List This new paper is a free download at: http://www.biorxiv.org/content/biorxiv/early/2015/12/23/035105.full.pdf "A protein truncating R179X variant in RNF186 confers protection against ulcerative colitis" Manuel A Rivas, et al. I cannot say this is the easiest paper to read (as it appears to have been written by committee !), but the paper discusses the relevance of Loss-of-Function SNPs (LoF). Is this relevant ? Well yes, as 23andMe has included 1,000s of this type of SNP in its specially commisioned V4 chip. However, this paper deals with rs36095412 which is NOT on the 23andMe chip. As for the paper itself, the researchers have shown (to their surprise) that the protein 'truncated' by the mutated SNP is expressed; and the people with the uncommon homozygous-recessive inheritance do not appear to have any particular problems. But whether one should accept that the truncated protein protects against inflammatory bowel disease to a significant degree would seem a little uncertain. Overall, this is an interesting and informative paper, not perhaps because of its findings, but more in its explanation of why 23andMe appears to be getting considerable funding from the pharmaceutical industry. And how each LoF SNP will have to be studied one-by-one. Ian ---------------------------------------------- Abstract We conducted a search for protein truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. We found that a protein truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P = 6.89×10-7, odds ratio (OR) = 0.30). We further demonstrate that the truncated protein is expressed, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization or loss of an essential protein element.

I just visited the FGC website and noticed that they offer some new tests: Whole Genome Sequencing 2x $280 Whole Genome Sequencing 4x $395 Whole Genome Sequencing 10x $725 Whole Genome Sequencing 15x $895 Whole Genome Sequencing 20x $1,200 Whole Genome Sequencing 30x $1,650 Ultimate 100x Whole Genome $5,350 Y Elite 2.0 Sequencing $775 I have several questions about their tests: 1. I wonder how useful 2x results can be? 2. What can be done with a FGS? 3. Is it possible to extract usable data for GedMatch from FGS *in an easy way*? 4. How well is the Y-chromosome covered? It will definitely make a lot of sense if they offered a test with the same width of coverage as the Y Elite but at a lesser depth. For example 10x would be twice as good as 1000 GP and if the price can be reduced to something like $250, it would make sense, especially if you run a private DNA project with many tests and limited funding. -- Best regards, Atanas Kumbarov http://dna.kumbarov.com/

Dear Atanas, I think you raise some good questions. The way I have always thought about whole genome sequencing is that it will complement the current data we are getting from SNP arrays such as the Illumina Omni Express chip. I see whole genome sequencing discovering autosomal variants (SNPs, indels, etc.) that provide additional insight from both a genealogical and/or an anthropological perspective above and beyond what can be learned from phased haplotypes from SNP arrays. I think that we are a ways from using new autosomal variants found in whole genome sequencing data in a meaningful way genealogically and/or an anthropologically. We need a means to readily cluster everyone who has a specific autosomal variant as found during whole genome sequencing. A search could then be undertaken for shared genealogical connections or shared ancestral locations or populations. All of this will need to be done in the context of a large genetic database in which phased autosomal haplotypes are linked to specific ancestors in an integrated worldwide family tree. The accuracy of the results is also highly important. The advantage of doing 20x or higher sequencing is that you can be much more certain about the accuracy of the sequence data than you can with 2x data. I haven't generated a specific SNP panel dataset such as the data found on the Illumina Omni Express chip from whole genome sequencing data before, but I am sure it can be done by people who are experienced at working with whole genome sequencing data. I believe that the coverage on the Y with Full Genomes' whole genome sequencing is the same coverage that you get with the Y Elite 2.0 test. Someone from Full Genomes should be able to verify that. I would like to point out that even Full Genomes' Ultimate 100x Whole Genome is not the Holy Grail in whole genome sequencing because the data is unphased. What we are still waiting for is a company to generate phased whole genome sequencing data with an extremely high level of accuracy. I know that companies are working on this, but so far it has been challenging for the companies to do. Sincerely, Tim Janzen -----Original Message----- From: genealogy-dna-bounces@rootsweb.com [mailto:genealogy-dna-bounces@rootsweb.com] On Behalf Of Atanas Kumbarov via Sent: Tuesday, January 5, 2016 8:59 AM To: genealogy-dna@rootsweb.com Subject: [DNA] Full Genomes Corporation tests I have several questions about their tests: 1. I wonder how useful 2x results can be? 2. What can be done with a FGS? 3. Is it possible to extract usable data for GedMatch from FGS *in an easy way*? 4. How well is the Y-chromosome covered? Best regards, Atanas Kumbarov

I would think that if two relatives both took a FGS, that it just *might* possibly find new changes that the other tests overlook. I thought that the existing atDNA tests look at just the frequently changing spots. But what if you and a relative share a rare change? -----Original Message----- From: Atanas Kumbarov via <genealogy-dna@rootsweb.com> To: genealogy-dna <genealogy-dna@rootsweb.com> Sent: Tue, Jan 5, 2016 8:59 am Subject: [DNA] Full Genomes Corporation tests I just visited the FGC website and noticed that they offer some new tests: Whole Genome Sequencing 2x $280 Whole Genome Sequencing 4x $395 Whole Genome Sequencing 10x $725 Whole Genome Sequencing 15x $895 Whole Genome Sequencing 20x $1,200 Whole Genome Sequencing 30x $1,650 Ultimate 100x Whole Genome $5,350 Y Elite 2.0 Sequencing $775 I have several questions about their tests: 1. I wonder how useful 2x results can be? 2. What can be done with a FGS? 3. Is it possible to extract usable data for GedMatch from FGS *in an easy way*? 4. How well is the Y-chromosome covered? It will definitely make a lot of sense if they offered a test with the same width of coverage as the Y Elite but at a lesser depth. For example 10x would be twice as good as 1000 GP and if the price can be reduced to something like $250, it would make sense, especially if you run a private DNA project with many tests and limited funding. -- Best regards, Atanas Kumbarov http://dna.kumbarov.com/ ------------------------------- To unsubscribe from the list, please send an email to GENEALOGY-DNA-request@rootsweb.com with the word 'unsubscribe' without the quotes in the subject and the body of the message

Dear Atanas, Justin Loe from FullGenomes just posted the information below on another list: "As mentioned earlier, these are our beta results for 1x coverage: Mapped Y coverage 30x 22,856,938 10x 22,025,697 4x 17,678,170 2x 13,755,442 Average Callable Loci 30x 14,558,001 10x 8,046,540 4x 1,050,996 2x 349,397 Y Elite 2.0: 14,000,000 Callable Loci approximately on average" This helps provide clearer data for your last question than I was able to do in my earlier response. It thus appears that one needs to order at least the 30x whole genome sequence from FullGenomes to get the same number of callable Y chromosome loci as you can get from the Y Elite 2.0 test. Sincerely, Tim Janzen -----Original Message----- From: genealogy-dna-bounces@rootsweb.com [mailto:genealogy-dna-bounces@rootsweb.com] On Behalf Of Atanas Kumbarov via Sent: Tuesday, January 5, 2016 8:59 AM To: genealogy-dna@rootsweb.com Subject: [DNA] Full Genomes Corporation tests I have several questions about their tests: 1. I wonder how useful 2x results can be? 2. What can be done with a FGS? 3. Is it possible to extract usable data for GedMatch from FGS *in an easy way*? 4. How well is the Y-chromosome covered? Best regards, Atanas Kumbarov