Thursday, December 20, 2012

Lower Prices, More Genotypes

I was really happy to see that 23andMe has lowered prices in an effort to genotype 1,000,000 people. Luckily the effective population size (a measure of genetic diversity) is much smaller in cattle breeds, so many fewer animals are needed to design genomic selection programs!

But, in an effort to increase the number of animals in its training population with high accuracy EPDs (genetic predictions), the American Hereford Association is offering a cost-sharing program to offset DNA test cost for breeders. If I was a breeder with a bull who meet the AHA's criteria, I would be jumping at the opportunity. (And, if I can scrounge up the money during the holidays, I will be taking advantage of 23andMe's deal!)

See message from the AHA below. 


High Accuracy Bulls Sought, Cost-Share Option Available

During the American Hereford Association (AHA) Board meeting the Board discussed its continued commitment to DNA testing more high accuracy sires. Hereford breeders who have a bull that does not have a genomic-enhanced expected progeny difference (GE-EPD), has a weaning weight accuracy of better than .50 and was born in 2001 or after, can contact Toni Shapiro at the AHA office, and the AHA will pay $40 of the fees to have the bull DNA tested.
A list of high-use Hereford sires that the Association would like tested has been generated. To see if a bull you own is on that list, contact Jack Ward, AHA chief operating officer and director of breed improvement, at jward@hereford.org or at 816-842-3757.
For more about Hereford DNA testing visit the Hereford YouTube channel orHereford.org (PDF). 

Beef Genomic Selection strategies

This past summer Hereford, Simmental, and Limousin breed associations announced genomic-enhanced EPD programs, following the lead of the Angus Association.  Two strategies have emerged, which I will call the commercial model and the genotype model.

The Commercial Model
In the commercial model, cattle producers send hair or other tissue samples to their breed association.  The association enters the identification information into its database, and sends the tissue sample to the DNA testing company (typically Pfizer or GeneSeek).  The DNA testing company extracts DNA from the tissue and runs a SNP assay.  These SNP tests contain hundreds or thousands of SNP markers, depending on the company.  The company then computes molecular breeding values (MBVs) based on the animals SNP genotypes.  A MBV is an estimated breeding value based solely on molecular markers.  The company then returns the MBVs to the breed association.  The breed association then uses these MBVs as an indicator trait to predict more accurate EPDs (see also Table 2 of "The Future is Here!").  The American Angus Association is currently using the commercial model.

The Genotype Model
This past summer the American Hereford Association, in partnership with the NBCEC, became the first breed association to develop and market its own genomic selection test. This means that the breed association manages the phenotypes and genotypes.  The process is as follows. Breeders let the breed association know they would like to test an animal (note, the animal must have a registration number).  The association then generates the test form with tracking bar code, and the breeder sends tissue samples and the test form to GeneSeek. This is when the process is fundamentally different.  GeneSeek then returns genotypes from the Bovine50K assay to the breed association, rather than a molecular breeding value. The breed association and the breeders now own more of the data associated with the genomic predictions. This also allows the American Hereford Association to routinely retrain and improve their genomic prediction models as increasing numbers of animals are genotyped. The North American Limousin Foundation and the American Simmental Association also have access to their genotypes.

For another take on the different paradigms in genomic selection strategies, see this video by Matt Spangler.

*Note: Article was updated on September 20th, 2013 to reflect that Limousin and Simmental have access to their genotypes resulting from Neogen's purchase of Igenity.

Friday, November 9, 2012

Birth Date Selection Mapping

My advisor, Jerry Taylor, and I recently developed and published in BMC Genomics a new method to identify ongoing selection on complex or quantitative traits (A novel analytical method, Birth Date Selection Mapping, detects response of the Angus (Bos taurus) genome to selection on complex traits). Previous methods identify selection which has reached completion (or nearly reach completion) on novel mutations affecting Mendelian traits. A well known example of this type of selection is the adaptation of human populations to digest milk as adults. But, these sweeping selection events are the exception.
Blue lines represent hypothetical variants that are drifting randomly through a population with an effective size of 100.  Red lines represent hypothetical variants that are under strong selection. Drifting variants are not associated with birth date. Selected variants change in frequency over time and are strong predictors of birth date. We utilize this fact to identify selected regions of the genome.
Selection often acts in an incremental fashion on variants already present in populations, and this selection is often on complex traits influenced by a large number of genes. By analyzing birth date as the dependent variable in a genome-wide association analysis our method is able to identify these more subtle selection responses.


