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Current Opinion in Genetics & Development

Georgina A Stooke-Vaughan, Otger Campàs
During embryogenesis, tissues and organs are progressively shaped into their functional morphologies. While the information about tissue and organ shape is encoded genetically, the sculpting of embryonic structures in the 3D space is ultimately a physical process. The control of physical quantities involved in tissue morphogenesis originates at cellular and subcellular scales, but it is their emergent behavior at supracellular scales that guides morphogenetic events. In this review, we highlight the physical quantities that can be spatiotemporally tuned at supracellular scales to sculpt tissues and organs during embryonic development of animal species, and connect them to the cellular and molecular mechanisms controlling them...
October 31, 2018: Current Opinion in Genetics & Development
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...
October 23, 2018: Current Opinion in Genetics & Development
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...
October 23, 2018: Current Opinion in Genetics & Development
Mait Metspalu, Mayukh Mondal, Gyaneshwer Chaubey
South Asia is home for more than a billion people culturally structured into innumerable groups practicing different levels of endogamy. Linguistically South Asia is broadly characterized by four major language families which has served as access way for disentangling the genetic makings of South Asia. In this review we shall give brief account on the recent developments in the field. Advances are made in two fronts simultaneously. Whole genome characterisation of many extant South Asians paint the picture of the genetic diversity and its implications to health-care...
October 1, 2018: Current Opinion in Genetics & Development
Sarah Jacquelyn Smith, Mark Rebeiz, Lance Davidson
The development of anatomical structures is complex, beginning with patterning of gene expression by multiple gene regulatory networks (GRNs). These networks ultimately regulate the activity of effector molecules, which in turn alter cellular behavior during development. Together these processes biomechanically produce the three-dimensional shape that the anatomical structure adopts over time. However, the interfaces between these processes are often overlooked and also include counter-intuitive feedback mechanisms...
September 29, 2018: Current Opinion in Genetics & Development
Nobuo Sasaki, Hans Clevers
Intra-tumor heterogeneity (genotypic and functional diversity among cancer cells within the same tumor) represents one of the key challenges in cancer medicine. As heterogeneity of cancer cells constitutes an important parameter in the development of therapy resistance, an accurate assessment of intra-tumor heterogeneity is essential for the prediction of drug resistance and development of effective treatment. In this review, we evaluate primary patient derived-tumor organoid technology as a new tool for colorectal cancer research and treatment...
September 24, 2018: Current Opinion in Genetics & Development
Pongsakorn Wangkumhang, Garrett Hellenthal
The increasing availability of large-scale autosomal genetic variation data sampled from world-wide geographic areas, coupled with advances in the statistical methodology to analyse these data, is showcasing the power of DNA as a major tool to gain insights into the demographic history of humans and other organisms. Here we review statistical techniques that shed light on a specific aspect of demography: the detection and description of admixture events where two or more genetically distinct groups intermixed at one or more times in the past...
September 20, 2018: Current Opinion in Genetics & Development
Alicia R Martin, Solomon Teferra, Marlo Möller, Eileen G Hoal, Mark J Daly
Human genetic studies have long been vastly Eurocentric, raising a key question about the generalizability of these study findings to other populations. Because humans originated in Africa, these populations retain more genetic diversity, and yet individuals of African descent have been tremendously underrepresented in genetic studies. The diversity in Africa affords ample opportunities to improve fine-mapping resolution for associated loci, discover novel genetic associations with phenotypes, build more generalizable genetic risk prediction models, and better understand the genetic architecture of complex traits and diseases subject to varying environmental pressures...
September 18, 2018: Current Opinion in Genetics & Development
Zijun Sun, Yusuke Toyama
Epithelium undergoes complex deformations during morphogenesis. Many of these deformations rely on the remodelling of apical cell junctions by actomyosin-based contractile force and this has been a major research interest for many years. Recent studies have shown that cells can use additional mechanisms that are not directly driven by actomyosin contractility to alter cell shape and movement, in three-dimensional (3D) space and time. In this review, we focus on a number of these mechanisms, including basolateral cellular protrusion, lateral shift of cell polarity, cytoplasmic flow, regulation of cell volume, and force transmission between cell-cell adhesion and cell-extracellular matrix adhesion, and describe how they underlie Drosophila epithelia deformations...
September 11, 2018: Current Opinion in Genetics & Development
Noah Snyder-Mackler, Amanda J Lea
Both the social and physical environment shape health, reproduction, and survival across many species, and identifying how these effects manifest at the molecular level has long been a priority in medicine and evolutionary biology. The recent rise of functional genomics has enabled researchers to gain new insights into how environmental inputs shape variation in gene regulation, and consequently, downstream organism-level traits. Here, we discuss recent work on this topic, as well as key knowledge gaps. Research in this area spans a wide range of taxa, but we focus our review on mammalian species because of their close evolutionary proximity to humans and because of their relevance for understanding human health...
