Mitowheel now helps you design PCR primers for mitochondrial DNA!

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.

Mitowheel upgrade: phylogenetics in motion

Gábor Zsurka has built some killer functions into Mitowheel, the human mitochondrial DNA visualization tool:

- 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

- navigation became more sophisticated

Biotechies at O’Reilly ETech, March 3 - 6, San Diego

The O’Reilly Emerging Technology Conference (ETech) is on and this year they had a growing number of biotech related sessions. Fellow SciFoo Campers like Hugh Rienhoff and Timo Hannay, Makers like Phil Torrone and Limor Fried, Brain Hackers like Ed Boyden are visiting and many more.

The second goal of 23andMe: using customer’s real health data later

Esther Dyson’s honest post on getting the genotype-health risk correlation statistics right on The Spittoon blog: What You Can Do for 23andMe (and Future Generations)

To learn more, researchers need to collect thousands of genetic profiles – and the health data connected with each of them – to find correlations between the two. That leads to a second goal of 23andMe – to collect a large database of genetic information and then come back to you over time with invitations to provide specific health data and participate in research.

We’re not asking you to do this for purely altruistic reasons - either on our part or on yours. We’re a profit-seeking company, even though our founders and employees – and directors! – all share the vision of better understanding of everyone’s genomic make-up. As for you, the research results your data help produce could translate directly into benefits for you, or at least for your children, grandchildren and friends.

Now imagine a world (2009?) in which 23andMe genotype profiles could be uploaded to your Google Health profile with one click (see picture).

Anyway, Dyson’s argument is using the “intergenerational justice” card, that is related to life extension technologies too. Dyson, an information exhibitionist also shares an interesting correspondence between her and her brother George Dyson on the growing health genomics information demand of people:

MitoWheel 1.0: the human mitochondrial genome just got visual!

Your 16569 basepair long human mitochondrial genome does a lot for you and tells a lot about you. It encodes protein subunits playing crucial role in the production and conversion of ATP, the body’s main chemical energy currency. On the other hand the actual sequence of one’s mitochondrial DNA in a particular tissue or cell population gives a lot of health associated (mitochondrial diseases, aging) and ancestry information.

So far users were restricted to non-intuitive and visually poor text based databases every time they wanted to take a look on the mitochondrial DNA. But now with MitoWheel version 1.0 (yes, it is beta) the situation is about to change. From now on you can spin MitoWheel and play MitoRoulette (details on the game later)! MitoWheel is a graphical representation of the circular human mitochondrial genome, hence the name. The sequence used is the standard Revised Cambridge Reference Sequence. The 3 main components of the app is: a search box, a sequence bar and the wheel.

MitoWheel is the brainchild of Gábor Zsurka, a human mitochondrial geneticist we’ve already met in the post on The power links of the mitochondriologist. Gábor has been doing 100% of the programming too. Disclaimer: With some suggestions and testing I qualified myself to become a member of the developer team! The wheel was made with Flash Professional 8.0 and the code harnessed the power of Actionscript , a scripting language designed specially for Flash.

What are the basic things you can do with MitoWheel, if you are a scientist in the lab or a student in the seminar or just a tech geek eager to learn biology?

- spin the wheel: browse the genome by clicking the left and right arrows in the sequence bar

- search for a nucleotide position or sequence in the search box with numbers: input: 15450 output: T

The first human genome project: mitochondrial DNA, 16.6kb, 1981, Cambridge

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?

It was once modified and corrected by Andrews et al in Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA in 1999 so today it is called the Revised Cambridge Reference Sequence and are used by mitochondriologists worldwide.

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:

23andMe on the biparental inheritance of mitochondrial DNA and more

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:

Bandelt et al., “More evidence for non-maternal inheritance of mitochondrial DNA?”
Chinnery, “The Transmission and Segregation of Mitochondrial DNA in Homo Sapiens” in Human Mitochondrial DNA and the Evolution of Homo Sapiens.

Sincerely,

The Editorial Team at 23andMe

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:

23andMe: the early bird of web based biotech startups

23andMe is a biotech focused web startup based in Mountain View, California (yes, the Googleplex neighbourhood) self-defined as “an early stage startup developing tools and producing content to help people make sense of their genetic information. Our goal is to take advantage of new genotyping technologies and help consumers explore their genetics, informed by cutting edge science. Genome deciphering technologies have reached affordable levels, allowing consumer access. For the individual, such information will provide personal insight into ancestry, genealogy and health. For society, the collection of genotypic and phenotypic information on a large scale will provide scientists with novel avenues for research.”
Briefly, they are concentrating on the enormous genomics data we already have to analyze them for customers. They are probably right, because in biotech, genomics could be the first field that has enough results, easy measurement methods (a little blood or biopsies), infotech background and enough commercial demand to make the business profitable within 1-2 years. Unfortunately, regenerative medicine and the stem cells frontier are not in this position yet. The next business step could be monetizing data from proteomics, transcriptomics. With the promising combination of computer science, biology and informatics 23andMe is an early bird of a biotech-based web domain, because there will be times when all your genes, RNAs, peptides (and in my opinion: cells and tissues) will be taken into account by your initiative to know your future prospects, and a web-based service is a proper choice for managing all of your biodata. Security problems will emerge, of course.

Human mitochondrial DNA vs. nuclear DNA

In order to introduce you the circular human mitochondrial DNA, I compare it shortly to its more famous neighbour, the chromosomal nuclear DNA. (Thx for Google Spreadsheets.)