At its heart, this paper is a challenge to a common assumption used in statistic genetics: the assumption of additive genetic risk. This states that genetic risk factors act independently of each other, with each variant increasing genetic risk by the same amount regardless of what other risk factors are present*. Of course, this is clearly a spherical cow situation, we know that the cell is full of complex interactions of various sorts, and a mutation cannot help but be effected in some way by the rest of the genome. But mathematically the assumption simplifies much of the complexity of statistical genetics, and allows you to do a number of things that would be very hard otherwise. We generally think additivity is a good approximation; it doesn’t matter if it is slightly wrong, and we’d have picked up if it were very wrong.

Zuk et al’s claim is that it is possible that additivity is wrong, that did not pick it up, and that it really does matter. This blog post will discuss the specific arguments that Zuk et al make against additivity. Some of the broader implications of the research is discussed over at Genomes Unzipped, and in particular looking at what this does and doesn’t say about total (not additive) heritability.

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A new group blog, res gerendae, came online at the end of last year, and is interesting for a few reasons. Firstly, it is written by Classics students (those who study Roman, Greek and other societies of the Classical antiquity), who aren’t really known for their blogging. Secondly, the blog is open to all the Classics grads of Cambridge University, potentially acting as a voice for all students of the Faculty of Classics.

So far you can read about graffiti then and now, the real location of Troy and a surprisingly technical reading of a postcard.

Lets hope other student bodies take inspiration from this, and do their bit to get students involve in writing about their field.

For me, the hightlight of yesterday was (somewhat obviously) the Individual Resequencing for Complex Trait Genetics session. This was organised by Mark Daly and Ben Neale of Mass. Gens. Analytic and Translational Genetics Unit, and gathered together a number of the Big Men (all men, unfortunately) of disease association together to talk about the many and varied Next-Generation sequencing studies they have been working on. I’ve summarised some of what was said below.

As always, you can find more coverage of ICHG on twitter (@lukejostins for me, #ICHG2011 for aggregated coverage).

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The debate was pretty lively, and in parts both enlivening and depressing. Below are a few points that I found interesting.

As always, you can find more coverage of ICHG on twitter (@lukejostins for me, #ICHG2011 for aggregated coverage).

Different perspectives

Joris Veltman described his exome sequencing of 500 individuals with intractable disease, and noted that there has been much success, and very little evidence of harm. Ségolène Aymé mentioned NIH targts that hope to see almost all genetic diseases diagnosed by 2020, and new treatments for rare diseases to be developed simultaneously. There seemed to be a solid consensus across the panel that sequencing should be rolled out as a standard tool in the diagnosis of genetic diseases, provided that the approach is a targeted one, restricted to finding the pathogenic mutation(s) causing the disease.

More controversial was the role of sequencing of healthy individuals, and the general return of data to patients or doctors for any reason other than directly diagnosing a genetic disease. Rade Drmanac, chief scientific officer of Complete Genomics, was obviously strongly in favour of everyone having their genome sequenced, and made it clear that Complete Genomics intends to start offering sequencing to doctors in the future. In his vision, genomes are sequenced at birth, and an initial analysis of immediately actionable results (e.g. potential genetic diseases) is passed to the doctor and patient, with further analyses being carried out if and when they are required.

Michael Hayden immediately dismissed this as hype. He pointed out how unable the US is to handle medical sequencing, with no good systems of reimbursement, a massive shortage of genetic councilors, and a general lack of training in the medical profession.While more positive in general, Louanne Hudgins also expressed worries about the lack of knowledge of genetics among doctors, with some truly scary examples of MDs failing to understanding even the most basic genetics.

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As always, I aim to report on this blog at least one thing that I found interesting for every day of the conference. Also as always, I will be tweeting the odd thing of interest from my twitter feed @lukejostins, and you can get more in-depth coverage on the hashtag #ICHG2011.

This year I am also giving a talk. In fact I am giving one of the closing talks of the conference! (to put an overly positive spin on the graveyard slot). I’ll be talking at 3.15pm on Saturday in the Statistical Genetics IV session (room 517BC), so if anyone is interested in seeing a little something on disease risk prediction in families, come along!

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The quality of all the talks remains very high, but today I am only going to write about two. What I liked about both of these talks was the link between recent human evolution, geography and phenotype-associated traits, despite being two very different methodologies.

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As a slightly different approach to the last two days, all the talks I am going to report on today are based on one concept. Suppose you have sequenced a new genome, and you want to get the best out of it. Maybe you want to find a Mendelian mutation or a large-effect risk factor, or just look at personal genome for overall assessment. Today’s Computational Genomics session was full of great ideas for what you can do to get the most out of your shiny new genome sequence.
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Ewan Birney presented a deluge of information on ENCODE data with a host of interesting insights that I was entirely too jetlagged to take in at all, so will not attempt to discuss. However, there were a few interesting talks that I think I followed well enough to communicate.

As usual, you can follow live tweets from the conference at #bg2011. While poor WiFi performance has lead to somewhat patchy coverage of talks, most presentations have at least one person reporting on them.

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The subject of the evening session was high- throughput genomics. There were a lot of cool talks, but two in particular got my excited, for reasons that I will explain at the end of the post. Both describe very elegant new sequencing-based techniques for studying gene regulation through transcription factor binding.

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The Biology of Genomes meeting can be somewhat difficult to navigate for a blogger and tweeter. There has been some controversy about the extent to which scientists can write about the conference via social media platforms, and I have no interest in pissing people off, so we will have to see what I can and cannot write about. I hope to put together posts about talks where the speakers specifically allow blogging coverage.

One thing I can write about is the laboritory itself. Me and Daniel are staying in a bizarrely picturesque little wood cabin in the woods on the Cold Spring Harbour Lab site:

CSHL is full of interesting wildlife, such like geese and swans, along with squirrels and a host of birds. As a European, one of the most exciting aspects is the presence of Eastern Chipmunks, which hang around in the woods around the cabins, looking cute but very slightly like they are planning something:

The contrast between my experiences this year and last is stark. This year, I have already had a good flight, a pretty wood cabin and an unexpected wine and cheese party and poster session with a group of honeybee scientists. Last year, I had an airway full of ash clouds, a dingy motel on a busy road, and a rickey old school bus with dodgy seatbelts and a tendency to violently launch you into the air at every bump. So all bodes well so far.

The cabi image is actually from Hugh Robertson’s website, and the chipmunk is from Wikipedia.