Thursday, June 1, 2017

BIF 2017: Where are we going with genomics and genetic improvement

Matt Spangler
University of Nebraska-Lincoln

Alison Van Eenennaam
University of California-Davis
 
Early DNA tests with 1 or 2 markers had little predictive ability.
As tests improved, more markers were added.
Eventually there was a switch to genomic predictions. 
Unfortunately, early on, these DNA test results were published along side adjusted phenotypes, ratios, and EPDs. 
Quantitative genetic methods solved this problem by combining the molecular breeding value (MBV) with the EPD. Two approaches were used to combine MBVs with EPDs. One approach is to fit the MBV as an indicator or correlated trait. This is similar to combining carcass records with ultrasound records. The other approach is to blend the two predicts, MBVs and EPDs, as an index. 

There are two fundamental camps for implementing single-step.
  • UGA- ssGBLUP Misztal
  • Theta Solutions/ISU - BOLT Garrick, Golden, Fernando

Before, we were trying to fit genomic prediction into established genetic prediction systems. The move to single-step is the first real redesign of genetic prediction systems. These new systems will have genomic prediction at their core.

We now have the ability to do gene editing. These methods use a molecular scissors, such as meganuclease, Zinc finger, TALENs or CRISPR/Cas9, to cut both strands of DNA. When the cell repairs this double-strand break, a new deletion or insertion can be created. Or, a new piece of DNA, a donor sequence, can be introduced into the chromosome. This can allow us to move DNA from one breed into a different breed of cattle. 

"I see genome editing as the cherry on top of the breeding sundae," Van Eenennaam said. Genome editing is not a silver bullet. It will add to, but not replace, other breeding methods. To do genome editing, we have to know the DNA variant responsible for the phenotype.

An example. We could cross Belgian Blues and Nelore to get double-muscled Nelore. Or, we can edit the Nelore myostatin gene to make it match the Belgian Blue version, and create a double-muscled Nelore. Another example is creating a polled Holstein using the Angus sequence resulting in polled cattle.

Right now, the FDA has draft guidance saying that they are going to be regulating every genome edit as a new drug. This regulatory environment will limit the use of this technology in livestock production.

A lot of people believe that high accuracy sires have more consistent progeny. This is not true. 
Mendelian sampling leads to variability in a calf crop. By chance, a calf could inherit all of a bull's favorable variants, or a calf could inherit all of a bull's unfavorable variants.

Genomic predictions have not worked across breeds. [However, watch for research from my group on this subject.]

Genomic technology is great. "The entity that fully leverages trait information will win the race. Phenotype is still king," Spangler said.
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