Bull born in 1956
In our BMC Genomics paper we analyzed 3,570 Angus animals born from 1955 to 2008.  Using our new method we identified regions containing variants in the Angus genome that changed in frequency due to selection.  We estimate that 2% of the genome is under strong selection pressure and another 80% of the genome is under weaker selection pressure.
Bull born in 2007
We were able to show that weaning weight was the trait under the strongest selection pressure. Milk, intramuscular fat, and calving ease were also under strong selection pressure. Angus breeders have been able  to increase growth traits while also decreasing the incidence of birthing problems (dystocia) by changing the shape of cattle.  As seen in the two bulls above, modern Angus cattle have more refined heads and smoother, smaller shoulders.

Our results also suggests that the immune system is under selection in cattle. On multiple chromosomes, genes with immune functions where identified as responding to selection. Selection favors cattle that survive and reproduce by keeping pace in an "evolutionary arms race" with rapidly evolving pathogens that infect cattle.  This result has been replicated in 4 additional cattle breeds, and I will be presenting this new research at the Cattle/Sheep/Goat workshop at the Plant and Animal Genome XXI Conference in January, 2013.

Friday, September 14, 2012

Doctor Bovine Genome
or: How I Learned to Stop Worrying and Fix the Assembly

I know, this is a very strange title for a post.  More about that later...

USDA Fellowship

In this post I want to introduce you to part of my day-to-day research.  In August of this year, I was awarded a USDA NIFA Postdoctoral Fellowship.  I was awarded this fellowship for two reasons: to prepare to become a leader in agricultural science and to complete a specific project.  My project is reassembly of the bovine reference genome sequence.

Motivation: Why are we reassembling the bovine genome?

The completion of the draft human genome sequence was announced to much fanfare in 2000.  But, the work of finishing the human genome still continues.  Two versions of the bovine reference sequence, by the Baylor College of Medicine and the University of Maryland, were published in 2009.  At that time the bovine genomics community began discussing how to improve the draft assembly.  Key players suggested that more sequence data on L1 Dominette 01449, the cow on whom the reference sequence is based, would be the best step to improve the assembly.  Subsequently, this additional data was generated.
Hereford cow
L1 Dominette 01449, courtesy Michael MacNeil, USDA

My Experience

Scientists who work with draft genomes know to watch for errors in the reference.  As part of my Ph.D. training, I did a local assembly of a 400,000 base pair region to identify a DNA rearrangement which controls a phenotypic trait.  When I finished, the Baylor reference, Maryland reference, and my assembly had numerous disagreements about the sequence of this region.  I decided that if I was going to be successful in identifying variants which underlie phenotypic variation, I was going to need a better reference.


Volunteering  



Last winter, I wrote a USDA NIFA Postdoctoral Fellowship proposal in which I volunteered to take the existing data that was waiting to be analyzed and lead the reassembly of the bovine reference genome sequence.  Leaders in the bovine genomics community supported my application and agreed to share sequence data for the reassembly effort. Fortunately, Uncle Sam accepted my proposal and will be paying my salary for the next two years.


In Conclusion, Dr. Strangelove

The title of this post is inspired by one of my advisor's favorite movies. And just like a doomsday device, the value of a scientific project is lost if you don't tell the world! Check back here for more updates about the progress of the bovine genome reassembly.

*Finally, two disclaimers.  First, I don't consider myself "Doctor Bovine Genome", I simply needed a catchy title.  Second, I don't know of any similarities between myself and Dr. Strangelove.  If you know of any, feel free to leave them in the comments section.  Enjoy!

