[KerryOdair]

I don't doubt that people will be interested in the challenge, but given that this is a tiny bit of genetic machinery that half the population lacks & seems to have very little useful for the other half, it's hard to see much value beyond tracing histories.

Tracing the history of mankind seems interesting to me and others as well. I would think there are a number of population geneticists who might take exception to your comment. Not only do we have the opportunity to study todays populations but methods are also being developed to sequence ancient DNA as well. How much of our DNA is perhaps archaic DNA from other species of mankind? They are in the process now of sequencing the hobbit people from the Philippines. There are many samples in storage to be tested to give us insights of population makeup from the Iron, Bronze, and earlier ages. With different scientific disciplines many gaps in pre history can be better understood. This is the latest study by Cruciani that just came out today on our E1b1 haplogroup.

http://www.plosone.org/article/slideshow.action?uri=info:doi/10.1371/journal.pone.0016073&imageURI=info:doi/10.1371/journal.pone.0016073.g001

based on this paper : http://www.plosone.org/article/info:...l.pone.0016073

To make these new discoveries he used sequencing of the Y to find these new snp's

Given that thousands of public Y chromosomes will be available in the near future, it's hard to imagine many groups focusing on this -- and if they do there are established methods (as I listed above, plus Fluidigm & RainDance and other PCR approaches) for targeting sequencing.

I am not convinced at this point in time that there are going to be thousands of public Y chromosomes in the near future. This will only happen if the complete genome is sequenced based on whats happening today. That expense is two great I think to accomplish that goal in the near future. Sequencing just the Y could be cost effective enough to get the thousands we are looking for in a public format for all to study.

[krobison]

Wet lab developments could head in two directions--refining methods now used for single cell sequencing to enhance successful single chromosome sequencing. Or improved chromosome isolation methods to collect enough Y chromosome sample for one good sequencing run.

The third is continued advances in and applications of whole genome sequencing.

In all these cases, advances in computational techniques targeted to Y chromosome assembly and annotation is win-win-win and an excellent focus of scientific resources.

I don't doubt that people will be interested in the challenge, but given that this is a tiny bit of genetic machinery that half the population lacks & seems to have very little useful for the other half, it's hard to see much value beyond tracing histories.

Given that thousands of public Y chromosomes will be available in the near future, it's hard to imagine many groups focusing on this -- and if they do there are established methods (as I listed above, plus Fluidigm & RainDance and other PCR approaches) for targeting sequencing.

[Joann]

Interesting

I think it would be very interesting to explore the non-coding regions of the Y, in addition to gene sequence variation, in order to chart ancestry, especially where biological evidence can be aligned with paper evidence obtained from written history.

Perhaps in an extension of the methods discussed above, the whole human Y can be tagged and then separated out from other chromosomes by buoyant density or other physical techniques previously applied to subcellular fractionation. It might be an investment to set up the protocol, but then it should simplify and lower the cost of sequencing.

[krobison]

Unless there is a lot of effort focused on driving the cost down, the cost of separating out a specific chromosome is likely to far exceed the cost of just sequencing the whole mess & sifting out what you want. Groups interested in haplotyping (and it is interesting that another proposed method has not yet been implemented).

If you really wanted to focus on Y, easier way is hybridization capture (e.g. SureSelect, OLink, EZCap). The technology exists now, is easily automatable & doesn't require additional high-capital equipment (such as a flow sorter), but you probably are looking at no less than $1K-$1.5K per Y-chromosome targeted -- IF you can get a lot of orders. Otherwise, it starts looking more like $2-3K per Y-chromosome.

But I'm still very skeptical that a market exists between the current array-based tests ($0.1K) & full genome sequencing ($5K-$12K) for a Y-specific test. Are there really going to be enough people curious about their genetic history who are willing to pay 10X the cost for a bit more resolution? Still, a clever operator could set this up & certainly a research group could access any of the existing service providers to do this.

[KerryOdair]

Haplotyping the Y in most males is VERY easy -- you look for Y sequences. Only in an XYY male would there be any point to applying these new technologies for the Y -- and the expectation there is both Y will be identical.

Exception would be if you are interested in some pseudoautosomal regions where confusion with Y is possible -- but these won't be terribly useful for tracing the male lineage anyway.

