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Current Opinion in Genetics & Development

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...
November 10, 2018: 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
Brenna M Henn, Lluis Quintana-Murci
No abstract text is available yet for this article.
December 2018: Current Opinion in Genetics & Development
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
Knut Woltjen, Alex Bortvin
No abstract text is available yet for this article.
October 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
Effie Apostolou, Matthias Stadtfeld
The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallmarks and roadmaps of iPSC formation by describing relative kinetics of transcriptional, protein and epigenetic changes, including alterations in DNA methylation and histone modifications. Recently, technological advancements such as single-cell analyses, high-resolution genome-wide chromatin assays and more efficient reprogramming systems have been used to challenge and refine our understanding of the reprogramming process...
October 2018: Current Opinion in Genetics & Development
Abhijit Shukla, Danwei Huangfu
Large portions of the human genome harbor functional noncoding elements, which can regulate a variety of biological processes and have important implications for disease risk and therapeutic outcomes. However, assigning specific functions to noncoding sequences remains a major challenge. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) systems have emerged as a powerful approach for targeted genome and epigenome perturbation. CRISPR systems are now harnessed for high-throughput screening of the noncoding genome to uncover functional regulatory elements and to define their precise functions with superior speed...
October 2018: Current Opinion in Genetics & Development
Fyodor D Urnov
Genome editing with engineered nucleases (zinc finger, TAL effector, or CRISPR/Cas9-based) enables `write' access to regulatory programs executed by primary human cells. A decade of its clinical development, along with a reduction of conventional gene therapy to medical and commercial practice, has made cell reprogramming via editing a viable clinical modality. Reviewed here are the first examples of this to enter the clinic: ex vivo edited T cells for infectious disease and cancer, and hematopoietic stem/progenitor cells for the hemoglobinopathies...
October 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
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