The agricultural holy grail

It took at least 8000 years create the modern world's domestic cattle breeds from aurochs, (Bos taurus ssp primigenius), the wild Eurasian ancestors of dairy and beef cattle.

Even with advanced conventional breeding and reproduction techniques, including the use of DNA markers to track elite alleles of genes for desirable production traits, artificial insemination and embro transplantation, it still takes at least five years from conception to produce a new bull calf, rear it to sexual maturity and progeny-test its offspring.

Dr Jon Hill, head of Livestock Industries' Advanced Breeding Technologies program in Armidale, NSW, believes a combination of genomics and advanced technologies could compress that entire cycle into just a few weeks, and have the first superior new calves on the ground in little more than a year.

Molecular breeding and selection tools, including comparative genomics, marker-assisted selection, in situ gene-silencing or manipulation, transgenics and in vitro fertilisation with embryo-derived gametes - a powerful technique that promises to condense large-animal breeding cycles into mere months - will also fast-track breed improvement in the wool, fat lamb, pig and poultry industries.

Australia's representative on the Bovine Genome Sequencing Project, CSIRO Livestock Industries' molecular geneticist Dr Ross Tellam, says the revolution will be underpinned by the BGSP, and in its linkages to the Human Genome Project.

The approach is through comparative genomics. As researchers explore the function of the 25,000-odd human genes, cattle geneticists will cross reference the data with the cattle genome project to help pinpoint genes associated with desirable traits in cattle. Cattle and sheep geneticists will also be able draw upon the wealth of genomic data from the mouse, dog and other mammals.

Cattle genome sequence

Sequencing of the cattle genome began three years ago and is now virtually complete, with anticipated release in the next few months. Baylor College of Medicine's Human Genome Sequencing facility in Texas headed the sequencing effort, made possible by an international consortium of agencies and scientists. The Vancouver Human Genome Sequencing Center has also played a role in sequencing a select group of genes.

Australian researchers were not directly involved in the highly automated sequencing phase, but will be involved in analysing the data. They were prominent in defining a strategy and helping to organise and manage the project.

The BGSP consortium, a large international group of agencies including the NHGRI (USA), CSIRO Livestock Industries (Australia), the US Department of Agriculture, the State of Texas, Genome Canada, New Zealand's Agritech Investments Ltd, Dairy Insight Inc and Agresearch Ltd, the Kleberg Foundation (USA), and the US, Texas and South Dakota Beef Councils.

Geneticists will employ the cattle genome as a template to highlight genetic variation within and between cattle breeds, and between cattle and other mammals. Most variation occurs as single-nucleotide polymorphisms (SNPs).

"One of the major outcomes of the project so far has been the identification of around two million SNPs," Tellam says. "A subset of these has been used to create a microchip featuring 10,000 SNPs, and another containing 30,000 SNPs is being developed.

"These chips are very valuable as they allow identification of associations between specific genetic polymorphisms, SNP, and production traits of interest." The genetic markers can then be used in marker assisted selection programs to enrich desirable traits within a herd.

"We already know that there are large differences in SNP patterns between Bos taurus and Bos indicus breeds and that these probably underpin the different characteristics of these breeds.

"Knowledge of gene function is also important. We already have a very good knowledge of the repertoire of bovine genes, and we can now use gene microarrays to interrogate the collective activity of tens of thousands of genes simultaneously, to identify those involved in important cow functions like lactation, reproduction, muscling, growth rate and disease resistance.

"Once we've identified these genes, we can modulate them in an acceptable manner to improve productivity." Tellam says one of the Holy Grails of cattle genomics is to improve energy efficiency.

"The ability to convert low-energy grass into high-energy muscle in beef breeds has a strong genetic component," he says. "A combination of functional genomics with SNP association studies may identify the crucial genes. Selection for these genes may help to decrease the environmental footprint of the livestock industry whilst maintaining productivity.

"This is just the beginning of a revolution in the way we produce our animals and food. The bovine and ovine sequences will have a marked impact on the livestock industry over the next 25 years.

"There is enormous potential to improve the profitability and sustainability of the grazing industries while addressing some of the key environmental and animal ethics issues."

Bioinformatics

CSIRO Livestock Industries bioinformatician Dr Brian Dalrymple set up a bioinformatics group in the division several years ago, to use data from the Bovine Genome Project.

"As the genome project nears completion my group is moving away from sequence-based bioinformatics to study gene interactions, and explore gene networks involved in specific cell and tissue functions," he says.

His team and its collaborators have analysed a large gene-expression data set for the longissimum dorsi muscle in beef cattle - the two long muscles flanking the spine that yield tender eye fillets.

From this data, generated in a number of projects primarily undertaken in the Beef Quality CRC, they are developing a model of interactions between genes and proteins that influence the muscle's development, structure and function.

"We're trying to develop a model that will tell us what will happen if we knock out a particular gene, and to determine the different phenotypic effects of alleles of the same gene. We could then predict what will happen when we combine particular alleles of a number of genes that influence traits like tenderness, for example.

"We can already identify cattle carrying known DNA markers for tenderness, but we don't do as well as we could predicting the tenderness score, because we don't know how the various genes interact."

"Once we have a complete set of genes that influence tenderness, we want to know that, if we have an animal with this particular genotype, and we feed it on this type of pasture, it will consistently produce meat of a particular standard of tenderness and marbling. But we're probably still years away from being able to do this."

The first generation of GeneSTAR DNA markers for tenderness and marbling, developed by Dr Bill Barendse's research group, is already transforming beef production, returning value to producers and delivering better-quality beef to consumers. A second generation of markers - the first based on SNPs - is now on its way from laboratory to industry.