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Current Opinion in Genetics & Development

J Omar Yáñez-Cuna, Bas van Steensel
Lamina-associated domains (LADs) are large genomic regions that interact with the nuclear lamina (NL) and help to guide the spatial folding of chromosomes in the interphase nucleus. LADs have been linked to gene repression and other functions. Recent studies have begun to uncover some of the molecular players that drive LAD-NL interactions. A picture emerges in which DNA sequence, chromatin components and nuclear lamina proteins play an important role. Complementary to this, imaging and single-cell genomics approaches have revealed that some LAD-NL interactions are variable from cell to cell, while others are very stable...
January 17, 2017: Current Opinion in Genetics & Development
D'Juan T Farmer, Michael T McManus
The surface ectoderm is the source of ectodermal appendages including hair, teeth, and many glands. The development and function of ectodermal appendages has been researched extensively, but many of the molecular mechanisms that govern the developmental programs of ectodermal appendages remain elusive. While several protein-coding genes are established as key regulators of ectodermal appendage development, the role of noncoding RNAs is an emerging area of investigation. This review highlights recent advances in studies of microRNA-mediated control of ectodermal appendage development using mouse models...
January 16, 2017: Current Opinion in Genetics & Development
Máté Pálfy, Shai R Joseph, Nadine L Vastenhouw
After fertilization, the embryonic genome is inactive until transcription is initiated during the maternal-to-zygotic transition. How the onset of transcription is regulated in a precisely timed manner, however, is a long standing question in biology. Several mechanisms have been shown to contribute to the temporal regulation of genome activation but none of them can fully explain the general absence of transcription as well the gene specific onset that follows. Here we review the work that has been done toward elucidating the mechanisms underlying the temporal regulation of transcription in embryos...
January 11, 2017: Current Opinion in Genetics & Development
Mitchell J Machiela, Stephen J Chanock
Clonal mosaicism arises when a postzygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. It has also been postulated to be an important mechanism for functional cellular diversity, including the brain...
January 6, 2017: Current Opinion in Genetics & Development
Antonio Ca Meireles-Filho, Bart Deplancke
In the mammalian gastrointestinal tract, distinct types of cells, including epithelial cells and macrophages, collaborate to eliminate ingested pathogens while striving to preserve the commensal microbiota. The underlying innate immune response is driven by significant gene expression changes in each cell, and recent work has provided novel insights into the gene regulatory mechanisms that mediate such transcriptional changes. These mechanisms differ from those underlying the canonical cellular differentiation model in which a sequential deposition of DNA methylation and histone modification marks progressively restricts the chromatin landscape...
December 20, 2016: Current Opinion in Genetics & Development
Christopher M Vockley, Alejandro Barrera, Timothy E Reddy
Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment...
December 13, 2016: Current Opinion in Genetics & Development
Elizabeth T Wiles, Eric U Selker
Polycomb Repressive Complex 2 (PRC2) is a multiprotein complex that catalyzes the methylation of lysine 27 on histone H3 (H3K27me). This histone modification is a feature of facultative heterochromatin in many eukaryotes and maintains transcriptional repression established during early development. Understanding how PRC2 targets regions of the genome to be methylated remains poorly understood. Different cell types can show disparate patterns of H3K27me, and chromatin perturbations, such as loss of marks of constitutive heterochromatin, can cause redistribution of H3K27me, implying that DNA sequence, per se, is not sufficient to define the distribution of this mark...
December 8, 2016: Current Opinion in Genetics & Development
Xue Qing David Wang, Josée Dostie
There are many ways in which cells may not adequately behave or respond to their environment, and the molecular mechanisms leading to these defects are as diverse as they are many. In this review, we report on how spatial chromatin organization contributes to the proper expression of genes, relating how CTCF-one of its main architects-contributes to gene regulation. We also touch on the emerging role of long noncoding RNAs in shaping chromatin organization and activity. The HOX gene clusters have been used as paradigm in the study of various biological pathways, and the overview we provide gives emphasis to what research on these loci has revealed about chromatin architecture and its regulation in the control of gene expression...
December 8, 2016: Current Opinion in Genetics & Development
Luisa Cimmino, Iannis Aifantis
Ten-eleven-translocation (TET) proteins oxidize 5-methylcytosine (5mC) to form stable or transient modifications (oxi-mCs) in the mammalian genome. Genome-wide mapping and protein interaction studies have shown that 5mC and oxi-mCs have unique distribution patterns and alternative roles in gene expression. In addition, oxi-mCs may interact with specific chromatin regulators, transcription factors and DNA repair proteins to maintain genomic integrity or alter DNA replication and transcriptional elongation rates...
December 7, 2016: Current Opinion in Genetics & Development
Ignacio Maeso, Rafael D Acemel, José Luis Gómez-Skarmeta
The recent advances in our understanding of the 3D organization of the chromatin together with an almost unlimited ability to detect cis-regulatory elements genome-wide using different biochemical signatures has provided us with an unprecedented power to study gene regulation. It is now possible to profile the complete regulatory apparatus controlling the spatio-temporal expression of any given gene, the so-called gene Regulatory Landscapes (RLs). Here we review several studies over the last two years demonstrating the functional consequences of altering RL structure in development, disease and evolution...
