genomics

A few days ago I discussed a new paper which explores the patterns of natural selection in the genome of the X chromosome. As you know the X is "carried" disproportionately by females, as males have only one copy, so it offers up an interesting window into evolutionary dynamics (see The Red Queen for a popular treatment). Today Dienekes points me to a new paper in Genome Biology which puts the focus on the X chromosome again, Characterization of X-Linked SNP genotypic variation in globally-distributed human populations: Background The transmission pattern of the human X chromosome reduces its…

Highly Punctuated Patterns of Population Structure on the X Chromosome and Implications for African Evolutionary History: It is well known that average levels of population structure are higher on the X chromosome compared to autosomes in humans. However, there have been surprisingly few analyses on the spatial distribution of population structure along the X chromosome. With publicly available data from the HapMap Project and Perlegen Sciences, we show a strikingly punctuated pattern of X chromosome population structure. Specifically, 87% of X-linked HapMap SNPs within the top 1% of FST…

I'll return to the Research 2000 poll I discussed Wednesday, and also talk about this Gallup poll Digby discusses (and I think misinterprets), because I think we have to really think about the data we're collecting--and the questions in those polls really are different in quality from each other. But first, the 16rRNA. Something that's applicable to many fields is that you have to understand the limitations of your data, not just the strengths. In addition, you also imagine what the data would look like given certain outcomes: given scenario X, we would expect to see A, and given scenario…

As someone who is Jewish, and thus at an elevated risk for Tay-Sachs disease, a degenerative disease that inevitably kills small children, and does so miserably, I appreciate the need for genetic screening. So, while it's not perfect, I think companies like Counsyl that are selling screening for harmful genetic diseases are providing a useful service (although many conditions will still be missed). Nonetheless, their stated marketing pitch is missing something. Can you figure out what it is? From The NY Times: The company, Counsyl, is selling a test that it says can tell couples whether…

Over at The Tree of Life, Jonathan Eisen asks: What do people think are the potential benefits that could come from finishing? For those who don't know what genome finishing is, I'll let Eisen give the short summary: Finishing: Using any combination of laboratory, computational and other analyses one can both fill in gaps in the assembly and improve the quality of the assembly. This can generally be called "finishing" In the context of microbial genomes, here are some of my thoughts about finishing (italics orignal; boldface mine): Whole genomes don't come flying out of the sequencing…

David Goldstein, a geneticist at Duke, has critiqued the current focus on large-scale genomwide associations before. Now he is taking to the next step, as his group has a paper out which suggests that the reason that association studies have been relatively unfruitful in terms of bang-for-buck is due to the fact that they're picking up "synthetic associations." Rare Variants Create Synthetic Genome-Wide Associations: It has long been assumed that common genetic variants of modest effect make an important contribution to common human diseases, such as most forms of cardiovascular disease,…

Since I'm on-route to a Human Microbiome Project meeting (uncharacteristically, it's being held in a climate-friendly location--Houston; last year, it was held in Boston. In January.), reviewing this paper about the GEBA project, the Genomic Encyclopedia of Bacteria and Archaea, seemed appropriate. Sequencing bacterial genomes not only tells us a lot about the biology of the organisms sequenced, including their function, potential ecology, and evolution, but it also has a far more pragmatic use too. As we try to understand microbial communities using DNA sequencing, including those microbes…

A week ago I pointed out that in some visualizations of world wide population variation South Asians & mestizos seem to overlap which each other to a great extent. The reason for this is that both populations can be modeled as admixtures between two separate, but related, populations. Mestizos are the products of pairings between Europeans and indigenous America populations, while South Asians seem to be a stabilized hybrid population which emerged from the fusion of a West Eurasian (closely related to European) and East Eurasian (distantly related to East Asians) populations. The East…

Blaine Bettinger has an absolutely wonderful post where he compares his results for type 2 diabetes from 23andMe and DeCODEme. I really liked his post and I appreciated the way he showed the data from the two companies and elaborated on their interpretation of his genotype and his risk. Interestingly, his story goes beyond a simple relationship, where one base changes, one amino acid changes, and voila! you've got the disease. Bettinger describes what happens when there are changes in multiple genes and how those changes can have a cumulative effect on evaluating the risk of developing a…