August 21, 2018: Current Opinion in Genetics & Development
Gillian M Belbin, Maria A Nieves-Colón, Eimear E Kenny, Andres Moreno-Estrada, Christopher R Gignoux
Hispanic/Latino (H/L) populations, although linked by culture and aspects of shared history, reflect the complexity of history and migration influencing the Americas. The original settlement by indigenous Americans, followed by postcolonial admixture from multiple continents, has yielded localized genetic patterns. In addition, numerous H/L populations appear to have signatures of pre-colonization and post-colonization bottlenecks, indicating that tens of millions of H/Ls may harbor signatures of founder effects today...
August 17, 2018: Current Opinion in Genetics & Development
R Marisol Herrera-Perez, Karen E Kasza
Epithelial cell rearrangements and cell shape changes are fundamental mechanisms by which cells build and shape elaborate and diverse tissue architectures from simple tissue sheets. These cell behaviors are regulated by a complex interplay between physical and biochemical mechanisms, many of which have been uncovered in recent studies in Drosophila. While the regulation of these cell behaviors is still under investigation, emerging technologies are being used to gain experimental control over these behaviors, opening new possibilities for designing and engineering tissue structures...
August 10, 2018: Current Opinion in Genetics & Development
Etienne Patin, Lluis Quintana-Murci
Central Africa, a forested region that supports an exceptionally high biodiversity, hosts the world's largest group of hunter-gatherers, who live in close proximity with groups that have adopted agriculture over the past 5000 years. Our understanding of the prehistory of these populations has been dramatically hampered by the almost total absence of fossil remains in this region, a limitation that has recently been circumvented by population genomics approaches. Different studies have estimated that ancestors of rainforest hunter-gatherers and Bantu-speaking farmers separated more than 60 000 years ago, supporting the occurrence of ancient population structure in Africa since the Late Pleistocene...
August 10, 2018: Current Opinion in Genetics & Development
Krishna R Veeramah
There has been an undercurrent of intellectual tension between geneticists studying human population history and archaeologists for almost 40 years. The rapid development of paleogenomics, with geneticists working on the very material discovered by archaeologists, appears to have recently heightened this tension. The relationship between these two fields thus far has largely been of a multidisciplinary nature, with archaeologists providing the raw materials for sequencing, as well as a scaffold of hypotheses based on interpretation of archaeological cultures from which the geneticists can ground their inferences from the genomic data...
August 3, 2018: Current Opinion in Genetics & Development
Guy B Blanchard, Jocelyn Étienne, Nicole Gorfinkiel
We review recent developments in the understanding of the biomechanics of apicomedial actomyosin and how its contractility can tense and deform tissue. Myosin pulses are driven by a biochemical oscillator but how they are modulated by the mechanical context remains unclear. On the other hand, the emergence of tissue behaviour is highly dependent on the material properties of actin, on how strongly components are connected and on the influence of neighbouring tissues. We further review the use of constitutive equations in exploring the mechanics of epithelial apices dominated by apicomedial Myosin contractility...
August 1, 2018: Current Opinion in Genetics & Development
Melissa Ilardo, Rasmus Nielsen
Modern humans inhabit most of earth's harshest environments and display a wide array of lifestyles. Biological adaptations, in addition to technological innovations, have enabled these geographical and cultural explorations. The study of these adaptations helps not only to fundamentally understand our evolution as a species, but also may have increasing relevance as genomics transforms fields such as personalized medicine. Here we review three cultural and environmental shifts that have brought about adaptations in modern humans; the arctic, high altitudes, and a subsistence dependent on breath-hold diving...
August 1, 2018: Current Opinion in Genetics & Development
Jeffrey P Spence, Matthias Steinrücken, Jonathan Terhorst, Yun S Song
Studying how diverse human populations are related is of historical and anthropological interest, in addition to providing a realistic null model for testing for signatures of natural selection or disease associations. Furthermore, understanding the demographic histories of other species is playing an increasingly important role in conservation genetics. A number of statistical methods have been developed to infer population demographic histories using whole-genome sequence data, with recent advances focusing on allowing for more flexible modeling choices, scaling to larger data sets, and increasing statistical power...
July 26, 2018: Current Opinion in Genetics & Development
Niall P Cooke, Shigeki Nakagome
Approximate Bayesian Computation (ABC) is a flexible statistical tool widely applied to addressing a variety of questions regarding the origin and evolution of humans. The significant growth of genomic scale data from diverse geographic populations has facilitated the use of ABC in modelling the complex processes that underlie human demography and local adaptation. However, a fundamental issue still remains in how to efficiently capture patterns of genetic variation with a set of summary statistics in order to achieve better approximation of Bayesian inference...
July 17, 2018: Current Opinion in Genetics & Development
Anna L Gosling, Elizabeth A Matisoo-Smith
Understanding the timing and processes involved in the human settlement of Australia and the Pacific has significance for addressing some key debates relating to human origins and population expansions worldwide. Despite this, for many years, Pacific populations were seriously under-represented in genetic studies of human origins. The last 15 years, however, have seen some major genetic studies involving Australian and Pacific populations which have shed light on their origins and interactions, and the last five years have seen some major developments that are challenging long-held concepts of Pacific settlement...
July 17, 2018: Current Opinion in Genetics & Development
Stephanie L Schnorr
Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys...
July 13, 2018: Current Opinion in Genetics & Development
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