Gábor Zsurka, scientist and developer made another upgrade on our favorite human mitochondrial DNA visualization tool, MitoWheel: this time allele frequencies at polymorphic positions are included in the sequence bar in the form of a gray bar above or below a nucleotide representing the number of individuals carrying the SNP.
This is really cool as it is a definite step to turn MitoWheel into a tinkering, engineering, mtDNA hacking tool besides its core science mission:
“This can help you to design reliable PCR primers for the human mitochondrial genome. After all, you don’t want your primer’s 3′-end sitting right on a very frequent polymorphism (risking that under certain conditions you will not be able to amplify a PCR fragment from a subset of individuals).” Source: MitoWheel Blog.
The title question is my million (not billion yet) dollar question for this year. Arthur Levinson is a board member of Google (Apple too) and in his leftover time he is the CEO of the most successful biotech company so far, that’s Genentech. I would be curious to hear about his biotech-related activity as a G board member from my readers even in the form of guesses. Maybe he is teaching biotech classes to Googlers after both Genentech’s and Google’s investment into 23andMe or just sitting around sometimes at the nice cafeterias at the Amphitheatre Parkway, Mountain View and explaining knockout technology to coders.
- compare GenBank’s circa 3000 fully sequenced human mitochondrial genome to the revised Cambridge Reference Sequence mutation by mutation
- by harnessing the power of the colorful group view and using the +, - mutation operators (see detailed introduction) you can dig deeply into phylogenetics and haplogroups
For historical reasons the standard human mitochondrial sequence, the Revised Cambridge Reference Sequence (rCRS) is a reconstruction of a single European individual’s mtDNA and contains several rare alleles. That’s why many times a usual mtDNA sequence alignment must appeal to phylogenetic historical reconstructions. The rCRS nevertheless provides a uniform nucleotide numbering scheme (0-16569). On the other hand, as there are thousands of high-quality, full-length mitochondrial sequences are now available, Robert Carter thought that it is time to construct and analyze a comprehensive human mitochondrial consensus sequence and published his efforts in Nucleic Acid Research, March, 2007: Mitochondrial diversity within modern human populations The sequence itself available as a supplementary material but with the permission of the author I copy it into this post below.
According to Robert Carter:
So far, all feedback has been good. By introducing the idea of “poly-x” sites (see later), I successfully created a technique that avoids all pre-conceived ideas about genetic history. This also allows one to effectively deal with indels, something that many authors have avoided in the mtDNA literature.
Briefly, 827 sequences were used, a master sequence alignment was created in BioEdit and BioPerl was used for all calculations using the rCRS asa template for nucleotide numbering. Read the rest of this entry »
MitoWheel is a cool graphical interface of the circular human mitochondrial genome, which helps the user to get familiar with the mito DNA by searching, clicking and tailoring it. I introduced you MitoWheel a week or so ago, but now you can follow the updates on the MitoWheel Blog.
On the blog you get first-hand information as the posts are written by Gábor Zsurka, main developer himself and occasionally, by me. In his post Cut and Paste the Human Mitochondrial DNA Gábor introduces 2 essential techniques you can easily accomplish with MW:
a., how to search for different mutations and find their functional results on a pop-up window
When I had worked on my MSc thesis in biology on the relation of human mitochondrial mutations and aging the paper I used most frequently was Sequence and organization of the human mitochondrial genome by Anderson et al. published in Nature, 1981. The reason was simple: it is more of a database than a hypothesis driven article with the published 16.569 base pair sequence of the circular human mitochondrial genome (L-strand) containing 37 genes and a bigger non-coding, regulatory region. Throughout my work I had to use it as a basic reference. The sequence is a reconstruction of a single European individual’s mtDNA and contains several rare alleles. Nice figure isn’t it?
I’ve just realized with the help of genomics pioneer and warrior Craig Venter’s recent molecular autobiography Life decoded, that the brilliant two time Nobel laureate, sequencing urfather Frederick Sanger is also a coauthor of the paper. Here comes Venter: Read the rest of this entry »
In my former blog post inF.A.Q. for 23andMe: what if I have mitochondrial DNA from Pa? I meditated on 23andMe’s capability of detecting paternal mitochondrial DNA in their customers’ saliva with their Illumina microarray chips scanning around 2000 mitochondrial single nucleotide variants. Published here the initial answer of the 23andMe Editorial Team to this fairly technical, but nevertheless crucial question with permission granted. Besides, I am happy to report that I am working on a blogterview with one of the key member of 23andMe’s Research Team. Hopefully I’ll be able to get back to you with some first-hand information on the science and technology behind the personal genome service of 23andMe and on how 23andMe can facilitate academic research.
