National Geographic and Family Tree DNA Announce Geno 2.0

Today we have some news that is incredibly exciting for our citizen scientists and for all those who are interested in determining their ancestral origins through DNA testing. 

National Geographic is entering the next phase of their Genographic Project in partnership with  Family Tree DNA and the genetic genealogy community. Continuing to move toward their goal of mapping the pattern of human genetics, they are introducing the new GenoChip 2.0. This chip is specifically designed for ancestry testing and includes SNPs from autosomal DNA, X-DNA, Y-DNA and mtDNA. The design of the new chip was a collaborative effort between Eran Elhaik of Johns Hopkins, Spencer Wells of National Geographic, Family Tree DNA and Illumina. The testing will be done at FTDNA in Houston.

Dr. Wells explained that "off-the-shelf chips are not good for studying ancestry" for the simple reason that they are skewed in favor of medically relevant SNPs and are not focused on detailed inclusion of the sex chromosomes and the mtDNA. As a result, this team started from scratch choosing SNPs for the Illumina iSelect HD chip platform one and a half years ago. The resulting chip includes approximately 146,000 SNPs, avoiding all known medically relevant markers and exclusively concentrating on ancestry informative ones. This new chip will be used for both the research and the public participation component of the project.

The new funding structure for the project will be announced in September.

[Caution ahead: Some of the following is quite advanced, so if you are new to genetic genealogy, please skip over the unfamiliar portions. I am including as much as I can from my notes for the more advanced in our community who may want specific details.]

BASICS

The Geno 2.0 test will be offered for $199.95 with free shipping within the US on the National Geographic site and will only require a cheek swab. All resulting data will be downloadable. They will begin accepting pre-orders today for a fall shipping date (10/30/12). In the future, orders will  also be accepted through the Family Tree DNA website (no date is set for this option). Although this is not a traditional relative finder matching tool and is not meant to replace Family Finder, it will cluster you to your closest genetic matches and you will be able to send an anonymous email to correspond with them (not functional at launch). These circle clusters will demonstrate how you connect to people one thousand years ago.

Y-DNA SNPs

The chip includes just over 12,000 Y-DNA SNPs. Ten thousand of these are completely unique and have “never been published before”.  First, the team created probes for all of the 862 Y-SNPs from the current YCC 2010 Tree. Next, they contacted research centers all over the world and asked them to provide a list of all the Y-SNPs that they had data mined or discovered, including the L SNPs, the Z SNPs and “private Hammer” SNPs, and created probes for those. Y-SNPs discovered by citizen scientists were also included.

More details:

- Many new terminal branches will be gained and, according to Bennett Greenspan, this will completely replace the deep clade test currently offered by Family Tree DNA.

- Y-SNPs were vetted against Family Tree DNA’s “Walk Through the Y” samples.

- 862 SNPS from YCC 2010 Tree vs. 6,153 SNPs on the New Tree

- About 200 SNPs from 2010 failed with ~160 SNPS from 2010 unconfirmed

- Most failures were at roots such as R, P, A2 and F. Many have synonymous SNPs.

- 115 SNPs from YCC 2010 Current R-Tree vs 550 SNPs on the New R-Tree with ~200 more potential

- 31 SNPs from 2010 failed with 25 more unconfirmed, but in progress

- Rebekah Canada wrote and/or performed comprehensive rewrites of 182 different Y-DNA stories based on  approximately 1000 peer reviewed publications and information from the genetic genealogy community.

- New, updated Y haplogroup maps

mtDNA SNPs

The chip also includes over 3200 unique mtDNA SNPs. They started by creating probes for the 3352 highest frequency mtDNA SNPs from Family Tree DNA and GenBank. According to Elliott Greenspan, the level of difficulty was greatly increased due to variability in mtDNA. It was necessary to create about 31,000 probes to cover all of the variation that can be found in the surrounding flanking regions. Ultimately, they were able to detect about 3200 of those and, as a result, they can determine about 90% of the known haplogroups at this point.  

