Researchers aim to pinpoint non-gene components in DNA linked to production and welfare traits in cattle, gaining insights across species.
Researchers are developing a method of identifying specific letters in the DNA code that govern the development of key physical traits, such as productivity or disease tolerance, in livestock. The study, involving Roslin researchers and their commercial partner Annogen, will focus on identifying sites in cattle DNA linked to important genes for livestock production and welfare.
The Roslin researchers will use a high-resolution approach to precisely identify sections within the DNA code that behave like switches to directly control gene activity. These switches, known as regulatory elements, govern whether individuals will exhibit the characteristics associated with a particular gene.Their approach will use a technology provided by Annogen that improves on low-resolution techniques that spot only the broad regions of DNA in which these regulatory variants reside.
This technology, known as Survey of Regulatory Elements (SuRE), helps to identify those variants and mutations that can be linked to key physical traits, such as productivity or disease tolerance, in livestock. Insights from the study could aid the use of gene-editing technology targeting these regulatory variants to give rise to the preferred traits in livestock.
This approach builds on previous studies showing that most variants and mutations that give rise to differences between individuals in a species are found in regulatory regions of DNA. Roslin scientists will also aim to develop statistical models for predicting where such DNA regions might be commonly found in the genetic codes of many species, which could give valuable insights into health in humans and provide a roadmap for studies in other species.
Their project is funded by a Biotechnology and Biological Sciences Research Council award of almost £750,000.
Genome-wide trawl
Researchers will apply lab and computer-based methods to simultaneously test the impact of millions of genetic changes on gene activity in the two main cattle sub-species. This will help generate a map of key DNA changes linked to gene activity. By intersecting these variants with regions known to control important cattle characteristics, researchers hope to identify the specific DNA changes underlying important welfare and production traits. Their outcomes will help predict which genetic changes in cattle would impact on traits to inform selective breeding.
“We know the regions of DNA responsible for many production and disease characteristics in livestock, but not the precise genes and DNA changes involved. This is a major barrier to improving production traits through breeding and genome editing. If we can map which DNA regions directly impact gene activity, we can determine which genetic changes are most likely driving the observed changes in key traits. We hope this will substantially improve the rate at which we can improve important characteristics in livestock.”, Dr James PrendergastCentre for Tropical Livestock Genetics and Health at the Roslin Institute
“In this project our SuRE technology will help identify genomic regions that control gene activity while at the same time screening millions of genetic changes to identify the most likely high-impact ones. Normally our clients are pharma and plant breeding companies, so we are very excited to be working with the experts at Roslin to apply our technology in livestock research for the first time.”, Dr Joris van Arensbergen,CEO, Annogen
** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **
About Annogen
At Annogen, we use our SuRE™ technology to identify regulatory DNA elements to be used for controlled (therapeutic) gene expression. Also, we establish databases in which we functionally annotate millions of non-coding sequence variants for their effect on promoter and enhancer activity. This enables researchers to qualitatively interpret non-coding sequence variants in humans, animals and plants in the way we already can for coding sequence variants. For more information, please see our proof-of-concept study published in Nature Genetics https://rdcu.be/bH2xl where we annotate 6 million variants in 2 cell types.
Further information
Victor Schut, CBO at Annogen, [email protected], phone: +31 614597016
