How to get past the destructive Mountain Pine Beetle using genomics

Most of the presentation was spent discussing policy implications of the impact of the Mountain Pine Beetle, containment challenges faced in limiting its expansion and the potential to mitigate economic impact on a limited budget. As is being done in livestock, genomics can be used to investigate tree resistance to disease and pests. The result in this case was discovering how drought impacts gene expression in various species of trees, reducing their ability to fend off Mountain Pine Beetle attacks.

Similarly, newly-developed genomic signatures for various populations of Mountain Pine Beetles enabled experts to determine the geographic areas from which they were invading new territories. In turn, this allowed an improved risk assessment process to feed into forestry policy due to a better understanding of range expansion and spread dynamics.

The research on gene expression showed that degree of drought has a significant impact on a tree’s resistance or ability to repel a Pine Beetle attack. Combined with the latter work on genomic signatures, this led to policy development directing resource use towards activites that defend vulnerable forest areas in times of drought and target the reduction of beetle populations from where they are most likely to invade.

From there, the discussion shifted to tree improvement, pointing out that, as is the case with breed improvement in livestock, the three main areas of investigation are end-product quality, health and efficiency. This was more accurately summarized as wood and pulp characteristics, growth and yield, drought tolerance, nutrient use or efficiency, and pest and pathogen resistance. Just like cows!

Up next was an overview of the importance of an accurate and efficient system of forestry traceability. Industry-wide, half a billion seedlings are grown each year as part of Canadian reforestation efforts. This involves massive efforts in cone collection and seed extraction (among others) as part of the transplantation back into sensitive natural environments where an unintended species can have a significant impact on the environment and equally significant financial consequences for the corporation responsible for introducing them. Genomic traceability initiatives have already played a major role as a fail-safe means of determining that the intended genetics are delivered into the intended stands

In closing, the discussion turned to the future and how in forestry, as in medicine and agriculture, the promise is in the emergence of genomics-led precision initiatives as conservation tools as well as a means to advance high-value areas of the Canadian forestry industry … or better said, as a means to better the Canadian environment, outdoor experience and economy.

From Brazil’s fierce milkers to Canada’s placid eaters

“These are Girolandos,” says Valente. “They’re a cross between Holsteins and Gyr, more adapted to hot climates and ectoparasites. The down side is that they produce less and are more… uhm… reactive during handling than the European breeds.”

Valente’s main interest is the genetic approach to behaviour in farm animals, focusing on temperament in cattle. In Brazil, one of the projects he is involved in relates to milking temperament in Girolando and associating the trait with production and health and welfare aspects. These pictures were taken at one of the farms involved in the project, the Fazenda Floresta in Sao Paolo State, which has a large herd of Gyr and Girolando. Valente’s visit had one key objective: training the heifers.

“First milking is a big problem. Sometimes they go absolutely crazy, break everything and hurt themselves,” he admits. “So we try to get the heifers used to the parlour facilities ahead of time.”

The idea is to reduce their reaction (their flight zone) and teach them about their new lives. Brave volunteers guide them into the parlour without restraints, walk around them, introduce them to new noises and new equipment. The pictures below show the “novel object test” to assess the Girolandos’ general fear of novelty.

“In this picture,” says Valente, “a group of us from Sao Paulo State University are at Girolando Bulls’ Performance Centre in Uberaba, State of Minas Gerais, measuring the bulls for temperament.”

Due to the cost of collecting semen from Girolando bulls (and, no doubt, the danger to life and limb!), a preselection test is done instead. Since 2014, bulls are measured once a month for four months for temperament, which comprises 10 percent of the selection index. The other factors are andrological parameters and body capacity measurements.

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In Canada, nothing nearly so adrenalin-pumping. As a postdoc, Valente works with Gentec CEO Graham Plastow and Gentec-associated researchers John Basarab (Alberta Agriculture and Forestry), and John Crowley (Canadian Beef Breeds Council) on feed efficiency as it relates to feeding behaviour in beef cattle.

“We know some animals spend more time at the feed bunk but are not more efficient than those animals that spend less time” he says. “So we’re looking at two traits: one for time at the bunk (duration) and the other for ‘head down’. The second one means they are eating not just hanging around.”

Valente found Graham Plastow and Gentec through another Canadian. Karen Schwartzkopf-Genswein (Agriculture and Agri-Food Canada, Lethbridge R&D Centre) is a visiting professor at Sao Paolo State University, where Valente was doing his PhD under Mateus José R. Paranhos da Costa (Faculty of Agricultural and Veterinary Sciences). There, the two developed a close professional relationship and co-authored a publication. When he was searching for an internship for his PhD, he asked her where he might study genomic tools applied to beef cattle in Canada. She recommended Gentec.

“Graham is an excellent connection,” he says. “He helped improve the quality of my PhD thesis, invited me for the postdoc, and now I have an opportunity to build a bridge between two like-minded organizations.”

Indeed, Plastow is keen to collaborate with the Empresa Brasileira de Pesquisa Agropecuária (Embrapa), the Brazilian agricultural research corporation, which has precious datasets from breed associations and phenotypes that could be useful in the Canadian context.

