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Marker-Assisted Selection

Marker-Assisted Selection. Alison Van Eenennaam, Ph.D. Cooperative Extension Specialist Animal Biotechnology and Genomics alvaneenennaam@ucdavis.edu http://animalscience.ucdavis.edu/animalbiotech/. Overview. Genetic Markers What is Marker-Assisted Selection (MAS) ?

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Marker-Assisted Selection

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  1. Marker-Assisted Selection Alison Van Eenennaam, Ph.D. Cooperative Extension Specialist Animal Biotechnology and Genomics alvaneenennaam@ucdavis.edu http://animalscience.ucdavis.edu/animalbiotech/ Animal Biotechnology and Genomics Education

  2. Overview • Genetic Markers • What is Marker-Assisted Selection (MAS) ? • Current Traits with Markers • Use of Marker-Assisted Selection • The Future

  3. What is DNA ?

  4. What is a Genetic Marker ? A DNA sequence variation that has been associated with a given trait in one or more populations

  5. What is a SNP ? SNPs = Single nucleotide polymorphisms SNPs are the most common and stable type of DNA marker in cattle and are ideally suited for automated, economical genetic testing (genotyping)

  6. Genotyping Heterozygous bull CACGT CATGT ½ ½ CACGT CATGT

  7. Simple (qualitative) traits • Genotype = phenotype • Gender (XY = male XX = female) • Some genetic diseases • Double muscling • Coat color • Horns • All or nothing

  8. 2 Complex (quantitative) traits Genotype Environment Phenotype

  9. Traditional Genetic Evaluation and EPD-based Selection Selection on EPDs derived from the observable performance of the animal and its relativeshas the effect on increasing the frequency of favorable alleles (and sometimes unfavorable alleles) without knowing the corresponding genes and molecular mechanisms

  10. 77 inches ‘tip to tip’

  11. Commercial companies are now offering DNA markers for use in Marker-Assisted Selection (MAS) for given traits Marker-assisted selection is the process of using the results of DNA testing to assist in the selection of individuals to become parents in the next generation.

  12. Assisted - To give help or support to, especially as a subordinate or supplement; aid Driven - Powered, operated, or controlled; to exert inescapable or coercive pressure on Marker-Assisted Selection (MAS) Marker-Driven Selection (MAD)

  13. Current applications: Marker-assisted selection • Testing for genetic defects e.g. BLAD • Testing for single gene traits e.g. coat color • Marker-assisted selection for multigenic or quantitative traits e.g. tenderness

  14. Yep, looks like none of ‘em were resistant Potential benefits from MAS are greatest for traits that • Are difficult or expensive to measure, • Cannot be measured until late in life or after the animal is dead, • Are not currently selected for because they are not routinely measured, • Have low heritability, • Have undesired correlations with undesirable traits

  15. Traits that are most likely to benefit from MAS(descending order) • Simply inherited genetic defects, • carcass quality and palatability attributes, • fertility and reproductive efficiency, • maintenance requirements • carcass quantity and yield, • milk production and maternal ability, and • growth performance.

  16. Progeny from Angus bulls with high (>.4) and low (< -0.16) EPDs for marbling were compared. 74% of high offspring graded choice versus 47% of low EPD offspring. Selection for Marbling Vieselmeyer, B. A., R. J. Rasby, B. L. Gwartney, C. R. Calkins, R. A. Stock, and J. A. Gosey. 1996. Use of expected progeny differences for marbling in beef: I. Production traits. J Anim Sci. 74:1009-1013.

  17. Selection for Tenderness $

  18. Size of the effect of the marker What proportion of the variation in the trait of interest is attributable to the favorable of the DNA-marker allele ? How can a well-proven bull with a high EPD for a given trait be carrying the “wrong” (unfavorable) marker genotype for the trait ? Genetic progress will be hindered if the presence of two copies of a single marker is used as a litmus test for bull selection Marker-Assisted Selection (MAS)Size of the marker effect

  19. Which would you rather have??? • A bull that is ‘homozygous’ for a positive genetic variant with a trait EPD of +3, or • A bull carrying no copies of that genetic variant with a trait EPD of +3 **

  20. Both are important!! • The ‘homozygous’ bull is a source of favorable form of the genetic variant. Can eventually be used to create homozygous calves • The other bull contributes other favorable genes, which will improve the other genes affecting the trait. • Breeding the marker-associated form of the gene into the bull that has no copies should improve the trait by combining all of the good forms of the genes together in one animal

  21. Frequency of the marker* Marker-Assisted Selection (MAS)Allele frequencies * These are the frequencies in the data analyzed and are not necessarily reflective of any purebred population. http://www.nbcec.org/

  22. Should I use Marker-Assisted Selection ?

  23. The increased economic returns from increasing the allele frequency of the marker or genetic gain in the trait of interest as a result of using the markers must outweigh the cost of genotyping Translation “will marker assisted selection make you money ?” Should I use DNA-based marker-assisted selection in my breeding program?

