrospective multicentre case series was to describe signalment, presenting signs and imaging findings in dogs with isolated articular fractures of the talus. Study Design Medical records (2008–2019) of dogs with isolated articular talar fractures were reviewed. Results Fourteen dogs met the inclusion criteria; affected breeds were four German Pointer (three shorthair and one wirehaired), three Labrador Retrievers, two Rottweilers, two Springer Spaniels, one cross breed, one Greyhound and one Great Münsterländer. The age range was 1 to 8 years with a median of 4.7 years. Lameness was usually acute in onset and had been present for a range of 4 to 540 days prior to referral.The most common fracture configuration involved the lateral trochlear ridge only (n = 9). Two of the fourteen fractures affected both trochlear ridges. Thirteen dogs were initially assessed radiographically with classic orthogonal views, but a fracture was only visible in five cases. The remainder were confirmed with further radiographic projections (n = 4) or computed tomography (n = 5). In one case, the lameness was located to the tarsus by scintigraphy. Conclusion Isolated articular fracture of the talus is rare and may prove a diagnostic challenge due to the varied presentations and complex anatomy of the bone. Pathology of the talus may be suspected in any case of lameness localized to the tarsus and oblique/skyline radiographic views or advanced imaging should be performed if standard radiographic views are unremarkable.

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