They tell me that in past years, the Biology of Genomes meeting didn't have such a focus on human genomics nor sequencing methodologies. well, this morning's session was titled "Genomics of non-human genomes"-- hence reduced to a single session, the first speaker (Barsh) had to defend the activity of doing genetics and genomics in non-human species... and I'm thinking, how crazy is that?? This IS Biology of genomes, afterall...
Anyhow, talks of note below--
Work done by Carlos Bustamante et al:
dog human and cow genomes reveal extensive human reorganization of domesticated genomes.
Prompted by large scale projects to document genome-wide variation in many species, they've taken up the CanMap (genetic diff among domestic dog breeds) and GSK Propgen projects (but he didn't talk about the GSK project).
The CanMap project is to genotype 850 dogs and 200 wolves using affymetrix v2.0 array, and use the data to understand demographic history of dogs.
Since each breed fixed for specific phenotypes in a small number of genes, this is easier to delineate than if selection occured independently. Perhaps those same genes can be implicated for the phenotypic changes we see across 'racial' or 'ethnic' lines.
They use joint association and selective sweep mapping where the unit of analysis is breed. They're looking for linked loci or alleles that are major determinants of phenotypes (for example, dog size, see Sutter et al. 2007, Science 316). They perform regression on body size, again at a breed level analysis, and model avg breed body size (using stepwise regression). They then look at predicted size against the observed, for validation and to determine outliers.
They claim that the distribution of phenotypes is not independent of the distribution of how the breeds are mapped into "genetic space" (in other words, how closely related are they). They look for PCA (but he didn't exactly describe what the high-dimensional feature vector is), assuming that the axes you come up with would relate to the phenotypic differences among the breeds.
bottom line: PCA reconstructs aspects of known breed history.
What's the punchline?
In the same way, they do a spatial prediction of ancestry... in HUMANS, and come up with a remarkable geographically associated demographic history. So we can have some insight into human demographic history migration and admixture, by looking at ourselves at the 'breed' level...
The next talk was by Andersson from Uppsala University about pigmentation mutation in horses ("grey") identified by three phenotypes (these are in fact 'white horses' in whom 'greying with age' appears at a very early age):
1. loss of hair pigmentation
2. melanoma (not because of the UV affect- their skin is actually very dark), but because of intrinsic aspects of the mutation.
3. vitiligo
4. speckling and 'blood marks' (pointing to somatic instability? <- this assumption was questioned by the audience)
They looked for the mutation responsible for this phenotype and found the locus to be a duplication in an INTRON, using hi resolution IBD mapping (a duplication that showed correlation with the phenotype). This "greying with age" is a cis-acting regulatory mutation, but its effect on expression isn't exactly clear yet.
With respect to the black spots appearing on many white horses: says that with a duplication you can recruit silencing. Others questioned whether it could be an epigenetic silencing of the alleles (without implying DNA instability).
Also of note was the grand "unveiling" of the Platypus genome sequence. This week in Nature and accompanying pubs in Genome Research.
There were many posters last night that are of direct interest to Plasmodium genomes (notably the work of Dan Jeffares, Jeff Chang, and one more). The abstracts will be available in the abstract book. There was also a talk that pertained directly to Lucia's work in building phylogenies and hypothesizing when/where lateral gene transfer occured-- although this was on Prokaryote genomes (work by Tal Dagan).
I'm checking out. Better go line up for lunch (the meeting was oversubscribed, and there are even overflow flat panel screens out on the rainy foyer, for those not fitting in the warm and musty auditorium...)
Friday, May 9, 2008
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