Sunday, November 25, 2007

This week, it's ancestry

Last weekend there was a lot of buzz about personal genomics (see Genome Technology Daily, "It was a Helluva Weekend for Personal Genomics"; or Eye on DNA, "DNA Network Members Discuss Personal Genomics Service Providers 23andMe, deCODEme, and Navigenics"; or my previous post). This weekend, it's ancestry. Today's papers had two interesting features on ancestry testing, both of which nicely echoed my own post about caution regarding ancestry testing ("On Genes"). First, the New York Times business section ("DNA Tests Find Branches but Few Roots") discusses the business of ancestry testing. The article is nice in that it compares the cost of ancestry testing by various companies, shows that results differ, and quotes Henry Louis Gates Jr. making reasoned assessments of the role that DNA testing can play. Second, the Washington Post reviews "The Genetic Strand: Exploring a Family History Through DNA" by Edward Ball("Blue Blood, Black Genes").

The theme is clear. You can only learn so much about your ancestors from DNA.

Saturday, November 17, 2007

Ready or not, personalized genetics is here.

Yesterday's announcement by deCODE genetics that they would be launching a personalized genetics service, deCODEme (news release), means that a major player in gene discovery has just joined the growing field of companies offering personalized genetic services. As I wrote in my Nature Network blog, "On Genes" in "The Scientist Blogger and the Personal Genome," information about susceptibility to disease, potential for health or accomplishment and responsiveness to therapies is found in our genes, and it is going to be made available to people who want it. A lot of people are going to want it. Most are not going to be prepared to understand it. Even Jim Watson and J. Craig Venter aren't entirely sure what to make of their genomes. Genetic counseling may morph into a profession that serves everyone, not just those who faced with clear cases of genetic disease.

Journalists and scientists also have a role to play. Let me highlight three useful responses.

The New York Times has an excellent series called "The DNA age." These articles (all by Amy Harmon, at least so far), "explore the impact of new genetic technology on American life." One published today, "My Genome, Myself: Seeking Clues in DNA" describes her use of the 23andMe service.

Bertalan Meskó, a blogger at "ScienceRoll," presents coverage of Personalized Medicine, including a summary of breaking news (today) and a review of services offered by Navigenics, 23andMe and Helix Health (last week, before the deCODE announcement).

I have started "Information on Genes," (ongenes), a web site that is intended to be a place where answers to questions on genes, genetics and genomics are provided by experts in the field. Questions will be posted anonymously but answers will not. I plan to solicit answers from people in the know. My hope is that ongenes will provide useful information to anyone trying to understand genetic tests, including professionals in the field.

Thursday, September 06, 2007

Simons Foundation funds research on sporadic autism mutations

Because I've dealt with the issue of sporadic autism linked to paternal age before (links) it seems worthwhile noting here that the Rutgers University Cell and DNA Repository will use a $7.8 million grant from the Simons Foundation to establish a new collection of DNA samples to help autism researchers study sporadic germ-line mutations. This story is covered by GenomeWeb today.

Tuesday, August 28, 2007

'On Genes," my blog on Nature Network

After commenting on Nature Network ("What's up with Nature?"), I ended up creating a new blog over there. It's "On Genes," and the URL is It's not clear what I'll put there as opposed to here. Perhaps one of the two blogs will die. Right now, the plan is to put more substantial scientific posts here and more news-oriented posts there.

Along those lines, my first real post on the Nature Network blog, "PRISM distorts our view of the open access debate" was in response to Jonathan Eisen's blog entry “PRISM – Partnership for Research Integrity in Science and Medicine – Seems like a spoof but it is real, and sad“). It makes me angry to see issues that concern me be taken up by a public relations firm that is so thoroughly dishonest. But I won't repeat that here. You can read about it there.

Sunday, July 29, 2007

Plants, Animals and the Ancient RNA Toolkit

Multicellularity has arisen independently several times, but most famously twice, in the two lineages giving rise to plants and animals. In fact, the last unicellular ancestors of these two lineages were not particularly closely related, and the last common ancestor of both plants and animals also gave rise to an enormous number of extant unicellular progeny, including all of the fungi. When I began serious work on the regulation of pre-mRNA splicing in plants in 2001 I did so with an awareness of how very similar the process is to pre-mRNA splicing in animals. This is all the more striking because so many species have lost this complexity. In fact, plants and animals share many processes that must have been present in the last common ancestor, but have been lost in many unicellular eukaryotes derived from that same ancestory. RNA figures heavily in the list, which includes microRNAs, U12 introns, the exon junction complex and complex alternative splicing.

Although the last common ancestor of plants and animals was almost certainly much more complex than most modern unicellular eukaryotes (at least in terms of its genome), it was probably not multicellular. The signals that control development in animals (wnts, hedgehog, FGFs, TGF-betas, etc.) are completely missing in plants. Likewise, the genes involved in meristem maintenance, ethylene-signaling, auxin-signaling and so on are missing in animals. It's also worth pointing out that the opisthokont clade (which includes animals and the fungi) is well-established (see the figure, which is from the Tree of Life Web Project).

Perhaps most convincing are the exceptions: the processes shared by animals and plants but missing from most unicellular eukaryotes are not missing from all. U12 introns were recently found in distantly related protists and in a fungus (see my comment). MicroRNAs were recently described in Chlamydomonas reinhardtii, a unicellular green alga (Zhao et al., 2007). There is even a miRNA family that is appears to be conserved between plants and animals and targets a homologous family of splicing regulators (Arteaga-Vazquez et al. 2006).