“Travelling between Canada and Brazil, especially to work on different projects… it’s quite gratifying,” concludes Valente.

Combining genetics and enriched environments could improve pig welfare in commercial systems.

Yolande Seddon became fascinated in the alteration of behaviour through genes and that some behaviour is “hard-wired” while studying animal behaviour and welfare as an undergraduate student in the UK. For her Master’s, she began to focus on pigs, investigating the effects of long-distance transport.

“I was amazed by how many factors there are to consider—and this is just one aspect of one industry in a much larger sector,” she says. “I decided to specialize to help make real improvements.”

Today, Seddon’s mandate is to improve pig welfare in current production systems, with a particular interest in fully-slatted systems. She admits that a number of welfare improvements could be made by moving away from slatted systems but the reality of sustainable production and affordable meat ensure their survival. She was recently awarded nearly $2 million from NSERC, USask and industry for a 5-year program to explore, among other things, how enriched environments and positive welfare can influence health and resilience to disease (see media coverage here and here).

Good pig welfare concerns how the animal is feeling and copes with its environment. So, good physical and mental health, no fear, not in want of anything, and able to respond effectively to challenges. In Canada, we want good well-being and good production to be efficient. However, if pigs fail to cope with challenges, chronic stress can develop, which can influence susceptibility to disease

“Generally, producers are aware of the link between welfare and meat quality. The challenges come when we look at behavioural needs,” says Seddon. “Animals are driven to perform some behaviours even when domesticated. When a sow is about to farrow, for example, she still wants to build a nest. However, space is at a premium, and bedding isn’t often used for hygiene reasons, so the sow’s ability to express nest building behaviour fully can be reduced.”

Seddon’s Alberta Agriculture Funding consortium funding will piggy-back (no pun intended) onto Gentec-associated researcher Michael Dyck’s current Genome Canada project.

On entering the nursery, 50% of pens will serve as controls and 50% will receive an enrichment routine that will continue as they enter the disease challenge, recover and exit the finisher. Individuals and pens will be compared for susceptibility to disease, immune response and genetic expression.

Every two days, the pigs will be exposed to new objects that have properties known to be attractive and can be destroyed, manipulated and chewed—but not eaten (pigs like to eat their enrichment). Examples include cotton ropes for chewing, rubber mats and jute sacks for rooting, Porcichew hanging enrichment, a sheet of tarpaulin for group interaction, and rubber hoses. To help the novelty (don’t forget—pigs are pretty smart!), items are removed and rotated so they won’t see them again for another two weeks.

A study in the Netherlands showed that enrichment increases resistance to disease. In this study, pigs had more space, comingling, shavings, branches and peat moss. After a challenge with PRRS virus and Actinobacillus pleuropneumoniae (APP), the pigs with enrichment cleared the PRRS virus sooner and only 7% had APP lung lesions vs 57% of pigs in the barren environment.

However, because the pigs may have been eating their enrichment, the effect on the microbiome is unknown. Seddon’s project will help break that down by identifying whether non-edible enrichment that brings novelty to the pens and offers pigs an opportunity to investigate can influence disease resistance.

So what does enrichment cost?

“The cost/benefit needs to be identified,” says Seddon. “But, a specific enrichment routine could be targeted at a specific time of production to enhance immune response. Or, if you’re building a new barn, you might invest in an overhead rail to automate enrichment rotation. You can buy purpose-built systems for that. But if production quality is important, you just make it happen.”

The premier event for researchers and professionals involved in the genetic improvement of livestock

Over 10 Gentec members attended this important conference. Gentec CEO Dr Graham Plastow chaired the fantastic session on gene editing which is a hot topic in livestock genomics in recent years. Over five days, workshops updated the genomics progress in both research and application in livestock, which significantly renewed my knowledge in genomics. The one-day field trip (sheep/deer farm) gave me a better understanding about animal breeding and production in New Zealand. The excellent conference program and social activities did wonders for my professional networking with people from academia and industry.

For me, the most attractive session was the genomics methods and tools program which spread over all five days. Powerful statistical methodology and tools have been well developed and improved in recent years, driven by the rapid increase number of phenotypes and genotypes. Single step GBLUP (SSGBLUP) is considered the most popular one in practical breeding since it can handle large pedigree, genotypes and various types of phenotypes simultaneously. SSGBLUP + APY (algorithm-proven young for easier G inversion) is widely used in the US to evaluate beef cattle and by pig-breeding companies (e.g. Topigs Norsvin and Genesus Inc.). However, SSGBLUP still needs to improve minor issues, such as the weighting of SNPs.

Another valuable session was on how to improve genomic prediction accuracy especially with whole genome sequence data, which has been a main research topic in Gentec under several projects in cattle and pigs in collaboration with our industry partners. According to a discussion with Drs Mike Goddard and Ben Hayes, they both thought that, theoretically, by adding the TOP SNPs selected from whole sequence, the accuracy of GEBV should be better or at least remain the same.