More details:

- All SNPs were vetted by running known samples.

- Rebekah Canada wrote new and/or performed comprehensive rewrites of 248 different mtDNA stories based on ~1000 peer reviewed publications and information from the genetic genealogy community. 

- New, updated mtDNA haplogroup maps

Autosomal and X-chromosomal SNPs
 

Over 130,000 autosomal SNPs and X-DNA SNPs were chosen

- AIMs harvested from literature

- AIMs identified using two methods

- Contributed by Family Tree DNA

- Identified at Random
 

Ancestry Informative Markers (AIMs) are SNPs that show substantial differences in allele frequency across population groups. Approximately 75,000 AIMs were chosen from approximately 450 populations around the world. About half of these AIMs were collected from about two dozen published papers and the rest were calculated from private and public datasets. Many of these populations datasets had not previously been studied for this purpose, so they used two algorithms to develop new and never before used AIMs: infocalc by Rosenberg and a private algorithm developed by Dr. Elhaik called “AIMsFinder” (PCA approach). Dr. Elhaik personally collected over 300 population datasets from which they had genotype data from thirty thousand to over one million base pairs and did very exhaustive pairwise comparisons between difficult-to-distinguish populations to build a unique database of AIMs. 

They also wanted to address the question of how much interbreeding occurred between modern humans and ancient hominins. Once again, they collected all relevant SNPs from existing literature on the subject and included those on the chip. However, they wanted to go further so they used a novel approach. They identified regions in which modern humans and Neanderthal shared the derived allele where Denisovan and Chimp share the ancestral and then repeated the exercise for derived alleles in Denisovan, but not Neanderthal and Chimp. Ultimately, they collected about 30,000 such SNPs that they feel can help identify interbreeding between ancient hominins and modern humans.

The team also included SNPs from underrepresented populations such as Paleo-Eskimos and Aboriginal Australians. What they call “control SNPs” came from 7,500 random SNPs that have high frequency in the HapMap and 1000 Genome Project. They were included to facilitate future studies on these SNPs and how they distribute in different populations. They excluded a large number of SNPs that had high linkage disequilibrium (LD) in all populations, excluding those found in the Hunter Gatherer and Papuan populations because these are of special interest for future studies. (An interesting side note, when these high LD SNPs are removed from the commercial platform chips, only about half of the total remains.) The team only included SNPs that were confirmed by both HapMaps and 1000 Genomes to reduce the number of erroneous SNPs.

To ensure that the genetic results will not be used for unethical purposes such as political ends, pharmaceutical ventures, etc… all samples are anonymous, no medical or trait data is collected, and all SNPs are non-coding and have no known function. In order to facilitate this process, the team built a huge database that included all SNPs that were known, suspected or implied to have associations with disease or traits. To avoid imputation, they also removed high LD SNPs. They are confident that phenotype cannot be inferred.

More details:

- 23,962 Neanderthal SNPs

- 1,357 Denisovan SNPs

- 12,027 Aboriginal SNPs

- 10,159 Eskimo Saqqaq SNPs

- 998 Chimpanzee SNPs

- 975 X chromosome SNPs (the team is looking for more X chromosome AIMs from citizen scientists)

- 76% of SNPs overlap with Illumina 660k array

- 55% of SNPs overlap with Illumina HumanOmni1-Quad and Express and Affy 6.0

- 40% of SNP overlap with Affy 5.0 and Human Origins Chip

- GenoChip is enriched for Common Alleles

- Heat maps

Summary

All of this adds up to an unprecedented effort by National Geographic and Family Tree DNA to move genetic genealogy in an innovative new direction. This is a very exciting time for all of us citizen scientists since it appears that there is increasing opportunity to contribute to this advancing field and recognition for those who do.

This blog post is really just a start. There will be much more to report in the coming weeks, including a product review. So, be sure and check back!

[Update 12/13/12 - You can see my results here and others here and here.]