Accelerating Genetic Gain in Animal Production

Accelerating Genetic Gain

Flow of Information

• Artificial selection in farm animals manipulates the 'flow of information' to enhance animal products to better satisfy human demand.
• This practice has a 10,000-year history, beginning with domestication.
• Artificial selection matured as a discipline in the mid-1700s (Bakewell and Coke).
• Detailed pedigrees were used to inform breeding decisions (NRM).
• Intensive farming practices were implemented for broilers, pigs, and dairy cattle in the early 1900s.
• Genome assemblies occurred between 2000 and 2010.
• Molecular data (primarily SNP) is used to characterize genetics (GRM) using post-genomic tools.
• Molecular EBV (Estimated Breeding Value) is utilized.
• GMOs (Genetically Modified Organisms) emerged in the 1980s for plants, recently for some animals, and hold future potential.

Understanding the Past

• The map illustrates the origins of various crops and domestic animals across different regions like North America, Mesoamerica, Southern Europe, Africa, and Asia.
• The domestication practices either arose independently or spread through diffusion.
• Some species, like pigs, seem to have independent development in different areas.
• Contact between neighboring cultures facilitated the rise of plant and animal cultivation globally.

Animal Production Science

The three main branches of animal agricultural science are:

• Nutrition (E)
• Genetics (G)
• Breeding (including assisted breeding technologies) (G)

These disciplines are pragmatic and represent feasible intervention points in animal production systems.

Genetic Progress in Broilers

• 90% of the improvement in growth rate and final muscle mass over the past half-century is attributed to genetics by selecting on naturally occurring mutations or ‘favorable’ alleles.
• The remaining improvement is related to better management, including nutrition.
• Dramatic improvement is due to:
  • Short generation time
  • Highly heritable traits
  • Intensive industries with fine control over breeding
  • Good phenotype records and knowledge of pedigree
  • The ability of a male to sire many offspring, allowing rapid transmission of elite genetics through an entire herd or flock

Breeding

• Breeding, including assisted reproductive technologies in addition to natural mating, is the vehicle through which genetic improvement is made.
• The aim is to pick the best parents to bring together favorable alleles (gene variants) as quickly as possible (in as few generations as possible).
• The key question is: How do we pick the best parents?

Selecting on Phenotype Only

Selecting parents purely on phenotype may:

• Overlook parents with a poor phenotype but great genetics.
• Choose parents with great phenotypes but more modest genetics.
• Require a costly and/or lengthy phenotyping exercise to test the parents for merit.
• Make it difficult to assess merit in cases where the parent does not express the phenotype.

Use of Traditional Pedigree

• Knowing the breeding history of animals is important.
• Phenotypes such as milk yield can be associated with pedigree.
• If many daughters of a particular dairy bull are very good milkers, the bull will be awarded a high Estimated Breeding Value (EBV).
• The bull contributes 50% of the genetics and can carry the favorable alleles for milk production even though he does not express the phenotype.

Pedigree

• Pedigrees are visual ‘tree-like’ representations that demonstrate how alleles are passed down generations in the context of phenotypes of interest.
• Males are represented as squares, and individuals affected by a disease (binary phenotype) are colored black.
• These diagrams show which parent transmits desirable or deleterious alleles.

Quantitative Trait Loci (QTL)

• A locus (or segment of DNA) that correlates with variation of a (continuous) quantitative trait in the phenotype of a population.
• QTL are mapped by identifying which molecular markers (typically biallelic SNP) correlate with the expression of a trait.
• The number of QTL explaining variation in a trait indicates its genetic architecture.

Genome Wide Association Study (GWAS)

• A ‘Manhattan plot’ expresses the association between SNP and a quantitative trait.
• The peaks in the plot are Quantitative Trait Loci (QTL).

Single Nucleotide Polymorphism (SNP)

• Variation that occurs at a specific nucleotide position (locus) in the genome.
• Each variant must be present in a population to an appreciable degree (>1%).
• For example, some individuals may have a C at a given locus, but others possess a T. This is a C/T biallelic SNP.
• In the human genome, 600 million SNPs have now been identified:
  • 1 \text{ SNP every } 5 \text{ bp (across the } 3 \text{ billion bp human genome)}

Molecular Genetics

• Technologies such as Single Nucleotide Polymorphism (SNP) genotyping can be used to understand the exact genetic makeup of individuals (or animals) at very high resolution.
• A tissue sample (ear punch, blood, hair) can be submitted for DNA purification and subsequent hybridization to a SNP array.
• Molecular EBVs can then be calculated.
• These have doubled the rate of genetic gain in intensive production industries.
• Molecular genetics allows for more accurate estimation of relationships among animals and detection of known favorable alleles for particular traits responsible for QTL.

