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Functional Genomics

Overview

Genomics is the branch of genetics that studies organisms in terms of their genomes or full DNA sequences. Functional genomics is the branch of genomics that determines the biological function of genes and their products.

By studying the expression of genes inside a cell, scientists can get a picture of gene activity and, indirectly, of the physiological function the cell performs. In functional genomics, these gene expression studies are carried out on a genome-wide scale. Scientists who study gene expression will usually analyse an organism's messenger RNAs. Messenger RNAs are the transcripts from active genes inside a cell. An animal's genome is probably capable of producing about 30,000 different messenger RNAs, so special tools are needed to study them all at once (see below Microarrays).

The term 'functional genomics' is also used to describe high-throughput gene function studies. Researchers would typically use cell culture model systems to study the functional importance of particular molecules identified in genomics studies. It is important to know what role is played by a newly discovered gene, in order to develop agricultural biotechnology applications related to that gene.

By conducting functional genomics studies on dairy cows, the Dairy CRC hopes to discover which genes affect an animal's characteristics or traits that are useful to the farmer. Genes of interest to the Dairy CRC include those that impact on lactation, disease resistance and fertility, and genes associated with production of the microcomponents in milk that have valuable, health-giving properties (see Bioactives).

Technologies

Experimental models have to closely simulate what happens in the real world. The Dairy CRC has set up a model system that closely resembles the functioning mammary gland in the cow - a mammary epithelial cell culture system (see right). These cells produce proteins in a similar way that mammary glands produce milk. The Dairy CRC uses a wide range of biological resources to carry out research on the lactation systems of different mammals. These include mammary tissue samples from mice, dairy cattle, sheep, seals and wallabies, and samples of embryos. The Dairy CRC uses several different approaches to study gene expression on a genome-wide scale, including microarrays. The international Bovine Genome Sequencing Project aims to completely sequence the bovine genome by 2005. This will provide scientists with a further tool for studying the functional genomics of the dairy cow.

 Microarrays

A microarray is an important tool for scientists studying the expression of particular genes. A microarray is a "printout" of a large number of DNA probes for individual genes on a solid surface (see right). Tens of thousands of probe spots can generally be printed on a surface the size of a microscope slide. In order to conduct a microarray experiment, researchers then extract the messenger RNAs from the cells of interest and label them so they can be detected by a laser or other imaging application. The labelled messenger RNAs are allowed to bind to the spots on the microarray and researchers can then determine the amount of each messenger RNA that has bound to each probe spot. This data is used to build a picture about the genome-wide changes in gene expression that accompany cellular, physiological or developmental changes in an organism.

Advantages

  • By researching functional genomics of the dairy cow, the Dairy CRC will find genes associated with particular characteristics in dairy cows sought after by farmers.
  • Discovery of these genes will speed up the rate of 'genetic gain" in the Australian dairy herd, that is, the cows will have more of the genes associated with the traits farmers want.
  • The Dairy CRC's study of mammary tissue samples from a range of species (cow, wallaby, seal, mouse and sheep) combined with the use of microarray technologies is a powerful way to tackle the discovery of genes and their functions.
  • Provisional patents of key genes, which protect Dairy CRC's intellectual property may be valuable (see Patenting inventions) for investors.

Challenges

Choosing which technical platform is most appropriate to study a particular function is difficult. Scientists in the Dairy CRC use a variety of the available technologies.

  • The technologies are very expensive to use.
  • Sophisticated bioinformatics is essential to produce meaningful results (see Bioinformatics).
  • Choosing which genes to focus on with gene function studies is challenging. The Dairy CRC must focus on genes that will have commercial applications in the dairy industry.
  • The technology that the Dairy CRC develops has to be safe, effective and meet quality assurance standards.

Applications in the Dairy CRC

Milk Production
The Dairy CRC is investigating genes associated with particular characteristics or traits in the dairy cow, such as the volume of milk a cow can produce or the likely length of its lactation period. These traits are of great importance to farmers because if a cow can produce a high volume of milk or have a long lactation, it will be a more profitable animal.

Bioactives
The Dairy CRC is also interested in genes associated specific microcomponents found in milk that have valuable, health-giving properties (see Bioactives).

Animal health and welfare
The Dairy CRC is also investigating genes associated with susceptibility or resistance to diseases including mastitis, an infection of the udder caused by bacteria. Mastitis causes a $140 million loss each year to the Australian dairy industry. This disease reduces milk production, alters milk quality and costs Australian dairy farmers $120-$150 per cow to treat.

Molecular studies of cow embryos
Functional genomics is also used by the Dairy CRC team to uncover some of the factors that may affect the viability of cattle embryos. A Dairy CRC team at CSIRO Livestock Industries studies the genes and proteins expressed in cattle embryos in order to arrive at new clues for what determines embryos' ability to develop.

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