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Questions Abound about 23andMe's Ancestry Testing Business at RootsTech Conference

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The term 'consumer genomics' may have a catch-all ring to it, but for the time being it means ancestry testing and genetic genealogy, including for companies such as 23andMe, which built its business on relaying both personal health information and ancestral information back to clients.

That changed in December, when the Mountain View, Calif.-based company suspended the personal health segment of its offering after the US Food and Drug Administration sent it a letter ordering it to cease marketing the service because of concerns about how that information was being used by 23andMe customers.

23andMe now competes in the same genotyping-array-based autosomal DNA testing market as companies that cater specifically to those interested in ancestry testing, such as Gene by Gene's Family Tree DNA business and online genealogy firm Ancestry.com, among others.

While 23andMe was often lauded as having the most comprehensive array on the market — containing more than 950,000 markers, in contrast to approximately 750,000-marker arrays used by rivals — the firm recently adopted a custom chip that contains around 650,000 markers. Because the chip is the fourth that 23andMe has used to date, it is referred to as "version 4" by those familiar with it.

And, according to some genetic genealogists, the timing of the FDA letter and the introduction of the version 4 chip may be costing 23andMe customers in the ancestry testing market, the only market it currently serves.

Ancestry testingcustomers often transfer their data into other databases, such as Family Tree DNA's Family Finder, in order to match with potential relatives who have tested using other services. But since data from 23andMe's version 4 chip is no longer compatible with the data from arrays used by other firms, customers who tested on the newest version of the array are unable to do that.

"We used to recommend testing at 23andMe first, and then transferring the data to Family Tree DNA, and we can't do that anymore," said CeCe Moore, a genetic genealogist and author of the popular blog, Your Genetic Genealogist. "Now, a lot of people are opting to test at AncestryDNA and then transfer the data to Family Tree DNA. And because 23andMe doesn't have that capability right now they are losing a lot of sales."

Moore spoke to BioArray News at the annual RootsTech conference, held in Salt Lake City earlier this month. During the conference, Moore's colleague from the Institute for Genetic Genealogy, Tim Janzen, also commented that he perceived that the suspension of personal health interpretations, and possibly the introduction of the version 4 chip, had led to a decline in 23andMe kit sales.

"The number of matches I am getting through 23andMe has dropped," Janzen told BioArray News at the conference. "Prior to November, I was getting about 50 matches a week, and now I am getting between 10 and 15 a week," he said.

23andMe spokesperson Catherine Afarian confirmed this week that the firm has indeed seen sales slow since November.

"I can confirm that our sales have been impacted by the November 22, 2013, warning letter issued by the FDA," Afarian told BioArray News. "We cannot provide more detail given the active regulatory review process," she said. "Our goal is to work with the FDA in a manner that demonstrates the benefits of testing for individuals and the validity of the science that underlies our service."

23andMe's health focus may also be costing the firm some business in the ancestry testing market because of the perception that its version 4 chip is more focused on health-related SNPs than its previous arrays.

"My impression as an independent observer is that the chip was developed to maximize the medically informative SNPs and I don't think that there was enough thought given to the negative impact that reducing the SNP count might have on our market," said Moore. "We may be a minority, but we are a very vocal minority, and we are the ones promoting their test to other people," she said. Moore added that she and other genetic genealogists have expressed their concerns to 23andMe about this issue, "but I am sure they invested a lot of resources into developing that chip, so it may not be an easy fix."

"It would have been helpful to the genetic genealogy community if 23andMe would have added to the version 4 chip the most important Y chromosome SNPs that have been discovered … since the version 3 chip was developed," said Janzen. "This would have allowed 23andMe to determine the subclade of the males taking the 23andMe test at a higher level of specificity than was possible with the version 3 chip," he said.

Afarian said that 23andMe optimized its chip "for all the areas of our business – health, yes, but we optimize for ancestry and our research efforts too." She added, "Our chip is now 100 percent custom-curated by 23andMe scientists to target the specific locations in the genome known to be informative for ancestry, health, or that are of interest for research."

Janzen noted that it is possible that any drop in sales related to the introduction of version 4, could be offset by the fact that the array may be cheaper to produce and process, and may lead to reduced data storage and computational needs for 23andMe.

"Any serious genetic genealogist will want to be tested at 23andMe in any case so that they can find matches in the 23andMe database," he added.

Measure twice, cut once

A central player in the discussion over 23andMe's new chip is Family Tree DNA. Unlike competitors in the consumer genomics space, like Ancestry.com, National Geographic's Genographic Project, or ScotlandsDNA, Family Tree DNA allows users to upload their data to its database, allowing, say, 23andMe and AncestryDNA customers to liaise with Family Tree DNA customers in the same online environment.

Given the compatibility between the firms' chips, Family Tree DNA was able to accept 23andMe data uploads in the past. However, 23andMe's version 4 chip contains fewer markers than Family Tree DNA's array, meaning that the firm would have to impute data to make up for the gaps in coverage between the chips. And imputation, according to Gene by Gene CEO Bennett Greenspan, can be problematic.

"We are very concerned about taking data without hundreds and hundreds of thousands of data points and providing you with an answer," Greenspan said during a roundtable on genetic genealogy at RootsTech. "We think the compatibility between the chip we are using with Illumina and their new chip will require a lot of imputation, and imputation gives you an opportunity to make mistakes, and once you get down the generations with autosomal DNA, then it gets a little loosey-goosey anyway," he said.

According to Greenspan, Family Tree DNA has "a lot of things on our engineering plate at the moment," and it is "not trivial" to develop the bioinformatic tools to establish compatibility between 23andMe's new array and Family Tree DNA's chip. If it is even doable, the company will need to troubleshoot any resulting service before offering to its customers, he said. "To use the tailor's expression," said Greenspan, "we want to measure twice and cut once."

While there was plenty of discussion of 23andMe's ancestry testing service at RootsTech, there seemed to be some consensus that the consumer genomics firm offers some of the best ancestry analysis tools on the market. Genetic genealogist Kitty Cooper in particular cited the ability of 23andMe customers to compare matching chromosomal segments with multiple participants, a feature still absent from other providers' offerings.

"We do have some of the most scientifically rigorous tools for ancestry analysis that are currently available," said Afarian, adding, "We'll continue to look for ways to enhance existing tools and develop new ones for the ancestry community."