Dear Attila Csordas,
Thank you for your interest in 23andMe’s research mission. The question of paternal inheritance of mtDNA is a fascinating one, and the debate in the literature has continued over the past couple of decades. Currently, there is little evidence for paternal inheritance of mtDNA, outside of isolated individuals. However, the array platform lets us resolve multiple SNP states independently. 23andMe’s technology and throughput may indeed provide a novel way to address the question. We will include the question in our consideration of research projects. In the meantime, here are a couple of articles discussing the subject:
The question is crucial for a personalized genetics company like 23andMe providing Maternal Ancestry Tree service for the customers based on the exclusively maternal inheritance of mitochondrial DNA. As one of my correspondent partner wrote: Read the rest of this entry »
Have you ever asked any important but infrequently asked questions? Have you ever heard about the first personal genome service by the biotech startup 23andMe? Here is an inF.A.Q. addressed to this company:
According to the cool 23andMe genetics educator:
According to the peer review literature this is not necessarily the case and sometimes (rarely I admit) things in your cells can happen otherwise or more scientifically (mitochondrial recombination can occur):
When 23andMe’s Maternal Ancestry Tree service is tracing the genetic path of their customers, the microarray employees are identifying their haplotypes based on the differences in the mitochondrial DNA. The company is using SNPs (single nucleotide variants) unusually both from genes in the compact mitochondrial coding region (around 15.5kb) as well as within the circa 1kb large hypervariable region to give a detailed ancestry assignment. 23andMe examines few thousand places (over 2000 says Mr. Bettinger) on the mitochondrial DNA out of the total 600,000 SNPs.
But.
In the above case the 28 year old man’s blood and muscle differed at 18 positions which allowed assignment of the two sequences to separate European mtDNA haplogroups, H and U5, former being the same as the mother’s haplotype, while the haplotype of the patient’s muscle mtDNA was identical to that of his father’s and uncle’s blood. I wonder whether 23andMe’s Illumina chips can help make things clear in cases like this. (solution: let’s sequence the whole mito genome instead of a couple thousand basepairs). So as the first step in my mission to support the mission of 23andMe to support the mission of academic research I’d like to suggest putting a short tail on the possibility of paternally inherited mtDNA in the cool 23andMe genetics education material. Read the rest of this entry »
“We are all from the same seed” - Kara Swisher summarizes what she heard from Linda Avey, co-founder of web based personal genome service 23andMe in the video interview below. Linda and the other founder Anne Wojcicki just talked about the company’s ancestry, genetic comparison and similarity seeking services, the ones that will technologically turned into a social networking service later based on shared genotypes backed by the genetical connectedness of all people (in this case all 23andMe customers). I called this idea the social networking XY.0 yesterday.
Linda’s thought was the following: “If genetics has the basis to bring people together, rather than differentiate them, that’s gonna be really interesting.” (Thanks Deepak for finding the videos)
In a recent Nature report by talented journalist Erika Check Hayden called So similar, yet so different we can find the following expert opinions on the very same topic that is commercialized and envisioned now by 23andMe (citing lengthy here, emphasis by me): In his 2000 State of the Union Address, President Bill Clinton chose to emphasize something he had recently heard from a genome researcher: that humans are all, irrespective of race, 99.9% the same genetically. “Modern science,” he told his country’s legislators, “has confirmed what ancient faiths have always taught: the most important fact of life is our common humanity.” Seven years on, and four years after the final publication of the sequences from the Human Genome Project, new technologies and larger data sets are allowing genome biologists to answer a conundrum embodied in that unity-inspiring percentage: if our DNA is so similar, why do we seem different in so many ways? Read the rest of this entry »
Detailed article in the New York Times on the early experience of decoding the genetic code and interpreting the customers’ DNA via the service of 23andMe. The buzz name of the project: personalized genetics/genomics. Although other companies are mentioned briefly, the focus is clearly on 23andMe. The basics: get rid of a thousand bucks (sorry, just $999 per person) by build your order online, spit a big (2.5 mls) in a plastic tube in the postal delivered Saliva Kit, FedEx your saliva back to Mountain View (plus shipping and handling cost), wait a couple of weeks for an email and then use the company’s in-built Genome Explorer to find out the surprising details of your genetic makeup online.
From the NYT article: I soon found that I might well be sight impaired during those extra years. According to the five SNPs for macular degeneration I fed into the “Genome Explorer,” I was nearly 100 times more likely to develop the disease than someone with the most favorable A-C-G-T combination.
Biotech is the next infotech (or at least the 2 worlds need to be merged) and it is good to detect the signs of the growing biotech interest on part of the general tech crowd. At the Web 2.0 summit (organised by and for the Silicon Valley tech-media establishment) Tim O’ Reilly asked Craig Just Sequenced Venter. I suggest everyone watching the video below. It was not a terrific dialogue though as we’ve seen 2 people with a very different background talking about Venter’s discipline. I loved to hear the words ‘SNPs’ or ‘mitochondria ‘coming from Venter’s mouth in front of the biotechnologically still illiterate IT and web technology elite (my assumption, not tested statistically).
I am hanging around stem cells all the time, while there are as many interesting things happening with mitochondria too. So I asked my former supervisor, Gábor Zsurka excellent mitochondrial geneticist (especially on mitochondrial DNA recombination in human skeletal muscle) to email me his main web sources in the field in order to share. Here they are with some analysis and a nice graphics (circular human mitochondrial genome, details in the links below) from Gábor.
Gábor Zsurka, scientist and developer made another upgrade on our favorite human mitochondrial DNA visualization tool, MitoWheel: this time allele frequencies at polymorphic positions are included in the sequence bar in the form of a gray bar above or below a nucleotide representing the number of individuals carrying the SNP.
When I had worked on my MSc thesis in biology on the relation of human mitochondrial mutations and aging the paper I used most frequently was 
I am hanging around stem cells all the time, while there are as many interesting things happening with 