It is therefore frustrating to read commentaries that are written as though genomic complexity is new. For example, Ram and Ast (2007) mistakenly generalize from S. cerevisiae to S. pombe (which retains more genomic complexity of several sorts, including alternative splicing) and talk about "before and after" incorrectly. Their conclusion, that "SR proteins had already facilitated the splicing of weak introns before the evolution of alternative splicing" may be correct, but complex alternative splicing was almost certainly present in the last common ancestor of plants and animals. I say this based on the fact that it had many genes whose products function in the regulation of alternative splicing, and which have been lost in unicellular descendants lacking complex alternative splicing (among these is a repertoire of at least four SR proteins).

What is most interesting to me is the correlation between developmental complexity and retention of genomic complexity, including alternative splicing and miRNAs. It might not have evolved with multicellularity, but the ancient RNA toolkit might be very useful when it comes to building a complex organism.

Saturday, July 21, 2007

What's up with Nature? Nature network, screwy renewals, more.

Nature (Nature Publishing Group, to be precise) has been aggressively embracing the internet in new and interesting ways. Their main page at no longer has a list of journals. Instead, journals is just one of many choices (it's at the top, to be sure, and they now have no less than 77), including podcasts, gateways (which aggregate related content across journals), feeds, blogs, jobs, society partners, conferences, regional websites and miscellany (which is creatively titled "launch pad"). It's all a bit unfocused, but much of it is very useful. For example, Connotea is the shared bookmarks site that I settled on after some deliberation and experimentation, and that decision reflects the quality of the site. Nature provides useful tools oriented towards literature citations, the most important of which allow easy capture of bibliographic information (with one annoying bug that involves authors with multiple names) and export of libraries.

Nature's newest venture is "Nature Network," which is social networking for the scientist. I quickly found and joined groups for people working on bioinformatics, Drosophila and Arabidopsis. I didn't find a group working on splicing, so I created one. Nature Network could be quite useful, but I wonder if it is going to succeed. To do so, it must "catch on," a phenomenon that his hard to predict and depends very much on the site providing useful tools not available elsewhere. Right now, most of what it offers seems redundant, but at the very least it provides a professional alternative to Yahoo groups for ad hoc groups of scientists who want to create an online forum for exchange on a particular topic. One especially interesting choice is the elevation of London and Boston to a special status. I'm sure that Nature Network San Francisco will come soon, but I see lots of problems with this. Would the East Bay have their own Nature Network? I can't wait to find out if New York or Washington will be added first. Where will it end? Recalling the desperate enthusiasm with which I have often seen local politicians embrace biotechnology, I fear that this could get competitive and ugly, even before Nature Network runs out of space on their local menu toolbar.

Of course, the weekly journal is still the keystone of Nature Publishing Group. I have had a personal subscription for over 20 years and I read the journal, in print, every week, bringing it along with me to meals and whatnot. This year, they are being very aggressive about renewals and they're getting it very wrong. My annual renewal expires in September. About a month ago I received a phone call in my office, inviting me to renew. Yes, they called me. Promised a 30% discount, I did so. I renewed online in an attempt to be sure that I generated a renewal of my existing subscription, following the instructions of the person who called me. The result was an entirely new subscription, which expired not in September of 2008, but in July of 2008. I also found that I had three or four customer IDs associated with my account (for only two journals, the other being Nature Genetics). After many rounds of email with their customer service my subscriptions were simplified under a single subscriber number with the proper expiration date. I should emphasize that the replies were prompt, cordial and helpful; the problem is with their system. I assumed that everything was fine, despite the numerous entries on "/myaccount/show/subs," shown here for your amusement.

Then, I received two copies of Nature in the mail. Inquiry generated a response that came down to this:
So this is the reason you are receiving two copies of the same journal Nature but they are two different volumes and you will be receiving two copies of Nature till Sep 2007.
I decided to leave well enough alone.

Today, I received an email, from Sarah Greaves, PhD, Publisher, Nature, herself, that read in part
Your current subscription to Nature is now up for renewal. To ensure you don’t miss a single issue, I am pleased to offer you a 30% discount from our normal subscription rate.

This offer expires on SEPTEMBER 27th and is only available online through this email, so act now to ensure you don’t miss out on this exclusive rate.
I wanted to run screaming from the room, but I opted instead for writing this post.

Wednesday, February 14, 2007

Michael Crichton weighs in on patenting and the Genomic Research and Accessibility Act

In yesterday's New York Times, Michael Crichton (author of "Jurassic Park" and "Next") wrote in favor of the Genomic Research and Accessibility Act, which would ban the patenting of genes found in nature. He correctly points out that genes are not inventions and attributes the fact that they can be patented to "a mistake by an underfinanced and understaffed government agency, The United States Patent Office." I note that the bill, as described by co-sponsor Xavier Becerra, is not retroactive, so, while it's a no-brainer that the patent office should not be granting patents for the discovery of natural phenomena, this bill won't do much to facilitate the promise of personalized medicine (because most of the genes that matter have already been patented). I have discussed the possibility that we might find relief in the courts before (regarding EBay Inc. vs. MercExchange, LLC and Labcorp vs. Metabolite Laboratories). Certainly, gene patents disserve the public interest, but that is not enough, and the prospect of understanding the law in these cases is daunting.