  24. Should I use DNA-based marker-assisted selection in my breeding program? • How much of the additive genetic variation in the trait of interest does this marker explain in your herd? Translation “the weight a marker is given should be proportional to its effect on the trait”

  25. Make sure you know what your results mean Translation “every individual receives one allele of each marker from each parent – so two is maximum.” Should I use DNA-based marker-assisted selection in my breeding program?      

  26. What form of the marker do you want for your production environment or your breed ? Translation “Make sure you know what it is that you want to select for in your situation” Should I use DNA-based marker-assisted selection in my breeding program?

  27. What are you giving up to use animals that are carrying the marker of interest ? Translation “Selection should focus on more than a single marker associated with a single trait” Should I use DNA-based marker-assisted selection in my breeding program?

  28. Should I use DNA-based marker-assisted selection in my breeding program? • Could good progress in that trait be achieved without the expense of marker assisted selection ? (i.e. just use EPDs) Translation “Although DNA-based markers are relatively new and alluring, they are not a silver bullet.”

  29. Use ALL available information to select animals that stand out in the crowd

  30. MAS is likely to accelerate genetic progress in some traits better than others Too much emphasis on one gene/trait is not desirable Validation and breed-specific allele frequencies Genetic markers will not overcome a poor environment Markers are not a replacement for EPDs Ensure you weigh the cost and benefits of using MAS in your production system just as you would with any other input Things to think about when using marker assisted selection

  31. This is a young industry....

  32. “1954 version of what 'home computers' might look like in 50 years time (i.e. 2004)” Animal Biotechnology and Genomics Education

  33. Wrong Expert Predictions “There is no reason anyone would want a computer in their home.”Ken Olson, president of Digital Equipment Corp. 1977 “I think there's a world market for about five computers” Thomas J. Watson, chairman of the board of IBM. 1943 Animal Biotechnology and Genomics Education

  34. “what escaped their vision was that science might come up with new and different ways of commercializing and using new technologies.”

  35. 30 pairs of chromosomes. Roughly the size of the human genome 3 billion base pairs Human & cattle genomes are 83% identical The entire project will cost ~ $50 million Accelerate gene and marker discovery Bovine genome

  36. 21 8 Backfat Birth weight Weaning wt 9 Behavior Weaning wt 12 Birth weight 14 ADG Backfat Birth weight Carcass wt Weaning weight Yearling weight • Chromosome • 1 Birth weight • Weaning wt. • Hot carcass weight • Polled 2 Marbling Retail product yield Rib eye area Yield grade Weaning weight 4 Tenderness 5 Rib bone Dressing percent Rib fat Birth weight Ovulation Rate Tenderness Weaning weight 15 Tenderness 16 Birth weight 18 Birth weight 19 Ovulation Rate 22 Carcass wt 23 Live weight Weaning wt Carcass wt 29 Tenderness 6 Birth weight 7 Ovulation Rate Trypanotolerance

  37. Future Marker-assisted selection will focus on “sustainable traits” • Product quality • Genetic disease resistance • e.g. mastitis resistance • Residual feed efficiency • Health • Robustness • Adaptability • Stayability

  38. An animal is born and tagged...

  39. a SNP panel run on the DNA.... DNA from uniquely IDed calf will be run through a SNP panel of DNA-markers • unique permanent genetic fingerprint, • genetic tests for markers linked to economically relevant traits, and to • assertain parentage. • Genotype data then stored for future traceback of products derived from that animal, and marker data incorporated into herd and breed EPD calculations.

  40. ...and each animal is then managed according to its unique genetic potential. Results are used to make decisions regarding • Health product needs • Feeding strategies • Markets • Breeding decisions

  41. Marker-Driven Selection (MAD)

  42. Marker-Assisted Selection (MAS)

  43. Questions ?

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