Hello Krobison,

I understand your point about psedoautosomal regions and not being terribly useful for tracing the male lineage. When I started this thread it was not clear to me if there were viable methods to separate chromosomes for sequencing from the whole genome without full genome sequencing. Again I am not an expert and have no experience in sequencing machines and there use.

So far I have discovered that methods do exist.

1. The 1000 genomes project is using a method for separating the chromosomes
2. There are flow shorter machines that separate chromosomes.
3. In this article there is Fluorescence activated cell sorting technology
4. Illumina Inc. also uses a process for separating the chromosomes in their whole genome sequencing.

The process for sorting of the chromosomes and sequencing machines are in the market place today. Is there a business model that meets a commercial need that people will pay for that can sustain a viable commercial business? My personal answer to this is yes. I have stated earlier in this thread about the numbers and why people would be interested in this kind of testing.

Let me give you examples of the market place dictating new products. Until companies such as Decodeme and 23andme a genealogy company such as Familytreedna had no interest in autosomal tests on chips. Because of the success in the market place today of the 23andme product Familytreedna has their own chip and test for this now. Ethnoancestry was first to the market place for the testing of individual snp’s. Again the market demand made Familytreedna create products for this kind of testing.

I believe that sequencing companies today are so focused on health issues, animal husbandry, and agriculture advances in genome testing that the market place I describe is not even given consideration. It may be niche market. But I think it is a moneymaking niche market not on the scale of these other markets but still a large market in its own right.

I have seen no indication as of yet that sequencing the Y would fall under the regulations of the CLIA certification at this point in time. Just a side note, I have had a telephone conversation with an Associate at Illumina Inc. who will get back to me after the new year when he has had time to discuss this idea with his company. They have not thrown me under the bus as of yet with this concept.

In a perfect world it would be a swab or spit test for the sample. If it requires blood for the process we can live with that. We must first get the sequence. Then the second part to this equation is the library and other software to complement and compare the results.

[krobison]

Haplotyping the Y in most males is VERY easy -- you look for Y sequences. Only in an XYY male would there be any point to applying these new technologies for the Y -- and the expectation there is both Y will be identical.

Exception would be if you are interested in some pseudoautosomal regions where confusion with Y is possible -- but these won't be terribly useful for tracing the male lineage anyway.

[KerryOdair]

DNA tags let us sequence the genome from a single parent

Three researchers at Stanford, Hong Yang, Xi Chen, and Wing Hung Wong, have developed a way to piece sequence fragments back into the discrete chromosomes from whence they came. They call it Phase-Seq, because now the genomic sequences are phased.

First they adapted Fluorescence Activated Cell Sorting technology to isolate single chromosomes based on their unique signatures when stained with certain dyes. Once they isolated a chromosome—in this case, chromosome 19—they chopped them into small fragments, as usual. But then they added a chromosome-specific tag to each fragment. After sequencing the fragments, they used the tags to reconstruct the separate maternal and paternal haploid genome sequences.

Link to article:

http://arstechnica.com/science/news/2010/12/phase-seq-can-sequence-our-two-haploid-genomes.ars

Full Article:

http://www.pnas.org/content/early/2010/12/14/1016725108.full.pdf

[Joann]

Y-specific

Wet lab developments could head in two directions--refining methods now used for single cell sequencing to enhance successful single chromosome sequencing. Or improved chromosome isolation methods to collect enough Y chromosome sample for one good sequencing run.

The third is continued advances in and applications of whole genome sequencing.

In all these cases, advances in computational techniques targeted to Y chromosome assembly and annotation is win-win-win and an excellent focus of scientific resources.

[KerryOdair]

This looks very interesting for isolating the Y chromosome for sequencing.

Now two teams have devised ways to determine these groupings—known as the haplotype—in an individual. Stephen Quake and collaborators at Stanford University developed a way to physically separate the chromosome pairs and sequence each strand of DNA individually. Jay Shendure and colleagues at the University of Washington in Seattle sequenced DNA from single chromosomes in specially selected pools and used this information to piece together the genome. Both projects were published this week in Nature Biotechnology.

http://www.technologyreview.com/biomedicine/26973/

This method has been looked at by Thomas Krahn at Familytreedna. These are his remarks regarding this process. I was hoping for a more positive response than this. Still looking for more comments and solutions in this forum.