Friday, September 7, 2012

Take Care When Collecting Hair Samples

I received this reminder from the American Hereford Association this morning:

Take Care When Collecting DNA

GeneSeek Inc., Lincoln, Neb., is the new American Hereford Association (AHA) DNA lab (learn more). The switch has not been without its challenges and one of those is that the new technology, SNP based, requires a lot more DNA than the previous technology. In other words, we have had several requests that have not fully been reported because the lab will not have enough DNA for each of the tests. Assays are different for the abnormalities, parent verification, horned/polled and 50k GE-EPD.
The bottom line is the lab needs a minimum of 80 hairs with the follicles and the best place to pull is right above the switch on the tail. This technology is also very sensitive to contamination due to pour-ons and other insecticides, so please keep that in mind. If you have any questions, contact Jack Ward at 816-842-3757.
SNP assays require large amounts of high quality DNA. From GENESEEK's instructions, the amount of hair should be about the thickness of a ball point pin.  For more information on collecting tissues for DNA extraction, check out this guide from MU Extension (website or pdf).

Saturday, August 18, 2012

Asking the Right Questions...

Drovers Cattle Network recently shared this video in which they discussed the recent changes at Igenity.  The conversation continued by discussing strategies (and products) to reduce risk and select the best replacement heifers and cows during drought conditions.  So, that got me interested in the products referred to by Dr. Jim Gibb.  A quick search lead me to here and here on Igenity's website.  At the end of the second link it says:
Have more questions?Let an expert give you the inside information — igenity.support@neogen.com
So, what questions should beef producers be asking?  As we previously discussed, some beef genomic technologies return valuable information (tests for traits with genes of large effect, genomic selection) and some do not (gene tests predicting a complex trait with a small number of markers).  Following are some questions (and suggested actions) to get you started:

1. Has the test been validated by the NCBEC?  
    (If it is a new test the process of NCBEC validation has likely not been completed.  Or, better yet, visit NBCEC's site before making a phone call or sending an email.)
2. What were the results of the NCBEC validation study?
    (If a validation study has been done and the test was not validated, don't use it.)
3. Has the test been validated in-house?  What were the results?
4. Approximately how many DNA markers are included in the test?
    (If it is a quantitative or complex trait, most likely, the more the better.)
5. What breeds and populations were used in the design and validation of this test?
    (If the trait is complex and the breed (or a closely related breed) you use is not in the training or validation set, I would not purchase the test.)
6. How much of the trait's variation is explained by the test?
    (Obviously, the more the better.)

Do you have additional questions you think beef producers should be asking?
Please leave them in the comments section.

*Also, similar questions could be asked when finding a Personal Genomics provider.

Tuesday, August 14, 2012

Quality Beef:
A result of reproductive technologies and genetic selection

I recently came upon this post about Cattlemen's Evolution on the Bridging the Cattle Gap blog.  I loved that he explained the link between reproductive technologies and genetic selection.  In addition to the points raised in his post, artificial insemination also increases the selection intensity.  As we use a smaller number of elite sires that are further from the average of the breed or population, genetic change becomes more rapid.

On August 30th 2012, the College of Agriculture, Food and Natural Resources at the University of Missouri will be launching a new program called Quality Beef-By the Numbers.  This program aims to assist commercial cattle operations to realize increased income as a result of utilizing reproductive and genomic technologies.  Previously, progressive cattle operations have not been rewarded for producing a higher quality product.  This program aims to change that situation.  I encourage you to check it out.

Scott Brown, one of the organizers of Quality Beef, recently sat down with Angus Talk to discuss cattle quality, technology, profit, and genetic selection.

*As a side note, Bridging the Cattle Gap explains that evolution is a fact and is happening all around us. As I previously mentioned, I have a publication under review describing the evolution of Angus cattle that I can't wait to share with you in detail.

Tuesday, August 7, 2012

Gene Tests vs Genomic Selection

Two different paradigms have existed regarding the use of DNA markers in animal breeding. The first strategy is gene tests, also referred to as marker assisted selection (MAS).  The second is genomic selection.