SNP Chip

• A DNA SNP chip is a small piece of silicon glass (~1 cm^2) bonded to many ‘oligos.’
• These oligos act like molecular "velcro."
• A computer "reads" which alleles are present in a submitted DNA sample.
• For example, the allele with the ~T~ SNP allele binds to the ~~A oligo, and the allele with the ~C~ SNP allele binds to the ~~G oligo.
• The individual is identified as a C / T heterozygote at this loci.

Advantages of Molecular EBV / DNA Marker Assisted Selection

• Parent-offspring relationships are always 50% (or 0.5) as each offspring receives exactly half of their autosomal material from each parent.
• However, many relationships (e.g., siblings) can deviate from the 0.5 expectation because of meiosis.

SNP Distribution and Biological Influence

• SNPs can range from having little to no effect to having profound effects.
• Mutations likely to influence a phenotype include those that change:
  • Protein coding sequence
  • Promoter sequence
  • Intronic sequence
  • Other changes that influence gene expression, such as manipulation of non-coding RNAs
  • Any change to ‘influential’ molecules
• Examples include Piedmontese and Belgium Blue cattle breeds.

Commercially Important Agricultural Traits

• Usually complex, continuous traits like:
  • Muscle mass
  • Marbling %
  • Feed conversion efficiency
  • Disease resistance
• These vary along a continuous gradient depicted by a bell curve.
• Influenced by many genes of small effect.
• However, there are some simple discrete (or binary) examples, such as horned versus polled cattle.
  • These have a simple genetic architecture, with one or a few gene(s) responsible and follow a Mendelian inheritance pattern.

Punnett Square for Binary Trait Inheritance

• A Punnett square shows a typical test cross.
• Each parent carries two alleles, one of which is contributed through reproduction (via meiosis).
• Using probabilities, one can determine which offspring genotypes the parents can create and their frequencies.
• Green pod color is dominant over yellow for pea pods in contrast to pea seeds, where yellow cotyledon color is dominant over green.

Non-Mendelian Inheritance

In these situations, the proportions of phenotypes observed in the progeny do not match the predicted values:

• Incomplete dominance (e.g., intermediate inheritance of flower pigmentation)
• Co-dominance (e.g., offspring have speckled feathers from black and white parents)
• Genetic linkage (violating the assumption of independent assortment)
• Multiple alleles (e.g., the Agouti locus in dogs has 4 alleles influencing coat color)
• Epistasis (a type of interaction that can stop dominant alleles from expressing their effect)
• Sex-linked inheritance (e.g., color blindness)
• Extranuclear inheritance (e.g., mitochondrial diseases, inborn errors of metabolism)
• Polygenic traits (e.g., human skin color)
• Genomic imprinting (transmissible epigenetic marks during meiosis)

Some questions

• Is there a limit on genetic gain?
• Is there any evidence of progress slowing?
• Which traits might we select in the future?
• How might GMO technology inform future genetics?
  • CRISPR technology
  • Regulatory framework
  • Consumer acceptance / ethical framework

An Animal GMO in the Food Chain (2015)

• AquAdvantage Salmon:
  • Atlantic salmon with a growth hormone gene from Chinook salmon to accelerate growth, and a fragment of DNA from ocean pout to help activate the Chinook gene.

Domestic Animal Traits

• Interesting coat patterns, floppy ears, curly tails, late maturation, and other ‘cute’ features are commonly observed but not always deliberately selected for.
• This raises the question of their origin.

The Domestication Syndrome

• Weakened ear cartilages leading to floppy ears
• Shortened snout
• Reduced odontoblasts leading to reduced tooth size
• Reduced brain size
• Changes in melanocytes leading to pigmentation changes in coat
• Cartilages of tail shortening and curling
• Coat pigmentation changes appear as a consequence of selecting on tameness.