Thanks for your notification.

"Yes, it is possible to separate single chromosomes with this technology or also with an instrument called flow sorter.
This technology has been used extensively during the Human Genome Project to make sure that the reads are mapped on the correct chromosome.

However this technology requires the generation of cell lines, so swabs are out and we'd need to collect fresh blood.
Then if we only have a single chromosome it is difficult to get the complete chromosome sequence amplified up to run a sequencing chemistry on it.
Likely there will be multiple gaps and we'd need to sequence several single chromosome isolates to get the complete sequence.
All in all this is quite expensive and I'm not sure if it will ever reach a point when it can be marketed commercially.
However it's good that people at least try to find solutions. We have considered flow sorting before, but we've excluded it because of the cost factor."

Thomas

[KerryOdair]

Sequencing a Single Chromosome

This looks very interesting for isolating the Y chromosome for sequencing.

Now two teams have devised ways to determine these groupings—known as the haplotype—in an individual. Stephen Quake and collaborators at Stanford University developed a way to physically separate the chromosome pairs and sequence each strand of DNA individually. Jay Shendure and colleagues at the University of Washington in Seattle sequenced DNA from single chromosomes in specially selected pools and used this information to piece together the genome. Both projects were published this week in Nature Biotechnology.

http://www.technologyreview.com/biomedicine/26973/

[KerryOdair]

Top Ten Innovations 2010
Innovative products that have the life science community buzzing.

Pacbio named #1 innovation for products in 2010

The long awaited “third-generation” sequencer from Pacific Biosciences takes first place in this year’s Top 10 Innovations contest. The technology qualifies as belonging to a new era because it’s “the first single-molecule real-time sequencer,” says Stephen Turner, the machine’s coinventor and the company’s chief technology officer, speaking to a packed auditorium at this year’s American Society of Human Genetics meeting.

Link:

http://www.the-scientist.com/article/display/57835/

[KerryOdair]

Kerry those were really informative posts in this thread.. though could not read them all, but a list of bookmarks for weekend reading!

thanks

Thanks,

Just trying to show whats going on in the Y chromosome world today. Looking forward to see who wins the race in the sequencing of the Y chromosome. I hope someday to be able to track the paternal wanderings of my line in the world. At present its looks like my line is on course to be one of extinction. No other similar surname has my particular haplotype designation at this point in time and my line will daughter out. My paternal journey starts in Egypt and ends in the Pacific Northwest in the U.S. It would be nice to fill in the map along the way to the Pacific ocean. My surname is validated in genealogy to Pennsylvania starting in 1755. So how does this Irish name go from Egypt to the British Isles? I am not sure I have the total story in the U.S. and I certainly do not have any answers between the British Isles to Egypt. Many sequenced Y chromosomes would certainly give a degree of confidence as to how it all came about. It certainly would make a great story to pass on to place a timeline for the locations on the map of the paternal travels over time.

[bioinfosm]

Kerry those were really informative posts in this thread.. though could not read them all, but a list of bookmarks for weekend reading!

thanks

[KerryOdair]

Article on full genome sequencing around the world with maps.

Genomes by the thousand

http://www.nature.com/news/2010/101027/pdf/4671026a.pdf

[KerryOdair]

Presentations from The 6th International Conference on Genetic Genealogy from Familytreedna

Family Finder: Looking Under the Hood

http://gap.familytreedna.com/media/docs/2010-FTDNA-BW.pdf

Family Finder & Population Finder

http://gap.familytreedna.com/media/docs/2010-FTDNA-BCG.pdf

"Inferring Genetic Ancestry: Oppourtunities, Challenges, and Implications"

http://gap.familytreedna.com/media/docs/2010-FTDNA-MK.pdf

IT Roadmap 2010

http://gap.familytreedna.com/media/docs/2010-FTDNA-IT.pdf

Predicting Individual Ancestry Using Genome-wide Genetic Data

http://gap.familytreedna.com/media/docs/2010-FTDNA-MH.pdf

Summarizing and Anticipating the Next Decade with NRY, mtDNA, and Autosomal DNA

http://gap.familytreedna.com/media/docs/2010-FTDNA-DMB.pdf

Walk Through the Y Project

http://gap.familytreedna.com/media/docs/2010-FTDNA-TK.pdf