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Table 2 The role of functional genome annotation in addressing key challenges for salmonid research and its application. Below we list selected key questions, highlight their importance, and then briefly describe (in italics) how the FAASG initiative will help address them

From: Functional Annotation of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture

Aquaculture

 What is the functional genetic basis of key performance traits for salmonid aquaculture?

  Few causative variants underlying performance trait QTL have been identified. Knowledge of the precise functional variants underpinning QTL will inform the biology of these traits, and facilitate cost-effective selection for favorable alleles.

   Genome annotation is essential to prioritize candidate causal variants. Many traits are influenced by non-coding variants influencing gene expression. The FAASG initiative will aid identification and prioritization of QTL-region variants for key traits.

 How can we optimize genomic selection for genetic improvement in aquaculture breeding programs?

  Genomic selection can accelerate genetic gain for traits important to sustainable and profitable aquaculture, such as host resistance to infectious diseases. Predicting breeding values in distant relatives to the training population is challenging, thus necessitating frequent, expensive phenotypic tests.

   The likelihood of SNPs having a functional effect on a trait can be estimated using FAASG functional annotation data. These SNPs can be prioritized in genotyping panels to enable improved prediction accuracy, and persistency of that accuracy, across diverse genetic backgrounds and multiple generations.

 What is the functional genetic basis of recent domestication in salmonid species?

  Salmonids are excellent models to study the genomic basis of recent domestication, facilitating discovery of genetic variation of importance in adaptation to aquaculture environments. These outcomes can improve hatchery management, health and welfare of farmed fish, and have implications for interactions with wild populations.

   Domestication is likely to have a polygenic basis and be largely due to modification of gene regulation including control by epigenetic mechanisms. Functional annotation is essential for researchers to identify sequence and epigenomic variation linked to domestication and the response to artificial selection.

 How can genome editing technology contribute to improved aquaculture production?

  Genome editing technology, notably CRISPR-Cas9 has potential to enhance aquaculture production directly by introducing favorable alleles into farmed populations, or indirectly, for example by providing a better understanding of the functional basis of production traits (e.g. using gene knockout). While regulatory and public acceptance is required, the potential is highlighted by several high profile successes in terrestrial livestock.

   Choosing the correct target to edit is essential, and requires accurate annotation of the reference genome. A function of a SNP, epigenetic mark, non-coding RNA, coding RNA or whole protein can be determined using gene editing. The technology can also be applied to demonstrate causality of variants underlying QTL.

 What is the long term impact of aquaculture escapees on wild populations?

  Evaluating and understanding the impacts of aquaculture escapees on wild populations supports risk assessment for the use of native and non-native strains in culture.

   FAASG will improve understanding of the functional differences among populations resulting from genomic variation, and will guide development of tools to effectively track and monitor the genetic impact of escapees on wild populations.

 How can measurement of salmonid health and welfare in aquaculture be improved?

  Appropriate biomarkers of stress, health and growth status in salmonid aquaculture are currently difficult to define and far from comprehensive.

   An improved understanding of the genetic and epigenetic regulation of key physiological systems supporting fish health will be guided by the annotated genomes, networks and comparative biology, and will facilitate development of tools to help monitor animal wellbeing in culture.

Ecology, evolution and physiology

 What role did the whole genome duplication and subsequent rediploidization play in salmonid evolution?

  This is a long-standing question of fundamental importance to our understanding of salmonid biology and the role of WGDs in evolution more generally.

   Comparative genomic annotation will improve understanding of how sequence and functional variation arising post-WGD are coupled to trait evolution, including the lineage-specific evolution of anadromous life-history, which has been linked to species radiation.

 How important is genetic vs. epigenetic variation in regulating trait variability?

  Rapid phenotypic divergence and phenotypic plasticity are hallmarks of many salmonid species, yet remain poorly-characterized. An improved understanding of heritable epigenetic variation and its interaction with both genetic and environmental variation can be exploited in both conservation and aquaculture.

   Functional annotation of epigenetic marks in salmonid genomes, and studies into the role of epigenetic regulation in determining trait variation and phenotypic plasticity are key goals of the FAASG initiative.

 What is the genomic basis of response and adaptation to natural and anthropogenic stressors?

  Human-induced environmental changes, including climate change, are already negatively affecting salmonid populations. Understanding the role of genetic and epigenetic variation in physiological response to these changes will be key to predicting, and potentially mitigating, these effects.

   Improved understanding of the functional genomic basis of differential responses to environmental stressors in salmonids may be applied to inform forecasting, mitigation and remedial strategies for challenges associated with anthropogenic-induced changes in ecosystems, including through climate change.

 What role do ‘non-coding’ RNAs have in generating phenotypic variation?

  The functions of non-coding RNAs are poorly understood in salmonids. The greater retention of miRNAs in comparison to duplicated genes after WGD suggests important functions in coping with a duplicated genome. Non-coding RNAs may regulate traits of interest to aquaculture and evolutionary biology.

   Comparative functional annotation in salmonids will highlight the location and role of non-coding RNAs in regulation of gene expression and downstream regulation of complex traits.

 How many salmonid species exist, and how can we distinguish them?

  The actual number of salmonid species is unknown. Habitat-dependent phenotypes can suggest different species, but genomics and functional genomics methods are ultimately required to answer this question.

   Diverse salmonid species and populations will be targeted in FAASG, providing comparative genome sequences and annotations. This will facilitate development and application of species-specific markers to assess the quantity and diversity of species in the salmonid family.