Illumina BeadChips will power the next stage of National Geographic's Genographic Project, which is mapping the migratory history of humans by analyzing DNA samples from hundreds of thousands of people from around the world.
Spencer Wells, the project's director, told BioArray News this week that the organization has decided to replace its older, PCR-based testing service with an array-based approach because the "field of genetics has moved on significantly" since National Geographic launched the genetic anthropology project, and it "wanted to keep up with the latest technological advances."
Wells also noted that the price of custom genotyping arrays has "dropped significantly" since the project commenced seven years ago, making it possible for National Geographic to apply the technology to anthropological genetics.
National Geographic kicked off the Genographic Project in 2005, offering participants the possibility to learn more about their deep ancestry. Since that time, about 520,000 people have opted to take part. The first version of the test cost $99.95 and allowed male participants to either trace their paternal origins via their Y chromsome or maternal origins by determining the haplotype of their mitochondrial DNA. Female participants were only offered the option of mtDNA testing.
According to Wells, the organization's newer test, dubbed Geno 2.0, will offer more information, and has been designed to maximize coverage of ancestry-informative markers across the entire genome, including those associated with the Y chromosome and mtDNA.
Working together with collaborators at Johns Hopkins University, Family Tree DNA, and Illumina, National Geographic selected ancestry-informative markers from more than 450 worldwide populations, in low linkage disequilibrium, and in non-coding regions, Wells said. As Geno 2.0 is solely focused on ancestral origins, National Geographic "carefully vetted" all markers it ultimately included on the chip against nine databases to remove all known medically relevant SNPs, he said.
"Our commitment to avoiding any medically relevant markers meant that we couldn't use an off-the-shelf chip, most of which are optimized for medical research and not population genetics," he noted.
The result was an Illumina HD iSelect BeadChip containing just over 130,000 autosomal and X-chromosomal SNPs with an average spacing of one SNP per 100 kilobases across 92 percent of the human genome. Of these SNPs, Wells noted that approximately 25,000 are from candidate regions of interbreeding with Neanderthals and Denisovans, hominids who split from humans around 500,000 years ago. National Geographic also included more than 13,000 Y-chromosome SNPs from a variety of sources, "most of which are completely new and have not yet been published," he said.
In addition, the chip contains about 3,200 mtDNA SNPs, which required the inclusion of more than 30,000 markers on the Geno 2.0 chip "due to the high level of polymorphism in the mtDNA genome," Wells said.
National Geographic validated the chip using 1000 Genomes Project samples for autosomal SNPs. Wells said there is 99.5 percent concordance with the 1000 Genomes sequence data, adding that the 0.5 percent discordance is likely because of 1000 Genomes sequencing errors "due to their low coverage."
National Geographic also genotyped about 400 samples with known Y-chromosome and mtDNA sequences to validate the Y and mtDNA SNPs, and has to date genotyped more than 1,000 samples from different populations as part of the validation process.
Wells added that National Geographic and its partners are preparing two publications that discuss the new chip, and have submitted an abstract for the American Society of Human Genetics annual meeting, which will be held in San Francisco in November.
All of that additional data comes with a higher price tag. Geno 2.0 is priced at $199.95, according to National Geographic. The organization is accepting preorders and plans to begin shipping kits to participants in October.
Wells said that testing will be done at Family Tree DNA's Genomics Research Center in Houston. He noted that while Family Tree DNA helped design the chip and is processing the samples, Geno 2.0 remains a National Geographic project.
Arrays are now the main technology for direct-to-consumer ancestry and genealogical testing services, replacing or complementing older, PCR-based offerings.
For instance, Family Tree DNA launched its new service on the Illumina OmniExpress platform last year, with a release price of $289. And, earlier this year, Ancestry.com announced AncestryDNA, a service that is also offered on the Illumina HumanOmniExpress BeadChip platform with a promotional price of $99 for subscribers (BAN 5/29/2012). Both services allow users to share their data online to identify potential relatives and pursue family history research.
Wells said that the difference between Geno 2.0 and the offerings from Family Tree DNA and Ancestry.com is that Geno 2.0 is explicitly for learning about one's ancestral origins, rather than for genealogical purposes. All results are anonymized, and no medical or trait data is collected, as all SNPs are non-coding and have no known function, differentiating the service from 23andMe and DeCode Genetics' offerings.
Another difference is that National Geographic is a nonprofit, and some of the proceeds from Geno 2.0 will help support the organization's Genographic Legacy Fund, which works to conserve and revitalize indigenous cultures around the world. Wells said that of the $45 million that the Genographic Project has grossed since 2005, about $2 million has gone into the fund so far, and the fund will continue to award grants for the foreseeable future.
In addition, Geno 2.0 participants will have the opportunity to choose to register for the Genographic online community to connect with other participants and find shared ancestry, helping to fill in the gaps between what they know about their recent genealogy and their genetic results. This element was not available during the first phase of the Genographic Project.
While National Geographic's project is focused on offering participants the ability to learn more about their deep ancestry, it will support genealogical activities, Wells said.
As it has done to date, National Geographic will allow Genographic participants to transfer their results to Family Tree DNA for free, where they will be able to network with other researchers. Additionally, they can opt to join a National Geographic-sponsored online community of Genographic participants to share their results. And, Wells noted, National Geographic will make participants' results free to them to download.
"Your data belongs to you," he said. "We feel that this is a cornerstone of ethical DTC genetic testing."