The designer dairy cow

Comparative genomics is helping speed up the identification of genes for desirable production traits in livestock, Graeme O'Neill reports.

It will be very difficult to develop genetically engineered livestock species until new techniques make it possible to insert transgenes at specific chromosomal sites in multiple animals, a leading Dutch livestock researcher told the Horizons in Livestock Science conference on the Gold Coast last month.

Prof Johan van Arendonk, chair of the animal breeding and genetics group at Wageningen University, told the conference that male and female animals need transgenes to be inserted at corresponding loci to ensure homozygous inheritance and expression.

Van Arendonk said the inability of molecular geneticists to perform site-specific transgene insertion is seriously hindering the development of transgenic breeds with desirable new traits. The non-transgenic alternative was to use marker-assisted selection to exploit natural variation. But this will depend on applying genomic data to predict breeding values for specific traits.

He said the goal was to breed animals with superior performance, but this did not mean breeding towards a fixed target -- the goals would depend on the production environment, market preferences, and economic conditions.

For example, only three or four major companies now supply chicks to poultry farms around the world. Requirements vary according to whether producers are large- or small-scale, and employ cage, barn or free-range production systems.

Healthier breeds

Van Arendonk said that as the world's population increases rapidly creating demand for more animal protein, urbanisation and a shift towards renewable biofuels are reducing the area of land available for animal production.

Food quality is increasingly important, as consumers become more concerned with quality-of-life issues, particularly the adverse health effects of obesity. Unhealthy diet now ranks with smoking as a contributor to disability-adjusted life years, or DALY -- the number of years in which disabilities reduce a person's quality of life.

An imbalance between energy intake and expenditure, due mainly to excessive consumption of saturated fatty acids, and under-consumption of fruit and vegetables, are chiefly responsible for obesity -- only three per cent of the DALY figure is a consequence of eating unsafe foods.

Van Arendonk said animal breeders need to reduce the cost of producing animal protein, by developing more robust, productive, healthier and longer-lived breeds -- this would involve increased emphasis on reproductive and health traits.

"We need to analyse production systems and determine what kind of animal we desire, then translate that into breeding goals," he said. "What traits should be improved, and how much emphasis should we place on each, given that we can't win them all?"

One solution is to identify and select animals with desirable production traits, measure and record the performance of these animals and their relatives, and estimate breeding values -- how 'good' the animals are for specific traits.

The best-performing animals for these traits would then be selected as parents for the next generation, and the procedure would be iterated over several generations to make further gains.

The genomics solution

Current breeding schemes emphasise traits that can be easily measured, such as growth rate, milk production and longevity. Relatively little attention has been given to product quality, because measurement systems for quality traits are expensive, and current payment systems do not reflect quality.

"And to measure quality directly, you have to slaughter the animal, which makes it difficult to use it as a parent for the next generation," Van Arendonk said.

"Genomics is the ideal solution," he said. "All we need to do is analyse the DNA of the selection candidates and that will lead us to a complete picture of the genetic value of the animal, without the need to measure the phenotype.

"It's good to dream, but this is not realistic -- the information we get from genomics is going to be a tremendous help, but we will always need phenotype data."

Van Arendonk said cross-species comparisons of mammalian and poultry genome sequences are helping to speed identification of genes for desirable production traits in livestock.

There is 98.6 per cent homology between humans and chimpanzees, and 60 per cent homology between humans and chickens -- all vertebrates have a basic complement of around 43 per cent of genes in common.

Many of the inter-species differences involve single nucleotide polymorphisms (SNPs). On average, a SNP site occurs every 220 base pairs -- the functional significance of such differences is largely unknown.

Van Arendonk said the challenge is to identify mutations and SNPs contributing to genetic variation, using markers to track quantitative trait loci (QTLs) between generations.

For example, a sire heterozgous for a particular QTL transmits an A haplotype to 50 per cent of its offspring, and a B haplotype to the other 50 per cent. By tracking the performance of the A and B types, and ranking them for the trait of interest, geneticists could identify the chromosomal regions and genes that collectively contribute to variation in that trait.

"A number of chromosomes have been identified with QTLs contributing to milk production," Van Arendonk said. "For example, a QTL called BTAS3 has a major effect on milk fat content."

The disadvantage of the QTL approach is that knowledge of the location of their effect is imperfect; genotyping makes it possible to simultaneously estimate both the effect, and breeding values.

Constructing genotypes

Falling costs have made large-scale genotyping feasible; geneticists will now be able to reconstruct, at the genetic level, the relationships between parents and offspring.

More accurate estimates of breeding values will enable breeders to select at the embryonic stage, greatly accelerating breed improvement for combinations of commercially valuable traits.

Van Arendonk said milk protein typically comprises 78 per cent casein proteins and 22 per cent whey proteins and bioactive peptides, while fat content, and the ratio of saturated to unsaturated fatty acids, varies widely.

Holland's Milk Genomics Initiative is exploring the opportunities for modifying milk composition for specific purposes, using conventional breeding.

Researchers are analysing the protein and fat composition of milk from 2000 selected dairy cows, and applying genomics tools to identify genomes that are in the extreme range for particular constituents.

Superior cows and bulls with these traits will then be cloned to disseminate their elite genes and rapidly upgrade commercial dairy herds.