[haleaton]

Illumina HumanOmni5-Quad

It provides 4.3 million + up to 500,000 custom markers and that the data set used for marker selection was the 1000 Genomes Dec 2010 release. Y coverage is tiny, but can the 500K customer markers be assigned to Y-DNA--particularly 1k Genome SNPs and other SNPs in FTNDA SnpInfo?

[KerryOdair]

It provides 4.3 million + up to 500,000 custom markers and that the data set used for marker selection was the 1000 Genomes Dec 2010 release. Y coverage is tiny, but can the 500K customer markers be assigned to Y-DNA--particularly 1k Genome SNPs and other SNPs in FTNDA SnpInfo?

Hello,

I am posting a reply from Ray Banks at DNA-FORUMS who has been a wonderful contributor to the mining of the Y data from the 1K genome project. I see that you have been to that board as well. I put his reply below for others to see that best answers your question.

There is a strong possibility for the next step beyond 23andme with a custom chip with y snp's on it. I am still holding out for full sequencing. As Ray has suggested 30x coverage and read lengths longer than 100K BP would probably be necessary. Right now we are using brute force with numbers of people to look at the data. Sequenced data in libraries using the full power of computing would be a much better situation. Will brute force with enough Y snp's to justify a chip design before sequencing becomes cheap enough for the man on the street is the question. Isolating the Y and sequencing is a better solution in the long run if the pricing could be justified. We are only talking 60 M BP on Y versus 3 B BP on the genome. Isolation of the Y is the big stumbling block at this point probably not the cost of sequencing.


"I may be in a minority on this, but my impression after extracting SNPs in multiple haplogroups and the perspective from the viewpoint of these haplogroups is that the shared SNPs that have been listed with Z numbers fill in important gaps in the Y tree. As best as I can tell, however, these are primarily SNPs that developed 3000-5000 yrs ago and are thus common enough to be found in the several hundred samples we have examined. Those Z items that define new subgroups -- through persistence of everyone -- will end up as routine tests. The many SNPs that are equivalent to category-defining SNPs are not likely to yield much except for a rare early branch. For example, the new E subgroup in which the Bantus of Kenya have samples is shared with Nigerians. This Kenyan group is dated as having arrived in Kenya with the Bantu expansion about 3000 yrs ago. The new Z723 major branch under L140 in haplogroup G is probably going to be dated to the 3000 yr period because all the various subgroups that might be encompassed by Z723 would be that old.

While these Z SNPs are most useful for the population geneticist, the SNPs I think genealogical researchers should be most interested in -- now that the major missing branches are identified -- are the SNPs that occur in a single person. There will be about 5,000 or more of these singletons in the samples. I have found items from recent WTY among them as well as other new SNPs that have not made it into the official trees yet. One of these (L640) I know -- because it matches another man at Family Tree -- will likely define a major subgroup originating 2000 to 3000 yrs ago. Without the confirmatory presence of L640 outside the 1000 Genomes Project, this SNP would not be noticed or qualify for a Z number because it was found in just one person (singleton)in the 1000 Genomes data.

Family Tree's president has given me assurances they will make use of the singletons I have been extracting, but they do not announce new products until they are ready to offer them. So how they might be used would be speculative on my part. These singleton all lack Z numbers

There are multiple ways in which all the new SNPs -- singletons or otherwise -- might be made available:
(1) allow customers to pay the costs of the process of adding a new SNP to the test list
(2) concentrate on singleton sites in a new version of WTY. Those sites with Z numbers in the database at the checked site would be checked automatically based on what I read about this as written by Thomas Krahn.
(4) create an Illumina chip with the perhaps 10,000 Y SNPs identified in the 1000 Genomes Project.
(5) some other product

He has given no hint as to how these new SNPs might be used. But I have been putting in many hours to get these singletons listed. The process is complete for G and Q samples. The process was begun for J this weekend, and all these spreadsheets are linked from the Variants tabs on Greg's spreadsheet. B, C, D and E will probably be finished by the end of next week. E is, I believe, the largest group in the samples.

It seems like the average man's samples has about 15 new SNPs found only in his sample. But this number has varied among haplogroups. It would seem to indicate being more conservative than this that there are about 5000 singletons -- at a minimum.

It is possible that Family Tree will not follow through on what was communicated to me, but the fact that they did not say that they did not think they could make use of the singletons knowing the time commitment needed to extract these and understanding the significance of them offers some encouragement.

There may be 1500 SNPs among the singletons that would represent sizeable subgroups and would qualify as additions to the Y-trees.

I personally see the greatest potential in the Illumina chip concept, but I may not have a firm understanding of all the limitations of the chip or of the ability of any of the labs to implement such a product in a cost-effective manner."

Ray Banks

[haleaton]

Illumina HumanOmni5-Quad

Thanks for posting Ray Banks DNA Forums post--I also posted a link to these important posts there. You are doing important work.