November 11, 2016: Current Opinion in Genetics & Development
Andrew Seeber, Susan M Gasser
Chromatin is organized and segmented into a landscape of domains that serve multiple purposes. In contrast to transcription, which is controlled by defined sequences at distinct sites, DNA damage can occur anywhere. Repair accordingly must occur everywhere, yet it is inevitably affected by its chromatin environment. In this review, we summarize recent work investigating how changes in chromatin organization facilitate and/or guide DNA double-strand break repair. In addition, we examine new live cell studies on the dynamics of chromatin and the mechanisms that regulate its movement...
October 31, 2016: Current Opinion in Genetics & Development
Joshua M Akey, Anna Di Rienzo
No abstract text is available yet for this article.
December 2016: Current Opinion in Genetics & Development
Marcia Holsbach Beltrame, Meagan A Rubel, Sarah A Tishkoff
Africa is the origin of anatomically modern humans and a continent of linguistic, cultural, environmental, phenotypic, and genetic diversity. However, African populations remain underrepresented in genetic studies, which have largely focused on individuals with European and Asian ancestry. The expansion of high-throughput 'omic' technologies to interrogate multiple tissue types across many biomolecules-DNA, proteins, epigenetic modifications, metabolites, and others-has heralded a new era of investigation into African history...
December 2016: Current Opinion in Genetics & Development
Yuval B Simons, Guy Sella
Over the past decade, there has been both great interest and confusion about whether recent demographic events-notably the Out-of-Africa-bottleneck and recent population growth-have led to differences in mutation load among human populations. The confusion can be traced to the use of different summary statistics to measure load, which lead to apparently conflicting results. We argue, however, that when statistics more directly related to load are used, the results of different studies and data sets consistently reveal little or no difference in the load of non-synonymous mutations among human populations...
December 2016: Current Opinion in Genetics & Development
Lauren Alpert Sugden, Sohini Ramachandran
Human population genomic studies have repeatedly observed a decrease in heterozygosity and an increase in linkage disequilibrium with geographic distance from Africa. While multiple demographic models can generate these patterns, many studies invoke the serial founder effect model, in which populations expand from a single origin and each new population's founders represent a subset of genetic variation in the previous population. The model assumes no admixture with archaic hominins, however, recent studies have identified loci in Homo sapiens bearing signatures of archaic introgression...
December 2016: Current Opinion in Genetics & Development
Martin Kuhlwilm, Marc de Manuel, Alexander Nater, Maja P Greminger, Michael Krützen, Tomas Marques-Bonet
The great apes are the closest living relatives of humans. Chimpanzees and bonobos group together with humans, while gorillas and orangutans are more divergent from humans. Here, we review insights into their evolution pertaining to the topology of species and subspecies and the reconstruction of their demography based on genome-wide variation. These advances have only become possible recently through next-generation sequencing technologies. Given the close relationship to humans, they provide an important evolutionary context for human genetics...
December 2016: Current Opinion in Genetics & Development
Feng Gao, Alon Keinan
The advent of next-generation sequencing technology has allowed the collection of vast amounts of genetic variation data. A recurring discovery from studying larger and larger samples of individuals had been the extreme, previously unexpected, excess of very rare genetic variants, which has been shown to be mostly due to the recent explosive growth of human populations. Here, we review recent literature that inferred recent changes in population size in different human populations and with different methodologies, with many pointing to recent explosive growth, especially in European populations for which more data has been available...
December 2016: Current Opinion in Genetics & Development
Kaustubh Adhikari, Javier Mendoza-Revilla, Juan Camilo Chacón-Duque, Macarena Fuentes-Guajardo, Andrés Ruiz-Linares
Latin Americans arguably represent the largest recently admixed populations in the world. This reflects a history of massive settlement by immigrants (mostly Europeans and Africans) and their variable admixture with Natives, starting in 1492. This process resulted in the population of Latin America showing an extensive genetic and phenotypic diversity. Here we review how genetic analyses are being applied to examine the demographic history of this population, including patterns of mating, population structure and ancestry...
December 2016: Current Opinion in Genetics & Development
Torsten Günther, Mattias Jakobsson
Genomic information from ancient human remains is beginning to show its full potential for learning about human prehistory. We review the last few years' dramatic finds about European prehistory based on genomic data from humans that lived many millennia ago and relate it to modern-day patterns of genomic variation. The early times, the Upper Paleolithic, appears to contain several population turn-overs followed by more stable populations after the Last Glacial Maximum and during the Mesolithic. Some 11000 years ago the migrations driving the Neolithic transition start from around Anatolia and reach the north and the west of Europe millennia later followed by major migrations during the Bronze Age...
December 2016: Current Opinion in Genetics & Development
John Novembre, Benjamin M Peter
Empowered by modern genotyping and large samples, population structure can be accurately described and quantified even when it only explains a fraction of a percent of total genetic variance. This is especially relevant and interesting for humans, where fine-scale population structure can both confound disease-mapping studies and reveal the history of migration and divergence that shaped our species' diversity. Here we review notable recent advances in the detection, use, and understanding of population structure...
December 2016: Current Opinion in Genetics & Development
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