One of the exciting things about bacterial genomics in that, within a year, we'll definitely be in the era of the $1,500 bacterial genome, although that's probably an overestimate. This cost includes everything: labor, sequencing, genome assembly, and genome annotation. While sequencing is highly automated, and has been turned into a production process, akin to a factory, high quality genome annotation, until very recently, has not. Automated software gets about 95% of gene calls right, but the other five percent differs based on the algorithm used. Unfortunately, this means that, instead…

An NSF post on Twitter this morning described an interesting study from the University of Pennsylanvia and Cornell University, that found that some people who call themselves "African Americans" may only be 1% West African, according to their DNA. The University of Pennsylvania press release contains other interesting findings as well. 365 individuals were studied and 300,000 genetic markers were examined. Some of the findings were: If you're African American, the genes most likely to have an African origin are those on your X chromosome. The article didn't mention it, but I would guess…

I've stayed away from the CRU Swifthack brouhaha, largely because the experts are far better at debunking this denialist crap than I am. But, if there were such a thing as 'genomic denialists', they would probably have a field day if they were to get their hands on what we say. For example, I'm involved in the Human Microbiome Project and we sometimes use phrases like 'bad data' or 'mediocre data.' I'm not talking about when something goes obviously wrong (i.e., controls fail), but the recognition that the technologies can fall short: technologies designed for genomics where every…

Changes in the world of personal genomics. Dan MacArthur has the details on 23andMe changing up its offerings, perhaps signalling that the money gush is long over. And deCode is finally dead. Of course, just because the .com bubble burst doesn't mean that the internet is no longer a part of our lives. New players will likely emerge in the wake of this creative destruction, and old players will adapt to survive.

Last week, I was invited to give a talk at Stony Brook University's Ecology and Evolution department about genomics (very long time readers will know that I spent four years at Stony Brook as a post-doc and research professor). The talk was well received (thank you for asking) in part, I think, because of the way I began the talk. I noted that, when I was at Stony Brook, a colleague and I spent roughly two years sequencing 10 genes from over 120 E. coli strains--and we were rightfully proud of what we had accomplished. At the time (2001-2002), this was one of the largest bacterial…

This is the story of a Turkish boy, who became the first person to have a genetic disorder diagnosed by thoroughly sequencing his genome. He is known only through his medical case notes as GIT 264-1 but for the purposes of this tale, I'm going to call Baby T. At a mere five months of age, Baby T was brought to hospital dehydrated and in poor health. In some ways, this wasn't surprising. His parents were blood relatives and they had suffered through two miscarriages and the death of one premature baby. Baby T himself was born prematurely at 30 weeks. Baby T's family history suggested that he…

If you've ever put a pair of headphones in your pocket, you'll know how difficult it is to keep a long cord in a bundle without getting it hopelessly tangled and knotted. You'll also start to appreciate the monumental challenge that our cells face when packaging our DNA. At 2 metres in length, the human genome is longer than the average human but it needs to be packaged inside the nucleus of every one of our cells, each just 6 millionths of a metre long. How does it do it? One of the secrets behind this monumental feat of folding has just been revealed by research that reveal's the human…

...the coelacanth is already being sequenced by the Broad Institute. I do like the idea of getting people excited about genomics and getting public input. Update: Don't ask me about progress; I don't know precisely. But a genome will be produced.

During one of the many framing-related flare ups (kinda like zits, aren't they?), I argued that biologists have done the following things well while confronting creationism: Calling creationists fucking morons (because they are). Arguing that a better understanding of how life evolved is good in and of itself, and can imbue us with a certain sense of wonder. Refuting specific creationist claims. But this is what I thought was missing: What we rarely do is make an affirmative, positive argument for evolution (as opposed to against creationism). I proposed one particular argument: we can't do…

Dan MacArthur did a lot of legwork in this post on Complete Genomics.

While I'm loath to disagree with ScienceBlogling Daniel MacArthur about genomics, I can't really agree with his assessment of genetic risk prediction: Wright provides a balanced review of the implications of the article, and finishes with a paragraph worth quoting verbatim: However, far from supporting calls to forbid such tests being available DTC, this highlights the need for transparencymeasurement of the DNA sequenceitself (the assay) will remain constant, the interpretation of the result (the test) is likely to change as the science develops. Amen. As I have consistently argued here on…