Mailund on the Internet

We just got a new paper out yesterday in BMC Medical Genetics:

Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

Schierup et al.

BMC Medical Genetics 2009, 10:20 doi:10.1186/1471-2350-10-20

Abstract

Background

A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers.

Methods

We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk.

Results

We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the Fst value) closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping.

Conclusions

The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.

Mikkel and I got involved in the project to try to use our haplotype based association mapping methods to analyse data where a single marker analysis had already shown an association with several kinds of cancer.

We didn’t really discover anything new when running our tools on the data, so to try something else we combined the case/control data with HapMap data to try to increase the number of markers through imputation.

That is when we discovered that a haplotype in the region, that is found in about 50% of Europeans (CEU and our case/control data) is only found in ~1% of Africans (YRI).  Furthermore, this haplotype was the at-risk haplotype in our case/control data and looks to be the derived haplotype when compared with the chimp genome.

Reference

Mikkel H Schierup, Thomas Mailund, Heng Li, Jun Wang, Anne Tjonneland, Ulla Vogel, Lars Bolund, Bjorn A Nexo (2009). Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups BMC Medical Genetics, 10 (1) DOI: 10.1186/1471-2350-10-20

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SNPFile – A software library and file format for large scale association mapping and population genetics studies

J. Nielsen and T. Mailund

BMC Bioinformatics 2008, 9:526; doi:10.1186/1471-2105-9-526

A fast algorithm for genome wide haplotype pattern mining

S. Besenbacher, C.N.S. Pedersen and T. Mailund

BMC Bioinformatics, 10(Suppl 1): S74 doi:10.1186/1471-2105-10-S1-S74

I just found out about Zotero when I read this blog post yesterday.

It’s a Firefox extension for managing your literature lists. I’ve been looking for a good tool for this for a bit. My trial period of Papers ran out this week, and I had pretty much decided to buy it, but it only runs on Mac and I (still) have a Linux laptop.

Now, before I decide, I’ll try out Zotero.  I will be able to use it both at work and at home (or when travelling). For Papers I’d have to buy a Mac laptop of some kind (but then, I am planning to do that anyway so it is not a major problem).

Zotero also has a nice feature (currently in beta) for synchronising literature lists. Sounds like just the thing I need.

There is plugins for Word and OpenOffice (but of course not the Word 2008 I have on my Mac), to manage references in documents. While I really prefer BibTeX, I guess this is a nice substitute when not working in LaTeX.

I don’t think Zotero exports to BibTeX, though, and that is a bit of a downer… but it is open source, so that could be fixed. There seem to be a plugin for BibTeX here, but it is marked as “invalid” whatever that means.

Anyway, I will try it out for a while, and who knows, it might be my choice instead of Papers.

If it isn’t sued out of existence, of course…

In this letter to Nature, Raghavendra Gadagkar argues that the open access model — that typically means “pay to publish, but read for free” — is doing more harm to research in the developing world than the traditional “publish for free, but pay to read” model.

The reasoning is, that having to pay to publish means that publications are not a result of the quality of ones research, but just as much a result of ones funding, and in developing countries there is less funding.

This is, of course, a valid point, but to conclude from this that the open access model — even if it means you have to pay to publish — is doing more harm than good is, well, just nuts!

First of all, many top journal charges you both for publishing and for reading the articles. With open access, at least, you can read for free.

Secondly, even if the publishing charges are much higher than the reading charge, you only pay when you have a result worth publishing. I don’t know about you, but I personally read a lot more papers than I publish, and most papers I read are never cited in my own work, because they turn out not to be relevant for my own work.

Gadagkar ends his letter with:

A ‘publish for free, read for free’ model may one day prove to be viable. Meanwhile, if I have to choose between the two evils, I prefer the ‘publish for free and pay to read’ model over the ‘pay to publish and read for free’ one. Because if I must choose between publishing or reading, I would choose to publish. Who would not?

Of course we all prefer to publish our own papers, but you cannot, and should not, publish worthwhile research if you are not familiar with the work of other researchers and have read the literature. You cannot choose publishing over reading!

I’m not saying there isn’t a problem with publication charges, but I strongly disagree with the claim that it is worse than the charge for access to papers (and I remind you, once more, that in many cases you get both of the two evils…)