Population Genetics Technologies: Genomics for all
The development of high-throughput technologies has led to a surge in genome-wide studies of common, complex diseases. However, the impact of a particular genomic region may be difficult to detect - either because the effect of that region is, in itself, modest or because, across the population as a whole, many different regions contribute to disease. Such studies therefore need to analyse large samples, making them technically and financially possible only at high-throughput specialist genotyping facilities.
Although recent studies have been enormously successful in implicating genomic regions in specific diseases, they are expensive and pick up only the most common risk-increasing alleles. It is likely that many common conditions will be influenced by a large number of alleles of smaller effect that, although rare, collectively in a population have a significant impact.
To pick up these rare alleles, very large numbers of well-characterised individuals would need to be studied - a major undertaking. Anything that made this kind of study easier to carry out could therefore make a big difference.
Population Genetics Technologies is a new company set up to commercialise a technological solution to this problem. It is developing a system that will drastically reduce the amount of work involved in sequencing large numbers of samples - its aim in initial product offerings is to increase productivity by at least an order of magnitude.
The technology, initially developed by Nobel Laureate Sydney Brenner and Sam Eletr, founder of Applied Biosystems, is based on a number of key innovations:
- DNA from a population is pooled for sequence analysis, so genotyping does not have to be carried out individually for each member of the population
- the amount of sequencing is reduced, by restricting analysis to genomic regions that differ from the reference genome population
- a biochemical tagging system is used to label the DNA from each individual, so the origins of each DNA fragment in the pool can be traced back to a specific person.
The net effect is that the costs and work of genotyping a population are significantly reduced. Moreover, as the new technology complements rather than replaces existing sequencing machines, it would still be applicable as new sequencing technologies or machines are launched.
In addition, as high-throughput studies become more affordable, the number of labs able to use the technique should increase.
Population Genetics Technologies received £1.1 million start-up Wellcome Trust Technology Transfer funding in 2005. Having successfully demonstrated the feasibility of its key technologies, in February 2008 the company raised £3.7m in venture capital funding to test the combination of these technologies in integrated workflows and to validate their use with small population samples. Assuming this stage goes according to plan, scale-up to larger populations should be straightforward.
The Population Genetics Technologies approach stands to make a big impact on genetic studies, facilitating hunts for the rare variants that conventional analyses have struggled to detect.
Equally significantly, by ‘democratising’ the ability to analyse entire genomes at reasonable cost, it opens up the prospect of additional studies of specific subpopulations, such as those with a subtype of a condition, in a particular geographic region, or from a particular ethnic group.
The market also extends to other fields that are searching for the genetic basis of biological traits, such as the plant-breeding community.