Multiplexed Shotgun Genotyping (MSG) - Genome Wide Genotyping at Low Cost and High Efficiency

Web Published:
12/1/2011
Description:

Princeton Docket # 11-2635

Researchers in Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics, Princeton University have developed a technology¿called Multiplexed Shotgun Genotyping (MSG)¿that provides genome-wide estimates of ancestry (genotypes) in a large number of individuals at low cost. MSG combines a novel approach to construct next generation sequencing libraries and includes a sophisticated statistical framework to assign ancestry and to identify recombination breakpoints. MSG is significantly more efficient than other existing technologies. In addition, MSG is extremely flexible and can be applied to a wide range of organisms. Because MSG allows sensitive detection of small genomic regions genome-wide, without prior investment in marker development, there are many potential applications in the fields of genetics, plant and animal breeding, and conservation. Two immediate market applications are in the identification of new genes in discovery research and the identification of introgressed regions in selective breeding.

 Applications in

¿ Identification of new genes in discovery research

¿ Identification of introgressed regions in selective breeding programs

¿ Optimization of captive breeding programs

¿ Tracking the effectiveness of biological control measures

 

 Advantages

¿ Low cost

¿ Does not require marker development

¿ Use of small sample size for non-invasive sampling

¿ Rapid and highly sensitive

¿ High levels of multiplexing allowing the survey of large number of individuals

Publication:

Andolfatto,P.; Davison,D.; Erezyilmaz,D.; Hu,T.T.; Mast,J.; Sunayama-Morita,T.; Stern,D.L. ¿Multiplexed Shotgun Genotyping for Rapid and Efficient Genetic Mapping¿, Genome Research, 2011, 21, 610-617.

Initial Markets

Discovery Research - Identification of new genes involved in biological processes

Scientists and companies routinely perform forward genetic screens to identify new genes involved in biological processes. This has historically proven to be the most powerful method to identify genes in biological pathways in all of the genetic model systems, including viruses, bacteria, yeast, nematodes, fruit flies, fish, and mice. In recent years, scientists and companies have moved away from these experiments, because identification of the causal mutations can be extremely time consuming and expensive. We have demonstrated that MSG can be used to rapidly map a genetic mutation to high resolution. This information on the genomic location of the mutation can be combined with whole genome resequencing, which is now available at reasonable cost for essentially all model systems, to directly identify the mutation isolated in a genetic screen. Applying MSG together with whole-genome re-sequencing would save researchers months (at least) of work and considerable expense. There is a large existing market of researchers who would be willing and able to pay for this service to accelerate their discovery research. In addition, we believe that many researchers would return to these screens if they had an easy means of identifying the mutations. A service to identify these mutations would therefore create a larger market than already exists.

Selective Breeding Programs - Identification of introgressed regions

The second market includes plant and animal breeders (including major agriculture companies)  and researchers who are developing new breeds of animals and plants through selective breeding. Selective breeding is a politically palatable alternative to the creation of genetically modified organisms (GMO), and is therefore likely to become an increasingly important source of the world¿s agricultural animal and plant breeds. Selective breeding involves the introduction of favorable traits from one strain into a second strain through an extensive series of genetic crosses, called introgression. One major hurdle to introgression experiments is to identify which individuals have inherited the targeted genome regions. A second major difficulty, which rarely is addressed directly in these projects, is to identify unwanted regions that have been accidentally introgressed, which might lead to the introduction of unwanted traits along with the desired traits. MSG provides an efficient method to solve both problems in a single experiment, because MSG identifies all introgressed regions.

Commercialization Strategy

To serve the immediate needs of the two near term market opportunities in Selective Breeding and Discovery Research we envision a start up that could initially be run with minimal personnel (as few as three people), to process approximately 2-3 samples per week. As demand increased, greater throughput could be gained by purchasing liquid handling robots and in the hiring of qualified technicians.  The entire service contemplated lends itself to automation. Many of these steps are currently performed in our laboratory with liquid handling robots. Estimated start up needs are estimated to be between $500,000 and $1.1M depending on the use of alternative computing facilities and access to HTS sequencing machines. Lower estimates of the start-up costs are based on the use of cloud computing for data storage and the outsourcing of sequencing needs. Patent protection is pending.

The Inventors

David Stern, PhD

Professor Stern is an HHMI Investigator and Professor of Ecology and Evolutionary Biology at Princeton University.  His current research is focused on the genetic causes of natural variation in appearance and behavior. His laboratory is developing new genotyping and phenotyping assays, and new genetic tools to accelerate discovery of the genes that have led to the evolution of new species.

Peter Andolfatto, PhD

Professor Andolfatto is Assistant Professor of Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics. His current research is focused on a broad range of topics in Evolutionary Genetics and combines genomics, experimental manipulations and computational population genetics approaches, primarily using Drosophila as a model system.

Contact:

Laurie Tzodikov

Princeton University Office of Technology Licensing  ¿ (609) 258-7256¿ tzodikov@princeton.edu

PU #11-2635

                                                                                                                                                                                                                                                                                               

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
David Stern
Peter Andolfatto
Keywords: