Validating Genetic Markers

Transcription

1 Validating Genetic Markers Dick Quaas, Cornell University Mark Thallman, USMARC Alison Van Eenennaam, UC Davis Cooperative Extension Specialist Animal Biotechnology and Genomics

2 OVERVIEW Background Issues with validation NBCEC validation process Location of data/webpage Summary of results to date Where are we going?

3 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.

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

5 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

6 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.

7 Quantitative traits with markers currently commercialized or under development Meat Tenderness Quality Grade (Marbling) Beef Cattle Feed Efficiency Meat Yield Disease Resistance Dairy Form Milk and Milk Component Yield

8 Validation Prior to moving genetic markers from discovery populations to commercialization, it is important to validate their purported effects on the trait of interest in different breeds and environments, and assess them for correlated responses in associated traits

9 Scarcity of independent validation populations... One of the biggest challenges in validation is the scarcity of independent cattle populations with sufficient phenotypic data to assess the association between various traits and newly discovered genetic markers, and this makes it difficult and expensive to do large-scale field evaluations.

10 ...is going to become a bigger problem. As more markers associated with a variety of traits enter the marketplace, it will become increasingly difficult to find independent populations with suitable phenotypes for validation studies. There is a need for the development of large, wellorganized, thoroughly-phenotyped populations for marker validation studies.

11 Tests currently on the US market for qualitative beef traits Name Trait Desired Genotype GeneSTAR Quality Grade **** GeneSTAR Tenderness ****** Igenity Tenderness 5 Tender GENE

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13 NBCEC validation process The genotyping company requests validation of their claims and is responsible for genotyping DNA samples. Ideally analyses included both Bos taurus and Bos indicus reference populations, although such populations with the appropriate phenotypes and all allele frequencies were not readily available. Phenotypic data and DNA were mostly collected as part of the Carcass Merit Project. The NBCEC then performs an analysis to determine whether there is an association between the results of the genetic test and the phenotype for the claimed trait.

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15 GeneSTAR Quality Grade GeneSTAR Quality Grade TG5 + M2 CMP Charolais sires (Angus dams) only (CMP Herefords 99:1 M2 allele freq.) Results Small, nonsignificant effect on marbling Significant effect on % Choice or better Conclusion Modestly effective, primarily due to TG5, Stars aren t equal; TG5 >>>M2

16 Selection for Marbling 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. Vieselmeyer, B. A., R. J. Rasby, B. L. Gwartney, C. R. Calkins, R. A. Stock, and J. A. Gosey Use of expected progeny differences for marbling in beef: I. Production traits. J Anim Sci. 74:

17 Tenderness Marker Summary GeneSTAR Tenderness IGENITY Tendergene Bovigen & Merial each market a 3 SNP marker panel for tenderness 2 identical calpain SNP: CAPN1 316 & 4751 from MARC 1 calpastatin SNP Bovigen: CAST-T1 (Genetic Solutions) Merial: UoG-CAST (U. of Guelph) Validation was carried out on over 1,000 Bos taurus and Bos indicus cattle.

18 Frequencies of favorable alleles Calpastatin SNP (UoG-CAST or T1) Taurus: 60-90% favorable alleles Brahmans: ~40-60% favorable Calpain 316 Taurus: ~20 % favorable (C) Brahmans: ~2% favorable Calpain 4751 Taurus: ~50 % favorable (C) Brahmans: ~5-10% favorable

19 The two 3-SNP tenderness panels are effective About 2.25 lbs difference between best & worst genotypes Should expect lb. by making herd homozygous depending on breed From the perspective of genetic improvement, the beef industry may have the opportunity to make improvement in tenderness by increasing the frequency of the CAPN1 316/4751 C-C haplotype

20 Selection for Tenderness $

21 Ancillary Analyses 4 leptin SNP GHR UASM1, UASM2, exon2fb, A252T Traits analyzed: Carcass wt, REA, Fat thick., YG, Marbling score Results: Leptin SNP not associated with traits; (A252T not polymorphic) GHR associated with REA & YG but favorable allele rare

22 This is a young industry...

23 1954 version of what 'home computers' might look like in 50 years time (i.e. 2004)

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

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

26 Where are we going? As more markers associated with a variety of traits enter the marketplace, it will become increasingly difficult to find independent populations with suitable phenotypes for validation studies. Validation studies can also serve to generate information (size of allelic substitutions in a range of production environments, allele frequencies in different populations and breeds, and effects of genotypes on non-target traits) that is essential for the process of incorporating DNA tests into the national cattle evaluation GE EPD.

27 Questions?