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Illumina Capitalizes on Cattle Breeders Adopting SNP Chips for Genomic Selection

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NEW YORK (GenomeWeb) – The availability of custom, low-density arrays for SNP genotyping has fueled widespread adoption by cattle breeders who are using the tools for genomic selection, providing a boost in particular to Illumina's array sales in the ag-biotech market.

Given this continued uptake of SNP chips by breeders, vendors are beginning to envision a future where every animal is genotyped at birth — leading not only to better-informed breeding decisions, but a sustainable source of revenue for chip manufacturers for years to come. 

"Genomic selection is an application that is sweeping this industry," Mike Thompson, director of global sales at San Diego-based Illumina, told GenomeWeb. He noted that the company's BovineLD Genotyping BeadChip in particular has spurred adoption of microarray technology by breeders, especially those who are using the information to select for more productive dairy cattle.

"Conceptually, every cow born could be genotyped, so that the potential value of that information goes with the cow," said Thompson, adding that while not as vertically integrated as the dairy cattle industry, beef cattle breeders have also taken note of the potential for success offered by using SNP chips.

It's a growth trend that continues to propel Illumina in the agricultural space. CEO Jay Flatley remarked on the firm's first quarter earnings call in April that agriculture-related orders rose 20 percent in the first three months of the year driven in part by demand for the BovineLD.

"We continue to see expanded use of selective breeding based on genotype in crop and livestock with a significant number of customers standardizing on Illumina's products," Flatley said.

The firm told GenomeWeb that the cattle genotyping component of the ag-biotech market represents millions of animals. Though it couldn't provide an exact dollar figure, Illumina said that it has a "majority share of the cattle market."

Illumina has catered to the needs of cattle researchers and breeders for years, beginning with the 2008 launch of the BovineSNP50, a product that, in its latest iteration, allows users to survey 54,000 SNPs in a 24-sample-per-chip format, enabling the genome characterization of major dairy and beef cattle breed types. The company in 2010 rolled out the BovineHD DNA Analysis Kit, the most recent version of which allows users to genotype 777,000 SNPs in an eight-sample-per-chip format.

However, it has been Illumina's BovineLD product, which contains 7,000 SNPs and offers users the ability to add up to 80,000 custom markers in a 24-sample format, that has led to mass adoption of the tool by breeders.

"At this point, I think a majority of dairy cattle being genotyped are on assays that start with the BovineLD and add custom content," said Curt Van Tassell, a research geneticist at the US Department of Agriculture's Agricultural Research Service in Beltsville, Md.

Van Tassell worked with Illumina and others to develop the BovineLD prior to the launch of the chip three years ago. Since the chip's introduction, Van Tassell said that the growth rate in animals genotyped on the BovineLD has been "explosive." He cited Council on Dairy Cattle Breeding statistics that show that nearly a million dairy cattle have been genotyped using Illumina chips as of May 2015, the majority of them on the BovineLD or similar, Illumina-made chips offered by agricultural biotechnology service providers like GeneSeek and Zoetis.

Price is playing a key role in this trend, according to Van Tassell, who noted that the current cost for a low-density panel is $46 through the US Holstein Association. This price point, plus the belief that genotyping is worth it, have driven higher adoption, he said.

"All artificial insemination bulls are genotyped before purchase or lease of an animal — every one," said Van Tassell. "Any cow that is considered in an elite mating is now genotyped as a prerequisite of that mating contract," he added. "My sense is that genomic predictions of genetic merit are driving the prices of elite cattle at this point."

While Illumina is providing the products that are used in genomic selection, much of the genotyping is actually being run via service providers. GeneSeek, a Lincoln, Nebraska-based company that is owned by Neogen, currently purchases several hundred thousand BovineLD kits each year to meet its customers' needs, making it "one of the single largest consumers of the product," according to Jeremy Walker, director of GeneSeek's business development and marketing.

GeneSeek also uses the content of the BovineLD as the base for several of its GeneSeek Genomic Profiler arrays. These include the GGP Bovine LD, which relies on approximately 26,000 SNPs, but will be upgrading to 33,000 SNPs in the next few weeks, according to Walker, and the GGP Bovine 150K, which utilizes approximately 150,000 SNPs and retains the Illumina BovineLD base content.

"Both of these arrays utilize Illumina Infinium chemistry and features very carefully selected SNPs for more accurate evaluation of genetic merit, genome-wide selection, comparative genetic studies, and higher-density imputation," said Walker. "These arrays also include comprehensive parentage, [and] disease- and breed-specific production trait-relevant SNPs that have been referenced in hundreds of scientific publications."

