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ISMB/ECCB
HL03: Eitan Rubin - Whole genome analysis of mtDNA natural evolution in human and in cancer
in advance of 1000 genomes, can we use mitochondrial dna sequencing? advantages: small size (16kb), and maternally inherited (allows human phylogeny) - Andrew Su
mitochondria have known role in cancer, but unclear if the mito genome (and mutations therein) are relevant - Andrew Su
method: compare tumor and normal mtDNA -- patient-matched. --> mutational landscape --> eliminate SNPs in normals --> find high recurrence. BUT, nothing found... - Andrew Su
method 2: from mutational landscape, look for co-mutations: two patients with multiple mutations observed - Andrew Su
one "flip-flop" observed -- mutation in tumor in one patient and in normal in another -- bi-stability? - Andrew Su
compare evolution in normal population as reference; create trees via nieghbor joining, create inner nodes, find deepest branch with mutation; conclusion: cancer uses snps that arise early in human evolution - Andrew Su
relates to african vs european haplotypes? - Andrew Su
conclusion: mtDNA is under selection in cancer; strategy of finding multiple SNPs in subset of tumors; functional prediction of 25 mtDNA snps - Andrew Su
philosophilcal question -- are tumors different species? unicellular parasites? - Andrew Su
A tumor is like a parasite branching off as a separate species from the human - Michael Kuhn
Some cancers have actually become infectious, like a separate species. Eg Tasmanian devil - Michael Kuhn