Introduction to Transgenesis

 From Gene to Function
The sequencing of the human genome has had a major impact on our understanding of our genetic make-up. Since its launch in 1990, the Human Genome Project has worked towards the goal of sequencing every gene in the human genome and mapping them to their precise chromosomal locations. In 2001, draft sequences of the full human genome were published and in 2004 were refined to reveal that there are between 20 000 and 25 000 protein-encoding human genes.1,2 It is now vital that we fully address the next big challenge – to identify the function of these genes in both health and disease. A number of technologies are currently used to analyse mammalian gene function, including the techniques that will be the focus of this chapter – transgenesis technologies.
This chapter will outline the transgenic techniques that are currently used to modify the genome in order to extend our understanding of the in vivo function of these genes in normal development and physiology, and also in pathogenesis.

Transgenesis is a general term which covers several ways of modifying the genome of intact organisms, for example, it is possible to eliminate a gene of interest or introduce extra pieces of DNA (overexpress) in a whole organism or a specific tissue. Transgenesis can be carried out in
numerous organisms, including plants, the fruit fly (Drosophila), worm (Caenorabditis elegans), frog (Xenopus), zebrafish, large mammals including sheep and small mammals such as the rat and mouse. Each of these model organisms is valuable in its own right; the fruit fly and the worm have been used extensively to provide information regarding the basic functional processes of organisms such as cell proliferation, metabolic pathways and developmental processes. The zebrafish is particularly suited to use in studies to elucidate vertebrate gene function and large mammals have even been used as ‘bio incubators’ to produce recombinant proteins. Although historically the rat has been used in many physiological experiments, the ability to modify its genome is much more limited than in the mouse. Subsequently, it is the mouse that has become by far the most popular organism in which to study mammalian gene function and in particular human disease.
This chapter will outline the most commonly used transgenic technologies applied to the mouse genome, including overexpression transgenesis, gene targeting and conditional gene targeting. In addition, it will outline how we determine in vivo function in the mice that are generated by these transgenic techniques and, finally, we address some of the ethical issues which must be considered when using animals as a model system for research.

مواضيع ذات صلة

الإضعاف :التوقف المبكر للاستنساخ (Attenuation: the premature termination of transcription)

كابح التربتوفان tryptophan repressor

Gel Electrophoresis Assay of Eukaryotic Replication Origins

Constancy of the E. coli DNA Elongation Rate

Bidirectional Replication from E. coli Origins

أوبرون اللاكتوز lac operon

اكتشاف الأوبرون

مثبطات تخليق البروتين .... وسيلة للعلاج

تحوير سلاسل الأحماض الأمينية الجانبية للبروتين (Amino acids side chains modifications)

تحوير التركيب البروتيني ثلاثي الأبعاد (Three dimensional structure modifications)

Error and Damage Correction

فروقات بدء الترجمة بين بدائية وحقيقية النواة