Laboratory animals are the source of major discoveries and breakthroughs in biology, not just in tackling disease but also unravelling fundamental molecular processes.
Delegates at a recent research conference organized by the European Science Foundation (ESF) and Wellcome Trust heard how technology capable of analyzing animal genes across the whole genome is yielding many benefits for agriculture and human society.
In breeding both domestic and farm animals for example, it is now possible to select individuals with a wide spectrum of desirable traits in a single generation. In the past selective breeding of animals has been confined to traits that are obvious or easy to measure, and it has been difficult to produce individuals with a broad combination of desirable qualities, according to Helen Sang, chair of the recent conference.
“There is the potential to increase the effectiveness of genetic selection, even for traits that are difficult or take a long time to measure,” said Sang from the Roslin Institute Department of Gene Function & Development Edinburgh United Kingdom. The key point here is that it is now possible to identify individual animals for breeding, and select offspring, with the best overall combination of gene variants (alleles) rather than focusing on just one or two traits. Sang is also
This ability to measure whole genomes is also helping unravel the genetic components of many multi-gene diseases in both humans and animals. “It is impressive how quickly specific mutations can be mapped in farm animal species and the dog, now that genome sequences are available and SNP maps,” said Sang. SNP, or Single Nucleotide Polymorphism, refers to the single point variations between the DNA of individuals of a species that determine traits. These lead to the existence of different versions of some genes, called alleles, and in some cases these variants arise in an individual through mutations in a single nucleotide. It is now possible to pinpoint mutations across the whole genome quickly and study how the associated genes interact. “This information can be used to investigate disease in these species but also in many cases can be useful models for similar human genetic diseases,” said Sang.
The conference showed how fundamental breakthroughs can be exploited in tackling disease. One of the most exciting discoveries of recent years is the fact that rods and cones are not the only light receptors in the eye, overturning the long established view. There is also a receptor, called phototropin, that recognises blue light at much lower levels, even operating in some people who are otherwise blind, playing an important role in setting the circadian clock. At the conference, one of the world’s leading specialists in chronobiology (study of biological rhythms) Russell Foster, explained how mouse models were being used to study this newly discovered blue light receptor. “This has been analysed in mice and he is using the knowledge gained to interact with ophthalmologists (eye disease specialists) and patients,” said Sang.
Genes determine individual traits not just through their variations, or alleles, but also through differing levels of expression. Another important field of research discussed at the conference concerned the important role of microRNAs in controlling gene expression. RNAs are normally the intermediate molecules between DNA and their products, proteins, in gene expression. However microRNA is a type of RNA that instead of being involved in protein production, feeds back into the DNA coding process to regulate the expression of other genes. Mutations in the genes coding for the microRNA itself can therefore effect the expression of other genes, with some subtle and occasionally dramatic effects, as Sang pointed out. Given that animals inherit two copies, or alleles, of each gene, mutations are more likely to be effective when one of the copies is already silenced, as happens in the phenomenon known as genomic imprinting. Sang cited the case of sheep, where imprinting of a gene called callipyge leads to increased muscle growth in the hindquarters, which clearly can be a desirable trait in meat production.
All these different strands of research could benefit from being integrated into a common framework to avoid duplication of effort and exploit relevant expertise, according to Sang. “The main value of the workshop was that it brought the more theoretical people together with experimental scientists and opportunities for synergies were identified.”