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Amazing ambitions
Published in Brendan Curran, A Terrible Beauty is Born, 2020
Chapter 3 made the point that the incredibly long DNA molecules storing all the genes required for making a human being are wrapped up in our cells into chromosomes. We normally have 46 of them, each one with specialised sequences to ensure that the chromosome is properly replicated every time a cell divides. In 1997, a group of scientists succeeded in constructing an artificial chromosome in cultured human cells. They will now be able to assemble complex genetic programmes consisting of multiple genes, each regulated by control switches primed for activation in certain tissues or when a certain drug is taken. Once perfected, artificial chromosomes will allow complex genetic systems, perhaps even including intelligence, to be manipulated should we so desire. There are more ethical problems on the horizon.
Approach to women with a previous child with a genetic disorder
Published in Minakshi Rohilla, Recurrent Pregnancy Loss and Adverse Natal Outcomes, 2020
This test identifies common trisomies 13, 18, 21, and X/Y and nine other common microdeletion syndromes. A bacterial artificial chromosome is a sequence of DNA that has been incorporated into a bacterium to allow a large amount of the sequence of interest to be manufactured. Bacterial artificial chromosomes derived from each chromosomal region of interest are then immobilized on a bead, which then has three fluorochromes attached for quantifying the reaction. The sample DNA is then added and analyzed. It uses two probes per chromosome arm and three for each acrocentric chromosome and has been shown to be an accurate method of identifying trisomies [6]. As culture failure is not an issue, this test can be used on products of conception. Terminal duplication and deletion have a lower overall pickup rate and may not be suitable for this analysis.
Pathology, Neurobiology, and Animal Models of Alzheimer’s Disease
Published in Zaven S. Khachaturian, Teresa S. Radebaugh, Alzheimer’s Disease, 2019
Juan C. Troncoso, Barbara J. Crain, Sangram S. Sisodia, Donald L. Price
Because it has been difficult to overexpress APP using conventional transgenic technologies, Lamb and co-workers95 recently used yeast artificial chromosome-embryonic stem (YAC-ES) technologies to express human APP in mice. A 650-kb YAC containing the entire unrearranged 400-kb APP gene was transferred by lipid-mediated transfection into ES cells. Cells that expressed human APP were then introduced into mouse blastocytes to generate chimeric mice. Subsequent breeding efforts resulted in mice that harbor human sequences in the germline. Levels of transgene expression in the brain and peripheral tissues of these animals are approximately equivalent to the mouse endogenous APP level. These mice are still too young to be expected to develop Aβ deposits. However, these animals will be valuable for breeding to the apoE transgenic mice to test the hypothesis that multiple factors are necessary to produce neuropathological abnormalities.
From leptin to lasers: the past and present of mouse models of obesity
Published in Expert Opinion on Drug Discovery, 2021
Joshua R. Barton, Adam E. Snook, Scott A. Waldman
Monogenic mouse models have been invaluable for elucidating the molecular mechanisms underlying obesity and metabolic disease. By 2015, mouse models of 221 distinct genes had been studied for obesity-related phenotypes [144]. This list is continually expanding, as are the tools that allow researchers to interrogate the mechanisms behind obesity. Large-scale projects like The GENSAT Project at Rockefeller University have developed hundreds of Bacterial Artificial Chromosome (BAC)-driven GFP and Cre mouse lines that have been used in over 1000 publications [145]. Multi-institutional, international projects have developed suites of neuron specific Cre-drivers and toolboxes of transgenic mice with Cre-dependent optogenetic channels for dissecting the neural circuits that underlie mammalian behavior [146,147]. These herculean efforts provide obesity researchers with thousands of combinations of transgenic mice that can study the interactions between appetitive pathways. While individual circuits are being rigorously mapped and stimulated, discovery of how these pathways work in concert to evoke feeding responses is a crucial next step to precisely modulating satiety in human obesity.
Ethical Framework for Next-Generation Genome and Epigenome Editing
Published in The American Journal of Bioethics, 2020
Kyoko Akatsuka, Mitsuru Sasaki-Honda, Tsutomu Sawai
Another therapeutic strategy for DMD is the application of a human artificial chromosome (HAC), which is a gene transfer vector utilizing the replication function of human chromosomes. The introduction of HAC carrying a normal dystrophin gene can supply adequate gene expression in the diseased cells (Kazuki et al. 2010). Because HAC is artificial, unlike mitochondrial DNA in MRT, it is “transferring” genetic material that is not an individual origin. Other DNA-based vectors that are widely supposed for gene delivery in gene therapy (Adeno-associated virus vector, Sendai virus vector, etc.) can also be categorized as “transferring” artificial genetic materials, but inheritance of these materials to future generations through germline systems should be considered (Wang et al. 2020). DNA-based delivery systems involve the introduction of artificial genetic materials that are not included in the original 46 chromosomes, and in some cases the materials should remain permanently to sustain their therapeutic effects. These cases require reconsidering the dimension “mechanics,” which relates to the introduction of novel genetic materials.
Strategies for recombinant production of antimicrobial peptides with pharmacological potential
Published in Expert Review of Clinical Pharmacology, 2020
Kamila Botelho Sampaio de Oliveira, Michel Lopes Leite, Gisele Regina Rodrigues, Harry Morales Duque, Rosiane Andrade da Costa, Victor Albuquerque Cunha, Lorena Sousa de Loiola Costa, Nicolau Brito da Cunha, Octavio Luiz Franco, Simoni Campos Dias
Heterologous expression of NRPS usually involves a cosmid or fosmid library approach, which allows genes up to 40kb to be cloned. That could be a limiting factor since some NRPS gene clusters sometimes achieve up to 100kb [264]. Other strategies such as BAC (bacterial artificial chromosome) derived libraries are able to capture and clone inserts that are twofold larger [265]. The TAR system could be used to capture larger gene clusters directly from eDNA and express them in S. cerevisiae [266,267].