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We stand on the brink of unprecedented growth in our ability to understand and change the human genome. New reproductive technologies now enable parents to select some genetic traits for their children, and soon it will be possible to begin to shape ourselves as a species. Despite the loud cries of alarm that such a prospect inspires, Ronald Green argues that we will-and we should-undertake the direction of our own evolution. A leader in the bioethics community, Green offers a scientifically and ethically informed view of human genetic self-modification and the possibilities it opens up for a better future. Fears of a terribleBrave New Worldor a new eugenics movement are overblown, he maintains, and in the more likely future, genetic modifications may improve parents' ability to enhance children's lives and may even promote social justice. The author outlines the new capabilities of genomic science, addresses urgent questions of safety that genetic interventions pose, and explores questions of parenting and justice. He also examines the religious implications of gene modification. Babies by design are assuredly in the future, Green concludes, and by making responsible choices as we enter that future, we can incorporate gene technology in a new age of human adventure.

We report the design, synthesis, and assembly of the 1.08-mega-base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new M. mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including \"watermark\" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.

Transcription activator–like effector nucleases (TALENs) are a new technology for modifying the genome at specific loci of interest. Hockemeyer et al . now demonstrate the utility of TALENs for gene targeting in human pluripotent stem cells. Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator–like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).

This book provides an overview of computational analysis of genes and genomes, and of some most notable findings that come out of this work.Foundations of Comparative Genomics presents a historical perspective, beginning with early analysis of individual gene sequences, to present day comparison of gene repertoires encoded by completely sequenced.

Analyzing the effects of multiple promoter motifs on gene expression can be a laborious process. Sharon et al . present a high-throughput method to measure the expression of thousands of designed yeast promoters in a single experiment and use it to reveal new features of transcriptional regulation. Despite extensive research, our understanding of the rules according to which cis -regulatory sequences are converted into gene expression is limited. We devised a method for obtaining parallel, highly accurate gene expression measurements from thousands of designed promoters and applied it to measure the effect of systematic changes in the location, number, orientation, affinity and organization of transcription-factor binding sites and nucleosome-disfavoring sequences. Our analyses reveal a clear relationship between expression and binding-site multiplicity, as well as dependencies of expression on the distance between transcription-factor binding sites and gene starts which are transcription-factor specific, including a striking ∼10-bp periodic relationship between gene expression and binding-site location. We show how this approach can measure transcription-factor sequence specificities and the sensitivity of transcription-factor sites to the surrounding sequence context, and compare the activity of 75 yeast transcription factors. Our method can be used to study both cis and trans effects of genotype on transcriptional, post-transcriptional and translational control.

Capturing and sequencing only the coding regions of the human genome leverages resources in the pursuit of rare disease-causing mutations. Clark et al . compare the performance of three leading exome-capture methods and their advantages over whole-genome sequencing. Whole exome sequencing by high-throughput sequencing of target-enriched genomic DNA (exome-seq) has become common in basic and translational research as a means of interrogating the interpretable part of the human genome at relatively low cost. We present a comparison of three major commercial exome sequencing platforms from Agilent, Illumina and Nimblegen applied to the same human blood sample. Our results suggest that the Nimblegen platform, which is the only one to use high-density overlapping baits, covers fewer genomic regions than the other platforms but requires the least amount of sequencing to sensitively detect small variants. Agilent and Illumina are able to detect a greater total number of variants with additional sequencing. Illumina captures untranslated regions, which are not targeted by the Nimblegen and Agilent platforms. We also compare exome sequencing and whole genome sequencing (WGS) of the same sample, demonstrating that exome sequencing can detect additional small variants missed by WGS.

The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level. Synthetic biology clocks on The genetic circuits approach to synthetic biology uses computer modelling to design small gene networks that function in living cells. Less than a decade after its first successes — the synthetic oscillator and the toggle switch — Jeff Hasty and colleagues have built a population of synchronized Escherichia coli cells by engineering natural 'quorum sensing' genes. Using microfluidics and time-lapse fluorescence microscopy they derive general rules about the factors controlling synchronous oscillations or wave propagation. This work should facilitate research on more complex natural oscillations; in this model system the genetic clock produces synchronized flashes of light but similar genetic switching could trigger events relating to insulin secretion and circadian rhythms, for instance. A defining focus of synthetic biology is the engineering of genetic circuits with predictive functionality in living cells. Here, a decade after the first synthesized genetic toggle switch and oscillator, an engineered gene network with global intercellular coupling is designed that is capable of generating synchronized oscillations in a growing population of cells.

Synthetic gene networks can be constructed to emulate digital circuits and devices, giving one the ability to program and design cells with some of the principles of modern computing, such as counting. A cellular counter would enable complex synthetic programming and a variety of biotechnology applications. Here, we report two complementary synthetic genetic counters in Escherichia coli that can count up to three induction events: the first, a riboregulated transcriptional cascade, and the second, a recombinase-based cascade of memory units. These modular devices permit counting of varied user-defined inputs over a range of frequencies and can be expanded to count higher numbers.

Fruit-specific overexpression of a pair of snapdragon transcription factors produces tomatoes that uniformly accumulate anthocyanins at levels unprecedented for metabolic engineering. When included as a dietary supplement, the purple tomatoes increase the life spans of tumorigenic p53 knockout mice. Dietary consumption of anthocyanins, a class of pigments produced by higher plants, has been associated with protection against a broad range of human diseases. However, anthocyanin levels in the most commonly eaten fruits and vegetables may be inadequate to confer optimal benefits. When we expressed two transcription factors from snapdragon in tomato, the fruit of the plants accumulated anthocyanins at levels substantially higher than previously reported for efforts to engineer anthocyanin accumulation in tomato and at concentrations comparable to the anthocyanin levels found in blackberries and blueberries. Expression of the two transgenes enhanced the hydrophilic antioxidant capacity of tomato fruit threefold and resulted in fruit with intense purple coloration in both peel and flesh. In a pilot test, cancer-susceptible Trp53 −/− mice fed a diet supplemented with the high-anthocyanin tomatoes showed a significant extension of life span.