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Genetic Mutations: Menacing or Misunderstood?

Mutations might sound like something from a zombie movie, but they aren’t always evil. For proof, look no further than the Genome Alberta project to develop and apply more accurate genomically-enhanced breeding values for traits of importance to the Canadian dairy industry. In pursuit of their goals, researchers know that working with mutations, also known as structural variations, is critical to success.

Structural variations (SVs) are chromosomal rearrangements such as deletions, insertions and inversions that may affect the activity of particular genes or entire metabolic pathways. When looking for structural variants associated with a trait, researchers are trying to reveal a correlation between phenotype - traits of interest to industry such as carcass quality, feed efficiency and methane emissions - and genotype.

The merit of mutations

“Identifying mutations that affect phenotype gives us a better understanding of the underlying biology for traits of interest,” said Dr. Kirill Krivushin, a postdoctoral fellow in the Stothard Research Group. “With this knowledge, we can more accurately predict the possible effects of genetic variations on other traits and determine other methods of trait modification, such as diet changes. Discovering mutations can also enable more accurate and robust predictions, especially across populations.”

When causal mutations affecting feed efficiency or methane emission are discovered, they will be used in the calculation of genomic estimated breeding values (GEBVs) for these traits. This will involve adding them to genotyping panels that are currently being used by industry, which are regularly updated to accommodate new markers.

Doubling the database

Of course, in order to accurately predict GEBVs, the reference population used must be very large, so researchers are working to attain that.

“We have doubled the number of Holstein sequenced bulls through the sequencing of 50 additional Holstein bulls. Also, for validation purposes and comparative studies, we have analyzed over 500 genomes of major cattle breeds. The new sequence data will be submitted to the ongoing 1000 Bull Genomes Project [a project that is combining sequence data on 1000 bull genomes], which will in return provide us with genotypes from hundreds of additional Holsteins for use in imputation. For structural variant discovery we will use the newly sequenced animals and the 48 existing Holstein genome sequences from the Canadian Cattle Genome Project (CCGP) [an international project that includes researchers from Alberta, Ontario, Australia, USA, Ireland, Scotland and New Zealand].”

Labor pains

Working with structural variants and gathering the proper data is complex, time-consuming work, but there’s little doubt the end result will be worth the effort.

“Retrieval of phenotypes is a very difficult and expensive procedure required for genetic improvement of feed efficiency and methane emissions. While there has been no direct selection for these traits on a major scale thus far for dairy cattle breeding, we have the chance to address this using the latest genomic approaches.  To do so, however, we must have accurate phenotypes for genetically-representative animals from the Canadian population.”

With that in mind, researchers on this project are using genomics to gather relevant data that allows them to calculate genetic merit for a specific animal.  Industry can then use this data and incorporate the traits of feed efficiency and methane emission to develop the strongest possible herds, even for young animals without phenotypes.

Given that there is strength in numbers, Genome Alberta is collaborating with international research partners and industry networks to confirm that new data is standardized and can be used to benefit Canada’s dairy industry while enhancing global food security and sustainability.

“Structural genomic variation will be used to select bulls whose daughters convert feed to milk more efficiently and emit fewer greenhouse gases without decreasing production. As any producer knows, feed is their largest expense, so anything that boosts feed efficiency will also boost their bottom line.”

Making this a true win-win is the fact that more efficient animals  produce less manure waste, lowering the industry’s environmental footprint and ensuring that what’s good for producers is good for the planet.

That’s not to say there aren’t harmful mutations. But given the benefits of these structural variants for the dairy industry, the only scary part is the years of education needed to fully understand them.


Genetic Mutations: Menacing or Misunderstood?

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