As many reports in the conference demonstrated, results from practice data are not always consistent. We faced a similar situation as described in the paper we published recently (Genomic evaluation of feed efficiency component traits in Duroc pigs using 80K, 650K and whole-genome sequence variants). We all agreed that possible solutions include increasing the number of training animals especially including the target breed, increasing the number of SNPs especially the causal ones, using Bayesian methods (e.g. BayesRC) and multi-omic data (gene expression and annotations).

Another interesting area was genomic studies in pigs. Several presentations talked about GWAS and/or genomic prediction for economically important traits in pigs we have studied widely at Gentec. Their results were quite comparable with ours. For example, important QTL were reported for the number of stillborn (SSC9) and the number of born alive (SSC2, 5, 9, 14). Many putative lethal haplotypes associated with sow fertility were detected, and the region on SSC14 was also detected in our Duroc pigs. There were also a few talks in hot-topic areas such as novel predictors or selection criteria for pig growth, pork quality and reproduction, such as hemoglobin levels and gut microbiome. We have investigated these topics in recent projects to improve resilience to disease through genomics.

Richard (known as Glen) Uhrig, currently Assistant Professor at UAlberta’s Department of Biological Sciences, became interested in the circadian clock and light signalling of plants during his post-doctoral fellowship in Switzerland. There, he worked with world renowned plant scientist Dr. Wilhelm Gruissem at the Swiss Federal Institute of Technology on a multi-national EU Seventh Framework-funded project call TiMet Metabolism, which sought to better understand how the circadian clock is connected to plant metab

Glen’s own EU Marie-Curie Plant Fellows Co-Fund and NSERC post-doctoral fellowship-funded work spun out of this, and aimed to understand how and when proteins and cellular processes are regulated post-translationally over a 24-hour diurnal cycle. He explains it this way. “Humans have a circadian clock to govern physiological processes. Similarly, plants have a circadian clock but, to them, it’s a matter of survival.”

Through this work, he acquired a number of large datasets that are the foundation of his research program at UAlberta as well as a number of exciting leads.

“It’s very fundamental work” he says. “But we are looking at new avenues that could be relevant to agriculture.”

The circadian clock controls numerous cell processes including aspects of plant metabolism. When you understand how these processes are regulated at a high level, you can start to engineer or breed plants for specific traits. The possibilities are mind-boggling.

Among the findings are a number of cellular processes that are fluctuating dynamically at the protein level over the course of a 24-hour photoperiod. One of these processes is how well plants take up nitrogen and how much nitrogen they need to grow well. In most crops, nitrogen is provided in the form of high-energy fertilizers but the plants need carbon (from sunlight) to assimilate it. Glen’s lab found that a number of the core and related proteins for assimilating nitrogen are regulated by multiple post-translational modifications. These then correlate with the presence or absence of available carbon for assimilating nitrogen.

In the meantime, Glen is relishing the idea of starting a research program, and exploring unique niches—of which beef genomics is one. Shortly after arriving at UAlberta (he’s only been here six months), he reached out to Gentec CEO Graham Plastow and attended Gentec’s annual conference in October. Discussions may lead to another cloak-and-dagger collaboration that would integrate Glen’s expertise in proteomics and genomics into a large scale project called 5-dimensional omics that aims to create a comprehensive understanding of Alberta agriculture at the molecular level; from ground to grocer genomics.

“I’m taking advantage of opportunities to meet people such as Graham and beef producers,” he says. “The conference was eye-opening. Here’s a group of people specifically interested in engaging with academics and in using cutting-edge science. Probably, most people think these two groups don’t talk—but a lot of interesting ideas come to light when those connections are made.”

Having worked on various genomics projects that included human, bovine and the SARS coronavirus, Steven Jones, Co-Director and Head of Bioinformatics of the Genome Sciences Centre at the BC Cancer Agency in Vancouver, is well versed in the potential, development and application of genomics. As he said in his presentation, “Cancer is a genetic disease. [And] livestock too is all about the genetics.”

In many ways, human cancer genomics and treatment can be considered the “pointy end of the stick” given the cost and complexity of pursuing these solutions. In spite of this, parallels are plentiful, and the tools developed in the human sphere often trickle down to our pets and livestock. For example, understanding how and why certain genomic variations differentiate between an aggressive and benign tumour allows us to manage the tumour appropriately. This ability provides value in the same manner as understanding the variants that result in Angus instead of Hereford cattle.

These days, the computational analysis (not the sequencing effort) consumes most of the resources in the process of teasing out the genomic variations, insertions, deletions, copy number variations, regions where zero heterozygosity remains (indicating the loss of a chromosome) and expression necessary to develop genetically specific treatment protocols.

In doing this, the processes flow from discovering knowledge, learning how best to understand and interpret it, and transferring it to the end user, be they clinician or producer. Communication is always the critical element: “Some buy into it [the technology], and some have yet to be convinced. It’s a huge endeavour.”

Either way, for Jones, it’s a team pursuit involving 24 individuals across multiple disciplines who sequence [about] one human genome a day, progressing the science and ultimately looking for a cure.