Gene mapping in r-bearing animals: genetic maps and comparative gene mapping
Oleg L. Serov 1 and Nikolay B. Rubtsov
Institute of Cytology and Genetics, Academy of Sciences of Russia, Siberian Department, Novosibirsk 630090, Russia
(файл gene mapping of r-animals.pdf)
Over the last decade, there has been marked progress in gene mapping in man and some animals. Advances in gene mapping have also touched fur-bearing animals: the genetic map of mink consists of 74 genes marking all chromosomes, except the Y, and the fox map contains 35 genes marking 15 of 16 autosomes and the X chromosome. However, until recently there has been little information about the structure of fur colour coding genes and their chromosomal localizations in mink and fox. Comparisons of the mink gene map with those of man and other mammals have revealed the presence of giant conserved gene regions, presumably derived from a common ancestral genome. The fox genome contains fewer such regions. The existence of conserved regions of syntenic genes in phylogenetically remote species allows comparative mapping to be used as a powerful tool for a targeted search for the location of important genes in fur-bearing animals.
During the last five years, advances in livestock genome mapping have been remarkable. Species-specific genetic maps exist for cattle, sheep, pigs, fowls and horses, with marker intervals of 5-20 cM. These maps have been essential for the identification of genes and genetic markers associated with economically important traits in livestock, thereby having a significant impact on world-wide livestock production. In addition, many aspects of livestock genome projects will contribute to human genetic research.
Nucleic Acid Therapeutics: Current Targets For Antisense Oligonucleotides And Ribozymes
Pramod K Yadava
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
(файл nucleic acid therapeutics.pdf)
Nucleic acids are becoming increasingly important as therapeutic molecules mainly for the ease with which specificity for a vast range of targets of these drugs is achieved. Yet the dose rates of several mg/kg are not easy to provide. Reform of drug policy has been suggested earlier to facilitate newer therapeutic strategies to be put to use.With the current technology, each mg of the unmodified oligonucleotide would cost US$ 20. That means someone with 50 kg of body weight requiring 50 mg would require to pay ca US$1000/- per dose. That is where targeted delivery systems emerge as a possible hope for minimizing on the dose rates while new technology for synthesis for economical production of these drugs would remain welcome. The suspected toxicity and non-specificity associated with certain modifications need to be scrutinized. Studies on potential side effects and frequency of insertion of the administered oligonucleotides in recipient cell's genome must remain under vigilance. In antiviral and anticancer applications, it will be necessary to establish regimen that ensures complete cure to avoid resurgence on withdrawal of the drugs. Most of the current data show good but partial elimination of viral or cancer targets.
Removal of specific DNA regions from transgenes - a necessary step to improve the precisionof transgene technology?
Leeds Institute for Plant Biotechnology and Agriculture (LIBA), Centre for Plant Science, The University of Leeds, Leeds LS2 9JT, UK
Transgene technology offers significant advantages for modern agriculture, provided we will be able to define the most beneficial applications. Although various social, political and financial interests in the developed and the developing world will make such a choice rather difficult, a common requirement for the successful exploitation of transgene technology will be its reliability. An important aspect for this reliability is the composition of the transgene. The insertion of a recombinant DNA construct into a plant genome can produce transgenes of relatively complex character, which include direct or inverted, full-size or partial repeats of the recombinant DNA. Currently, we cannot control the position in the plant genome into which a transgene finally integrates, and we have little influence on how the transgenic region looks following its integration. There is growing evidence that a complex integration structure of a transgene or the presence of bacterial DNA can have an adverse affect on the long-term stability of transgene expression. Moreover, most transgenic constructs contain genetic regions, such as selectable marker genes or bacterial DNA regions that were required for amplification, transfer or selection of the transgenic vector but that are no longer needed after transformants have been selected. There has been particular concern about the potential transmission of antibiotic and herbicide resistance genes to other organisms. As a contribution to improving transgene reliability and public acceptance alike, it would therefore be desirable to remove specific regions from transgenes following their integration into the plant genome. This article discusses how site-specific and homologous recombination systems can be used to achieve this goal.
Plant gene therapy: crop varietal improvement through the use of chimaeric RNA/DNA oligonucleotide-directed gene targeting
Gregory D. May
Plant Biology Division, Samuel Roberts Noble Foundation,
Ardmore, OK 73402, USA
Eric B. Kmiec
Department of Biology, University of Delaware,
Newark, DE 19716, USA
(файл plant gene therapy.pdf)
Chimaeric RNA/DNA oligonucleotides are synthetic molecules comprised of DNA and RNA bases that assume a self-complementary double hairpin conformation. These molecules have been shown to direct site-specific base changes in plant and animal cells, while not introducing foreign DNA into the genome. Progeny from modified plants derived through the use of this technology have been shown to inherit gene conversions in a Mendelian fashion. Little is known about the mechanism by which these molecules facilitate targeted base changes in plants. Here we discuss strategies to (1) gain a better fundamental understanding of the conversion process in plants, (2) optimise targeting molecule design, and (3) increase efficiency of the conversion process by using a high-throughput assay system. This plant-based cell-free extract system will also assist in the elucidation of gene targeting and plant DNA repair mechanisms. In addition, we discuss the state-of-the-art in oligonucleotide-directed targeted mutagenesis and its current limitations, its potential impact on fundamental plant biology and crop varietal improvement, and where improved varieties, derived through the use of this technology, fit under the current definition of genetically modified organisms.