Animal Biotechnology Science-Based Concerns (2002) / Chapter Skim
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2. Applications of Biotechnology Techniques
2. Applications of Biotechnology Techniques
Pages 34-50
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From page 34... ...
Subsequent chapters will discuss how the technical issues can directly affect human health, the food supply, animal welfare, and the environment. INTRODUCTION OF NOVEL GENES A number of methods are presently employed for genetic engineering of various animal species.
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From page 35... ...
manipulation of cultured somatic cells, whose nuclei then can be transferred into enucleated oocytes and thereby provide the genetic information required to produce a whole animal. The last two methods have the advantage of allowing cells containing the modification of interest to be selected prior to undertaking the expensive and lengthy process of generating animals.
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From page 36... ...
No active transposons of these types have been observed in mammals, although the human genome contains thousands of copies of a DNA sequence related to the mariner transposon of Drosophila (Lander et al., 2001) , suggesting that there might have been active elements in our recent evolutionary history.
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From page 37... ...
DIRECTED GENETIC MANIPULATION Another goal of transgenic technology is the creation of engineered animals that lack specific genes (knockout) , or have these genes replaced by one that has been engineered in a specific way (knockin; see Box 2.1~.
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From page 38... ...
Because the process is so inefficient, very large numbers of transfected cells must be screened, making the use of cultured cells essential, since it would be impracticable to screen large numbers of progeny from microinjected eggs. The galactosyl transferase-knockout pigs discussed above were generated from cultured fetal fibroblasts manipulated in this way.
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From page 39... ...
Dolly represented the most recent advance in genetic technology the production of multiple individuals nearly genetically identical to an adult animal. In this technique, somatic cells Dom an appropriate tissue are grown in culture and their nuclei are injected into enucleated oocytes obtained from another individual of the same or a closely related species.
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From page 40... ...
However, even with this existing low efficiency, there are many potential applications for reproducing highly desired genotypes, including rare or endangered species, household pets, elite sires or dams, breeds with desirable production traits but low fertility, sterile animals such as castrates and mules, or transgenic animals that have high value and for which rapid propagation is desirable. Another important application of this technology is in the dissemination of germplasm as embryos and consequent reduction of the associated risk of disease spread (Prather et al., 1999~.
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From page 41... ...
While these effects do not directly affect the safety or utility of those animals that are eventually used, they do introduce considerable inefficiency into the system A further problem with obtaining correct expression of an introduced transgene is that introduced genes are subjected to silencing by processes including methylation of C residues at CpG dinucleotides, which frequently are found in chromosomal regions important in the regulation of gene expression. Methylation is a major mechanism for turning off the expression of inappropriate genes in somatic cells.
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From page 42... ...
Such vectors promise to yield more efficient and reliable means of generating transgenic animals of many species. Similar vector systems based on the distantly related feline immunodeficiency virus (FIV)
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From page 43... ...
the integration site can be activated, including promoter and enhancer insertion, as well as gene fusion and introduction of elements that stabilize messenger RNA (Rosenberg and Jolicoeur, 1997~. Indeed, alteration of expression of genes at genome sites far removed from a transgene has been reported in cell lines, apparently due to altered methylation (Muller et al., 2001~.
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From page 44... ...
Pigs that are engineered by knockout of this gene would, therefore, have the potential to transmit viruses, such as influenza, much more readily to human handlers. A related concern is that human cell-surface proteins introduced into animal species as transgenes could render those animals susceptible to human viruses, increasing their risk of disease and providing alternative hosts for the spread of human disease.
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From page 45... ...
Inadvertent introduction of such sequences into the germline of transgenic animals not only has the potential for creating unintended genetic damage, but also can contribute by recombination to the generation of novel infectious viruses. A well-known example is the inadvertent generation of replication-competent MLV's containing multiple such recombinants during the growth of a vector containing a globin gene (Purcell et al., 19964.
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From page 46... ...
Generation of a replicating virus could occur in the absence of exogenous infection, since many species contain endogenous retroviruses in their genomes that could serve as agents of this kind of mobilization. For example, in cats carrying murine leukemia virus-based vector constructs, the introduced genes could be mobilized to other cats (or, at least theoretically, to their human hosts)
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From page 47... ...
This virus apparently arose as the result of a single, very rare event, but subsequently has been spread worldwide and has become a source of considerable economic loss to poultry breeders (Venugopal, 1999~. ISSUES RELATED TO SOMATIC CELL NUCLEAR TRANSFER TECHNOLOGY The generation of animals using nuclear transfer from somatic cells has received a great deal of attention recently, and it is clear that this technology is 5
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From page 48... ...
, the lack of appropriate-length telomeres might be expected to reduce the lifespan of the newly generated offspring or their progeny, but, surprisingly, telomere length (and lifespan of cultured cells) are restored to normal values following generation of cattle by somatic cell nuclear transfer (Bests et al., 2001)
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From page 49... ...
The consequences of the failure of immunorecognition is illustrated by the deadly epidemics of diseases such as measles spread by initial contact between Europeans and isolated New World populations that lacked adequate MHC diversity. Not only could enhanced susceptibility create significant risk for the spread of"new" infectious diseases in "monocultures" of cloned or highly inbred animal populations; it also could create new reservoirs for spread of zoonotic infections like new strains of influenza to humans.
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From page 50... ...
50 ANIMAL BIOTECHNOLOGY: SCIENCE-BASED CONCERNS the use of unnecessary genes in constructs used for generation of engineered animals, the use of vectors with the potential to be mobilized or to otherwise contribute sequences to related environmental organisms, and the effects of the technology on the welfare of the engineered animals themselves.
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