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Proceedings of the National Academy of... Jul 2015There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the... (Review)
Review
There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits.
Topics: Animals; Cloning, Organism; Genetic Diseases, Inborn; Genetic Therapy; Genotype; Humans; Phylogeny; Social Values
PubMed: 26195738
DOI: 10.1073/pnas.1501798112 -
Nature Jan 2012Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The... (Review)
Review
Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The dynamics are complex, with highly variable patterns of genetic diversity and resulting clonal architecture. Therapeutic intervention may destroy cancer clones and erode their habitats, but it can also inadvertently provide a potent selective pressure for the expansion of resistant variants. The inherently Darwinian character of cancer is the primary reason for this therapeutic failure, but it may also hold the key to more effective control.
Topics: Animals; Clonal Evolution; Clone Cells; Genomics; Humans; Mutation; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 22258609
DOI: 10.1038/nature10762 -
International Journal of Molecular... Mar 2020Somatic cell nuclear transfer (SCNT) has been an area of interest in the field of stem cell research and regenerative medicine for the past 20 years. The main biological... (Review)
Review
Somatic cell nuclear transfer (SCNT) has been an area of interest in the field of stem cell research and regenerative medicine for the past 20 years. The main biological goal of SCNT is to reverse the differentiated state of a somatic cell, for the purpose of creating blastocysts from which embryonic stem cells (ESCs) can be derived for therapeutic cloning, or for the purpose of reproductive cloning. However, the consensus is that the low efficiency in creating normal viable offspring in animals by SCNT (1-5%) and the high number of abnormalities seen in these cloned animals is due to epigenetic reprogramming failure. In this review we provide an overview of the current literature on SCNT, focusing on protocol development, which includes early SCNT protocol deficiencies and optimizations along with donor cell type and cell cycle synchrony; epigenetic reprogramming in SCNT; current protocol optimizations such as nuclear reprogramming strategies that can be applied to improve epigenetic reprogramming by SCNT; applications of SCNT; the ethical and legal implications of SCNT in humans; and specific lessons learned for establishing an optimized SCNT protocol using a mouse model.
Topics: Animals; Blastocyst; Cell Differentiation; Cellular Reprogramming; Cloning, Organism; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Epigenomics; Eye Enucleation; Humans; Nuclear Transfer Techniques; Oocytes
PubMed: 32230814
DOI: 10.3390/ijms21072314 -
Nature Nov 2020Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk...
Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.
Topics: Cell Separation; Clone Cells; DNA Mutational Analysis; Humans; Immunophenotyping; Mutation; Myeloproliferative Disorders; Single-Cell Analysis
PubMed: 33116311
DOI: 10.1038/s41586-020-2864-x -
La Clinica Terapeutica 2023This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal... (Review)
Review
This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal implications. The exposition commences with a succinct historical and contextual overview of human cloning, segueing into an in-depth exploration of its biological intri-cacies. Central to this biological scrutiny is a comprehensive analysis of somatic cell nuclear transfer (SCNT) and its assorted iterations. The accomplishments and discoveries in cloning technology, such as successful animal cloning operations and advances in the efficiency and viability of cloned embryos, are reviewed. Future improvements, such as reprogramming procedures and gene editing technology, are also discussed. The discourse extends to ethical quandaries intrinsic to human cloning, entailing an extensive contemplation of values such as human dignity, autonomy, and safety. Furthermore, the ramifications of human cloning on a societal plane are subjected to scrutiny, with a dedicated emphasis on ramifications encompassing personal identity, kinship connections, and the fundamental notion of maternity. Culminating the analysis is a reiteration of the imperative to develop and govern human cloning technology judiciously and conscientiously. Finally, it discusses several ethical and practical issues, such as safety concerns, the possibility of exploitation, and the erosion of human dignity, and emphasizes the significance of carefully considering these issues.
Topics: Animals; Female; Humans; Pregnancy; Cloning, Organism; Nuclear Transfer Techniques; Self Concept; Biology
PubMed: 37994769
DOI: 10.7417/CT.2023.2492 -
International Journal of Molecular... Nov 2022Thus far, nearly 25 mammalian species have been cloned by intra- or interspecies somatic cell nuclear transfer (SCNT) [...].
Thus far, nearly 25 mammalian species have been cloned by intra- or interspecies somatic cell nuclear transfer (SCNT) [...].
Topics: Animals; Cloning, Organism; Nuclear Transfer Techniques; Mammals; Cloning, Molecular
PubMed: 36430264
DOI: 10.3390/ijms232213786 -
Journal of Veterinary Science Sep 2018Dogs serve human society in various ways by working at tasks that are based on their superior olfactory sensitivity. However, it has been reported that only about half... (Review)
Review
Dogs serve human society in various ways by working at tasks that are based on their superior olfactory sensitivity. However, it has been reported that only about half of all trained dogs may qualify as working dogs through conventional breeding management because proper temperament and health are needed in addition to their innate scent detection ability. To overcome this low efficiency of breeding qualified working dogs, and to reduce the enormous costs of maintaining unqualified dogs, somatic cell nuclear transfer has been applied in the propagation of working dogs. Herein, we review the history of cloning working dogs and evaluate the health development, temperaments, and behavioral similarities among the cloned dogs. We also discuss concerns about dog cloning including those related to birth defects, lifespan, and cloning efficiency.
Topics: Animals; Behavior, Animal; Cloning, Organism; Dogs; Nuclear Transfer Techniques; Temperament
PubMed: 29929355
DOI: 10.4142/jvs.2018.19.5.585 -
Molecular Therapy : the Journal of the... May 2003
Topics: Animals; Animals, Genetically Modified; Biotechnology; Cloning, Organism; Sheep
PubMed: 12755157
DOI: 10.1016/s1525-0016(03)00109-6 -
Journal of Assisted Reproduction and... Aug 2001
Topics: Cloning, Organism; Embryo, Mammalian; Ethics; Humans; Research; Stem Cells
PubMed: 11599469
DOI: 10.1023/a:1016699024033 -
Annual Review of Animal Biosciences Feb 2024Cloning as it relates to the animal kingdom generally refers to the production of genetically identical individuals. Because cloning is increasingly the subject of... (Review)
Review
Cloning as it relates to the animal kingdom generally refers to the production of genetically identical individuals. Because cloning is increasingly the subject of renewed attention as a tool for rescuing endangered or extinct species, it seems timely to dissect the role of the numerous reproductive techniques encompassed by this term in animal species conservation. Although cloning is typically associated with somatic cell nuclear transfer, the recent advent of additional techniques that allow genome replication without genetic recombination demands that the use of induced pluripotent stem cells to generate gametes or embryos, as well as older methods such as embryo splitting, all be included in this discussion. Additionally, the phenomenon of natural cloning (e.g., a subset of fish, birds, invertebrates, and reptilian species that reproduce via parthenogenesis) must also be pointed out. Beyond the biology of these techniques are practical considerations and the ethics of using cloning and associated procedures in endangered or extinct species. All of these must be examined in concert to determine whether cloning has a place in species conservation. Therefore, we synthesize progress in cloning and associated techniques and dissect the practical and ethical aspects of these methods as they pertain to endangered species conservation.
Topics: Animals; Endangered Species; Cloning, Organism; Nuclear Transfer Techniques; Fishes; Cloning, Molecular
PubMed: 37988633
DOI: 10.1146/annurev-animal-071423-093523