Saturday, April 12, 2008

Mapingp cellular susceptibility to HIV

A really neat paper (Loeuillet et al.) in PLoS Biology identifying a candidate SNP for cellular susceptibility to the HIV-1 virus. The paper adding to our growing knowledge of the genetics of HIV susceptibility (see a review of the paper by David Goldstein).

Rather than investigating this in patients with the disease, the paper initially measures how susceptible different cell lines are to HIV. The paper uses the CEPH cell lines (immortalized lymphoblastoid B cells) to do an initial linkage map, and identified a broad candidate region. They followed this up using the CEU HapMap cell lines to confirm and fine map the variant. The authors then confirmed the SNP association was also present using the more biologically relevant CD4+ T-cells. Finally on the association front they showed that the SNP is associated with disease progression in patients.

The use of the HapMap and CEPH cell lines to map variants affecting cellular phenotypes is a really interesting approach. One which I'm sure we will see a lot more of in the future. At least some cellular phenotypes are likely to be easier to map as they likely have a simpler basis than complex diseases. I'm slightly surprised that the authors did not do a genome-wide association study of this cellular trait (after all they are HapMap cell lines) and instead restricted themselves to doing an association study in the region of significant linkage. Obviously a GWAS would have to meet genome-wide significance, but the region of significant linkage could have been up-weighted or considered separately in this analysis.



Hat tip to Tree of Life.

Reference:
Loeuillet C, Deutsch S, Ciuffi A, Robyr D, Taffé P, Muñoz M, Beckmann JS, Antonarakis SE, Telenti A.
In vitro whole-genome analysis identifies a susceptibility locus for HIV-1.PLoS Biol. 2008 Feb;6(2):e32
Goldstein DB.
Genomics and biology come together to fight HIV
PLoS Biol. 2008 Mar 25;6(3):e76

6 comments:

Daniel said...

It certainly is a neat paper (I blogged on it myself a while back). I'm sure they considered doing a GWAS, but with only 56 assayed HapMap samples their power would have been way too low.

G said...

I'd spotted it from the GoldStein review, so not realised that the paper was actually a few months old.

G said...

btw I agree with your power comment. I guess I would just like to know that there isn't anything genome-wide significant out there.

Daniel said...

There's been a previous GWAS for variation in viral load in 486 HIV patients. Seems to have got pretty good results for the sample size - three SNPs explaining about 14% of the total variance. All of them are on chromosome 6, in and around the HLA cluster. None of the previously known variants (e.g. CCR5) reach genome-wide significance.

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