Looking to capitalize on growing demand from cattle breeders, GeneSeek is introducing even more products. Last month, it launched Igenity-Select and Igenity-Essential, two microarray-based tests. The first, Igenity-Select, enables the evaluation of a heifer on over 45 select traits for under $40 per test, Walker said. Igenity-Essential's results meantime are "ideal for simple heifer sorting and include an evaluation on 15 essential traits." GeneSeek is also readying a new, higher-density array containing about 200,000 known functional variants in addition to SNP content for whole-genome selection, "further enhancing the tools utilized for applied genomics in animal breeding." This array is expected to be ready later this summer.

In addition to serving as the basis for products offered through service providers, Illumina's BovineLD is also being customized for national and regional breeding programs. Donagh Berry, a statistical geneticist at Teagasc, the Irish Agriculture and Food Development Authority, said that the Irish cattle industry now relies on a platform called the International Dairy & Beef Chip to predict the genetic merit of its cattle.

According to Berry, the panel pairs the base content of the BovineLD with informative SNPs for imputation to higher-density genotypes, as well as SNPs flanking International Society of Animal Genetics-recommended microsatellite markers, as much of Ireland's legacy genetic data is from microsatellite genotyping.

Last year, over 120,000 Irish dairy and beef cattle were genotyped on the array, with most costs paid by breeding companies, individual breeders, and commercial farmers. The uptake of the initiative signified the "belief of commercial farmers in genomic technologies," Berry noted. He added that Ireland plans to genotype more than a million cattle in coming years.

The success of these programs is not in doubt, Berry stressed, stating that based on retrospective analysis, genomic evaluations are up to 54 percent more accurate than the traditional pedigree indexes received by younger animals, and 59 percent of artificial inseminations last year were performed using semen from genotyped bulls.

"The rate of genetic gain nationally has accelerated dramatically and to-date has been worth €16 million ($18 million) profit to the Irish dairy sector," said Berry. "The research cost of developing the genomic predictions including genotyping was €0.4 million." 

Ireland is now planning to launch multi-breed genomic evaluations for beef cattle later this year, and over 100,000 animals will be included in the initial reference population. "It is not inconceivable that in three to five years from now, all cattle born in Ireland will be genotyped at birth," Berry said.

While much of that genotyping will likely be performed using Illumina's chips, breeders are evaluating other technologies, and other companies have positioned themselves to better serve interest from the cattle breeders.

Affymetrix in on the action

Mike Nemzek, vice president of strategic marketing for genotyping at Affymetrix, noted that some customers have expressed frustration with Illumina's various design revisions, and claimed they are moving to the Santa Clara, California-based company's 384-sample format Axiom platform for genotyping animals. Nemzek told GenomeWeb that Affymetrix also offers customers access to its Axiom Bovine Genomic Database, which contains 3 million markers across most breeds that can be selected for custom array design.

According to Nemzek, Affymetrix has developed a number of custom Axiom bovine arrays for specific genomic improvement programs in various countries in recent years. "This has contributed to the high growth rate of the Affymetrix agrigenomics genotyping business, primarily serving customer requirements for high-density genotyping solutions," he said. The company continues to offer its Axiom Genome-Wide Bos 1 Array, which offers 640,000 SNPs covering 10 commercially important cattle breeds.

But microarrays are no longer Affymetrix's sole offering for cattle breeders. Last month, the company paid $15 million in cash to acquire the assets of Eureka Genomics, a developer of low- to mid-plex, high-throughput genotyping assays that use next-generation sequencing platforms for signal readout. Affymetrix concurrently announced a deal with Zoetis, giving the animal health company preferred rights to use Eureka's technologies in its cattle and sheep genotyping services.

"While Affymetrix believes arrays will play a continued prominent role in the bovine testing market, Affymetrix sees the trend of the market migrating to the most appropriate solutions in terms of affordability and content," said Nemzek. "Between Axiom and Eureka Genotyping Solutions, the high-, mid- and low-plex segments of the market are now well served by Affymetrix."

Illumina's Thompson noted that Illumina also offers TruSeq Custom Amplicon next-generation sequencing-based assays targeting panels of less than 3,000 SNPs that should find use in low-plex livestock-related applications such as determination of parentage. Teagasc's Berry said that Ireland is indeed looking into amplicon sequencing as an alternative approach, though any hypothetical switch in technology will be influenced by cost, accuracy of genotype calling, throughput, and repeatability.

"Looking forward, I see continued uptake," Thompson said of the market, adding that the increased adoption of low-density SNP chips for genomic selection will likely expand to other livestock. "I see a very similar continuum across goat, sheep, pigs, even chicken," said Thompson. "These other species are going down the same path, for sure."

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