Gene Test

Gene tests attempt to predict a trait or breeding value based on the results (genotypes) of a small number of DNA markers. These tests are either developed using a candidate gene approach or from genome-wide analyses.  In a candidate gene approach, a scientist assumes which genes influence a trait and investigates variants within those genes for an association with the trait of interest.  These assumptions can be wrong and a scientist may identify an association by random chance.  In a genome-wide approach, a scientist makes no assumptions about which genes influence the trait, but analyzes markers evenly spaced throughout the genome.

Genomic Selection

In genomic selection, thousands of evenly spaced DNA markers are genotyped in a large population of animals (more than 1,000).  A statistical model is then created which predicts estimated breeding values of an animal based on that animal's genotypes.  Often, these genomic predictions are combined with traditional genetic evaluations to create genomic-enhanced EPDs.   

Gene Test Fall Flat

The first gene test, GeneSTAR, was marketed in 2000.  It tested a single variant in a single gene that was thought to influence marbling.  In the years that followed more gene test were developed.  For simple traits, which are not influenced by the environment and are controlled by a small number of genes, gene tests are highly accurate.  Genetic abnormalities, coat color, and the presence or absence of horns are examples of simple traits.  But, the majority of economically relevant traits are complex.  Complex traits (growth, marbling, calving ease, etc.) are influenced by both the environment and hundreds or thousands of genes.  Typically, these hundreds of genes individually have a small effect on the trait.  Thus, testing a handful of DNA markers will not lead to an accurate prediction of an animal's genetic merit.  The NBCEC reports the results of attempts to validate many of these tests.  For example, the previously mentioned gene test for marbling was not significantly associated with marbling score. The gene tests for meat tenderness are accurate predictors, although the commercialized tests do not appear to be the causal variants.  Except for gene tests for meat tenderness, most of these tests were a poor investment for cattle producers.

Genomic Selection Delivers the Knockout Punch

In 2001 three scientists, Theo Meuwissen, Ben Hayes, and Mike Goddard, proposed a new way to utilized DNA markers in animal breeding (article is here for you scholarly types).  They showed that using genotypes from tens of thousands of DNA markers spread throughout the genome, accurate estimates of genetic merit could be predicted.  Rather than looking at a small number of genes, every single gene in the genome is taken into account by a nearby DNA marker.  Unfortunately, the DNA technology to implement this method in cattle was not available until 2008.  But, since 2008, genomic selection has been implemented by the dairy industry (see popular press articles in Forbes and The Atlantic), and it is starting to gain traction in the beef industry.

Conclusion

So, why was the Angus breeder in my first post skeptical about the use of genomics in animal breeding?  I'm not sure, but I would venture to guess that livestock producers don't realize that there is a major difference between gene tests and genomic selection.  Of course, we will continue to use gene tests for simple traits, especially genetic abnormalities.  But, when predicting quantitative and complex traits, gene tests are out and genomic selection is here to stay.  

Saturday, July 28, 2012

Manuscript submitted

I submitted a manuscript to BMC Genomics this morning.  I can't wait till the manuscript has made it through the peer review process and is published so I can tell you all about it!

Wednesday, July 11, 2012

Accuracy improvement from Genomic-Enhanced EPDs expressed as progeny equivalents

There is a great article in the Drovers CattleNetwork expressing the improved accuracy from genomic-enhanced EPDs in the number of progeny required to see the same increase in accuracy.  The big gain is in yearling weight, where genomic information provided as much information as 20 progeny.  As the article states, most dams will never have this many progeny in a lifetime, and now producers can have that same level of accuracy at birth.

These results are for Pfizer's 50K product.  I would be interested in seeing the results for Igenity's product as well.  I'll talk more about the differences between the two products in a future post.

Monday, July 2, 2012

Better breeding through cow genetics

Welcome to A Steak in Genomics!

A few weeks ago I was fortunate to be featured in a story on KBIA, Better breeding through cow genetics, by Sarah Redohl.  The story began by describing how I became interested in animal genomics.  It continued by explaining the Animal Genomics Group's genomic selection research.  It concluded with a somewhat skeptical assessment of genomic markers by an Angus breeder.

So, I decided to write this blog to inform farmers, ranchers, and scientists about the use of genomic technologies in animal breeding.