The scientific development that we need in the animal breeding industry

Abstract

Our new JABG executive editor asked me to write an editorial on current and future needs for research in our area, from an industry point of view. This made me remember that I was involved into something similar 10 years ago. So, it is time for an update, and for some reflection—always interesting. FABRE-TP is a European Technology Platform dedicated to Farm Animal Breeding & REproduction. Such ETPs are industry-led forums that develop R&D agendas. Those agendas are used at the EU and national levels to get support for funding (see tinyurl.com/u4wvxk9); that is, a think tank—just what we need for needs for research in our area. In 2011, FABRE-TP published its Strategic Research Agenda (SRA) (see tinyurl.com/wkqynrt), a 48-page document that was put together out of input from 55 members of 13 expert panels, each panel focusing on themes such as food quality or robustness, on animal species from honeybees to horses or on technologies such as genetics or genomics. For JABG readers, the most relevant part is in those technology chapters and the overlapping bits of the theme and species chapters. Time frames of five, 15 and 25 years were set for research needs, and that was 10 years ago—so let's see how far we have come with the 5-year one and what progress has been made towards the 15-year one; and if there is anything new, by now. I have omitted anything that is about policy rather than research—and filtered according to my own interests and prejudices. In another dimension, the entries for research needs cover traits, methodology and issues. Traits. Perhaps surprisingly, only one conglomerate of traits really features in the SRA: robustness and resilience, with a few extensions to animal behaviour and welfare traits. Practically every chapter lists it as a short-term priority and often also as a medium-term one. So, the species-oriented people seem to be more or less happy with their current ability to influence the regular production and reproduction traits, and that is a very good thing in itself. A few decades ago, we used to refer to these robustness traits as “secondary traits”—and by now, they have evolved to hot item #1 in livestock breeding: very clearly a main (and wide open!) field for research to focus on; and since then, we have seen an increasing interest in behavioural traits too. Methodology. Of course, the “current ability to influence the regular traits” of above has much to do with the worldwide move to genomic prediction that was just past its implementation infancy in 2010 (we were all busy blending polygenic and genomic EBVs at that time: Single Step was still to come). So, again not surprisingly, the second hot item in the SRA centres around genomic technology, with entries ranging from “optimal implementation of genomic data into genetic evaluations” (from the Cattle panel, with much focus on across-breed evaluation and data systems that were then too large for Single Step) to “fully annotated quality genome sequences with massive discovery of variants” which is still on everybody's wish list, and increasingly so. We all know that GBLUP needs proper training of its markers more than anything else, so the other SRA's hot methodology is of course phenotyping. This is very much a matter of kitting out the proper equipment to measure things: that is not for JABG. But once the Big Data on milk, body weight, feed intake, activity, body temperature and whatever else is being streamed into our databases, we will need some very robust methodology to (a) handle and manage it and (b) convert it to meaningful information for genetic evaluation, for example by relating the volatility of within-animal records over time to the resilience traits that form the hot issue of the near future—as we saw above. The also-hot animal behaviour traits of above would benefit from the same. And then there is the concept of what we used to call “biomarkers” a few decades ago, now known as metabolomics. There are chips available now that produce readings of a few hundred metabolite concentrations in the drop of blood applied to them. Here, we really need a good evaluation of the equivalent of the candidate gene approach versus anonymous DNA markers: Do we maximize the relevant information out of all these data by understanding what each metabolite actually does in the body, or is the black box a more hopeful approach? Both these methods have to do with the accuracy of breeding value estimation. The next important part of the breeder's equation is the generation interval: always more a matter of proper logistics than of science. But the SRA mentions “schemes incorporating large-scale genotyping at the embryo level” as a medium-term priority, bringing us back to the concepts of velo- and whizzogenetics of the 1990s: apply GBLUP to extremely young animals, select them, and propagate them artificially. Later, the concept of Iterated Embryo Selection came up, which would involve stem cells for the same purpose. Question 1 would then be why those schemes never made it to implementation in livestock breeding practice, leading to question 2: And what could we do about that? For the JABG community specifically, how should such large-scale genotyping schemes be organized, so as to maximize the efficiency of the breeding programmes they feature in? The Genetics panel of the SRA has an entry “metagenomic sequencing of microbial communities, e.g., in the gastrointestinal tract,” but none of the other panels seem to have been aware of the microbiome and how it influences practically everything, as was widely discovered a few years later. I would suggest that for the JABG community, the main focal issue should now be to evaluate the microbiome's composition as a novel breeding goal trait versus a novel element of the mixed model equations in MGBLUP, and in the latter case, to design the next-generation Single Step approach. Another noticeably absent methodology in this 2010 text is genome editing, of course. But let's leave that to other journals, for now. Issues. As long as animal breeding has been seriously practiced, we have been worrying (usually very silently) about the selection-induced erosion of the genetic variation that we all make a living off: the third element of the breeder's equation. The SRA has the same worries, particularly in relation to the genomic prediction methodology of above that it is so enthusiastic about at the same time. The livestock breeding literature holds a large handful of studies that show no erosion, and a very few others that show the opposite. But the worry remains, so this is a fertile ground for research, particularly in this era of whole-genome sequencing. For example, can we quantify Eitan & Soller's selection-induced genetic variation by now and get it under control? More proactively, is there a safe way to increase recombination rates and introduce some negative erosion? The same holds for genetic antagonisms; this is one of my personal hobby horses and the SRA is repeatedly worried about them too. Unfavourable genetic correlations between traits make it hard to deliver the breeding goal, and this may well be one of the most important limitations to all genetic improvement in livestock. The point is to align G (the genetic covariance matrix: what the population is capable of) with b (the index weighting factors: what we want the population to do). Walsh & Lynch (2018) posed the terrifying question: Is there genetic variation in the direction of selection? Some populations will have a G eigenstructure that fits b more easily than other populations do. This should be a crucial element in the design of the breeding goal for a population or, more interestingly, the other way around—especially for crossbreeding systems where several lines with their variable strengths and weaknesses can compensate each other. It assumes availability of many lines, as in poultry breeding and increasingly so in pig breeding. There is lots of fundamental research to do here. And the final part: the SRA mentions the need for animal geneticists to collaborate much more intensively with animal nutritionists. Even genetically improved livestock does not generate animal protein out of thin air. Nutrition must remain in sync with ΔG; otherwise, genetic improvement is commercially futile because the added value will not be expressed. Multidisciplinary research is always highly praised, but it is very rarely practised. We need some significant groundbreaking here. Just the same towards epidemiology, of course. Enough about the FABRE-TP SRA. In his Thank you! editorial of late 2019, Asko Mäki-Tanila, our former executive editor, wrote: animal breeding research has advanced in steps of some 10-20 years apart: BLUP, REML, MOET and genomic EBV. It is now almost 20 years from the latter [i.e., Meuwissen et al., 2001] and time for another groundbreaking article. Hein van der Steen and I argued something similar during an FAO meeting in Rome in 2009 (tinyurl.com/wblaoxs, page 6). And we seem to be crossing a new watershed: as Hein and I forecasted quite accidentally, now in 2020 the livestock breeding sector is in for a decade (or two) of what John Woolliams once dubbed quantomics and what comes back to the “fully annotated quality genome sequences with massive discovery of variants” of above. So, the upcoming challenge for the JABG community will be to make those discovered variants (particularly the causal ones) work more effectively than today's black box does; apply that to longitudinal Big Data phenotypes, focusing on robustness and resilience and behaviour traits, and your research should be in business. And then go and write that groundbreaking article for Asko.

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