I am new to this, but I was curious what applicability to the Y was the Illumina HumanOmni5-Quad and its 500K custom snps. Its default snps were based on 1K Genomes which seems like a start at Ray's idea in a sense.

I agree there is a value on a focus on Y sequencing that may not be part of current business models focus on immediate medical and monetary metrics.

There is often inherent and hidden value in open source approaches--get the data public and let the community analyze it.

[KerryOdair]

This is why we need sequencing of the Y. The academic community cannot even make up their minds on this issue of STR dating. We need snp dating via sequencing. Most of these studies are using 15 STR's or less in their studies. In our projects we have great numbers of 67 marker tests and people are upgrading to 111. We have better refinement with our databases but we do not have the cross section of a scientific sampling. Y sequencing will establish the tree by snp's. In one company alone there are 213,000 Y dna tests. We are using many testing techniques that are not giving us the complete answer. Hopefully someone will develop the technique for doing the separation process for the Y chromosome for sequencing. If they build the product the people will come and buy.


A new paper by Cristian Capelli and George Busby at Oxford University.

http://www.bbc.co.uk/news/science-environment-14630012#story_continues_1

"A new study deals a blow to the idea that most European men are descended from farmers who migrated from the Near East 5,000-10,000 years ago.

The findings challenge previous research showing that the genetic signature of the farmers displaced that of Europe's indigenous hunters. The latest work leans towards the idea that most of Europe's males trace a line of descent to stone-age hunters.

But the authors say more work is needed to answer this question.

Furthermore, they suggest that some of the markers on the Y chromosome are less reliable than others for estimating the ages of genetic lineages. On these grounds, they argue that current analytical tools are unsuitable for dating the expansion of R-M269. Indeed, Dr Capelli and his team say the problem extends to other studies of Y-chromosome lineages: dates based on the analysis of conventional DNA markers may have been "systematically underestimated", they write in Proceedings B"

[KerryOdair]

Could Atomic Force Microscopy http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135514/

or laser microdissection techniques be viable options for isolating the Y chromosome at a reasonable cost?

[Joann]

chromosome ultrastructure in a single cell: beyond sequencing

Kerry,
Thanks for posting this paper which brings into focus the ultrastructure of a single chromosome from a single cell. And no statistical analysis whatsoever... I should also point out that even here, it is fixed material that is examined. Can't predict whether these techniques could help with gross isolation of Y chromosomes for large-scale sequencing projects.

[KerryOdair]

This is a significant marriage of venture capital. Maybe 23andMe will be the first to offer full genomes that go beyond the scope of what Knome and Illumina provide today.

DNAnexus Raises $15 Million, Teams With Google To Host Massive DNA DatabaseIn addition to the funding, the company is also announcing a key partnership: it’s's teamed with Google to give a long-term home to the Short/Sequence Read Archive (SRA) database. This immense dataset, which spans 400 terabytes at this point, includes publically available whole-genome sequences that scientists can use for research purposes. The data has previously been housed by the government at the NCBI, but federal cuts mean that organization can no longer shoulder the burden, which is where DNA Nexus and Google are stepping in.

http://techcrunch.com/2011/10/12/dnanexus-raises-15-million-teams-with-google-to-host-massive-dna-database/

http://www.marketwatch.com/story/dnanexus-and-google-team-up-to-improve-access-to-vast-public-repository-of-next-generation-dna-sequencing-data-2011-10-12

[KerryOdair]

This is the latest Walk Through the Y Project information from the FTDNA conference October 2011 Houston TX from Thomas Krahn.

http://www.dna-fingerprint.com/static/FTDNA-Conference-2011-WalkThroughY.pdf

[KerryOdair]

This is the latest Walk Through the Y Project information from the FTDNA conference October 2011 Houston TX from Thomas Krahn.

http://www.dna-fingerprint.com/stati...lkThroughY.pdf

This is additional information supplied by Tim Janzen at the conference in regards to Y chromosome testing.

Thomas Krahn summarized the latest Roche 454 sequencer Y chromosome sequencing results. He is doing Y chromosome enrichment of the DNA prior to sequencing so that he can maximize the Y chromosome sequence data from each sequencing run. In his latest run he tested 8 samples, but only 2 came out reasonably well. He plans to reduce the number of beads he uses in the sequencer and he hopes that will improve the quality of his data. In the latest experiment he got about 19,000 reads from one sample, of which about 48% of the reads were from the Y chromosome after Y enrichment. The average read length was in the 400-600 base pair range. Thomas plans to put the latest sequencing results on his FTP server as a downloadable file of about 300 million megabytes of data for Y SNP hunters to review. Thomas plans to continue to work on Y sequencing until he can perfect the sequencing. Thomas said that there are about 20 million base pairs on the Y that are worthwhile sequencing. The first 2 million base pairs on the p arm are pseudoautosomal and thus aren't helpful from a Y SNP search prospective. The palindromic regions also generally don't have many Y SNPs. The new 454 sequencer will allow about 20 times as many bases to be sequenced as can be done with the WTY project currently. Now the WTY results generally include about 400,000 base pairs. Thus Thomas anticipates at least 6-8 million base pairs of the Y chromosome can be sequenced with the new 454 sequencer in the short term and hopefully about 20 million base pairs can be sequenced in the long term.

