The Bovine Pangenome Consortium
June 1, 2022
Written By: Dr. Larry Kuehn
Cattle producers use genetic predictions to select animals as parents for traits of economic importance such as calving ease or yearling weight. Historically, genetic predictions were based on the performance of relatives, which was a successful but relatively slow and labor-intensive method. The emergence of approaches that use DNA sequence information to predict performance provided the means to derive these predictions earlier in the life of the animal and with more accuracy. Each cell in the body contains over 3 billion DNA ‘bases’ or genetic pieces of information collectively called the genome, and the precise sequence of bases in the genome varies between individuals and creates the genetic differences we observe in an organism. Reading and interpreting all these bases is known as genome sequencing.
Genome sequencing (determining all the genes and pieces of genetic information in an individual) and subsequent genome assemblies (putting it all together in a genetic map), first published for cattle in 2009, have revolutionized our understanding of the genomic effects that are responsible for variation in economically important traits in cattle. The public genome assembly for cattle allowed all major U.S. cattle breed associations to add DNA sequence-based accuracy to genetic predictions used to select superior breeding cattle. These advancements have been widely implemented in the cattle industry and are certainly providing great benefit to cattlemen, but they may not serve all cattle lines and breeds equally since the original genome assembly was based on a single Hereford cow. Variation in the genome, including additions or deletions of larges stretches of DNA that may be unique to one breed of cattle, cannot be observed using standard methods and the standard genomic assembly of the single Hereford cow. However, it is precisely these differences that may be responsible for substantial and diverse genetic differences that we observe within and among breeds.
The solution for enhancing the application of breed-specific genome variation to genetic prediction is to generate additional genome assemblies of other breeds beyond the Hereford reference assembly. This approach has the potential to better characterize genetic diversity and fill in the gaps of genetic knowledge for the beef industry. Combining these assemblies in a large reference pool, termed a ‘pangenome’ will allow researchers to characterize all the genomic differences in cattle as a whole including species from all bovines around the world. To accomplish this goal, the USDA, Agricultural Research Service (ARS), including the U.S. Meat Animal Research Center (Clay Center, NE), along with 42 institutions around the world have developed the Bovine Pangenome Consortium to sequence and gather as many diverse cattle genome assemblies as possible from cattle all over the world.
Recent advancements in genomic sequencing technology and improved methods to form genome assemblies, have made the creation of the pangenome resource possible. A new assembly method that produces high-quality reference genome assemblies using a process known as trio-binning has been critical to this project. Briefly, with trio-binning, a male and female from two diverse cattle breeds, or even from other bovid species (e.g., Bison, Yak, etc.), are mated together to produce offspring with a very diverse, crossbred genome. Both parents and the progeny are then sequenced to build a long, continuous genomic sequence for each cattle chromosome. This technique has resulted in genome assemblies for beef cattle that are 250 times more continuous (accurate and complete) that the previous single-animal assembly.
As of now, prototype projects have been completed resulting in new, highly accurate assemblies of eight U.S. breeds. With all these cooperators from many different locations, all with their own unique cattle resources, the group will be able to target cattle lines that are highly diverse genetically which will provide a much more complete pangenome for the beef industry. The consortium will identify characteristic genomic alleles among all the breeds which will increase the value and impact of genomically-enhanced genetic predictions for producers in all cattle breeds. This extraordinary project promises to provide extraordinary value for beef industry producers and ultimately consumers around the world.