[KerryOdair]

This is the significant news from the FTDNA admin conference in Houston TX 2012. A paper to be published in the near term about this. Also a link to slides by Thomas Krahn.

Dr. Mike Hammer has been talking about A00, the new most basal clade of the human Y-chromosome phylogeny. Apparently, >338ky old Y-chromosome ancestor for modern humans, at 98% confidence, with most basal clade found in western Cameroon and in African Americans separated by ~500 years from Cameroonian chromosome.

Root of human Y-chromosome phylogeny is now much older than both mtDNA Eve and first modern human fossils.

Slides: http://prezi.com/kz2c-q4b-_m1/a00-on...plogroup-tree/

"A00 on the Y Haplogroup Tree
A new view on African origins from a Y chromosome perspective
by Thomas Krahn on 12 November 2012"

[KerryOdair]

This is a slide presentation by Bonnie Schrack who is the Admin of the A haplogroup study at FTDNA. This is a quote from her on the slides.

"It's awesome to finally be able to discuss our research! I'm not totally free yet, though, until our paper has been submitted to a journal. Mike Hammer would prefer that we not divulge absolutely all the details, but for now, here's a link to my presentation. Soon I'll post the speaking notes, but for now it's just the slides."

http://www.haplogroup-a.com/2012-11_FTDNA-presentation-1a.pdf

Meanwhile, look into Iwo Eleru, Nigeria. See: http://www.bbc.co.uk/news/science-environment-14947363


" Prof Stringer thinks that ancient humans did not die away once they had given rise to modern humans.


They may have continued to live alongside their descendants in Africa, perhaps exchanging genes with them, until more recently than had been thought."

Thomas said that they have once again upgraded their equipment, doubling their capacity again. This gives 4 times the coverage of the original Walk the Y, covering more than 5 million bases. To date, they have run 494 pre-qualified participants and of those, 198 did not find a new SNP.

There are changes coming in how the palindromic region is scored which will change the matches shown. Palindromic mismatches will now be scored as one mutation event, not multiples. Microalleles will able be reported in the next rollout version, expected probably in January. The problem with microalleles is not the display, but the matching routine.

Of importance, there has not been an individual WTY tested from haplogroups B, M, D or S, and we need one. So if you know of anyone, please contact Thomas.

Thomas has put his Powerpoint presentation online at http://www.dna-fingerprint.com/stati...lkThroughY.pdf

[KerryOdair]

This company has been brought to my attention. Maybe we now have the real deal. Can anyone add any further information on this new company and details.

FullGenomes

We are currently offering a one of a kind test—not available elsewhere—that will sequence your FULL Y-DNA chromosome. This is the DNA you inherit from your father, and his father and so on, back in time. It will allow you to determine the exact SNP's and STR's you have and how you are related to other family members and members of your community.

http://www.fullgenomes.com/#

[KerryOdair]

I started this thread in September of 2010 in a quest for Y Chromosome sequencing. I have found a company in this business and I have placed an order to have my Y Chromosome fully sequenced. I am confident that this new test will be the beginning of a new era for citizen science and development of a more precise phylogenic tree.

I am going to have the raw data to work with in any venue that might further my knowledge about my Y heritage.

[krobison]

Have they described what technology they are using to pull the Y? What sort of sample do you submit?

Interesting that someone thinks there is a business to be had here, given the low medical utility of the Y. I'm not objecting to genealogical research, just wondering how big the market will be & if this company can stay afloat.

[KerryOdair]

Have they described what technology they are using to pull the Y? What sort of sample do you submit?

Interesting that someone thinks there is a business to be had here, given the low medical utility of the Y. I'm not objecting to genealogical research, just wondering how big the market will be & if this company can stay afloat.

The sample is saliva. I suggest you go to the FullGenomes website and contact them via their sales representative.

Based on my own personal investigation I am satisfied with this company and placed an order with them. They have passed my litmus test through various sources.

Based on prior posts you have made, you have been skeptical of the market place for this product. It fills a void that is not being addressed by either Familytreedna or the Genographic project. I guess we will see over time how big the market will be. I say big enough.

Everyone will have to make a personal decision on the value of this test for themselves. I am tired of waiting for cheap nanopore sequencing that seems to be more vapor ware than reality these days. I am older and this sequence can happen today not sometime in the unknown future.