Butte Lab Journal Club10/11/10

Linda Liu

- Used 2 models of cell transformation- Mammary cells - Fibroblasts transformed with Ras

- Identified 350 shared differentially expressed genes in 3 categories- Cell growth- Cell cycle- Lipid metabolism & metabolic/cardiovascular disease

- OLR1, receptor for oxidized LDL cholesterol, is needed for regulation of cell growth

- Knocking it down prevents tumor formation

- Separating cancers into stages reveals higher expression of OLR1 in more severe disease

- Showed that drugs used to treat diabetes and heart disease also prevented tumor formation

- Diabetes drug metformin decreases breast cancer incidence, which was confirmed in an independent study

- Found that 1300 loci had spatial- and temporal-specific effects depending on which parent the allele came from- Many of the genes are expressed in brain & are involved in feeding and metabolism, consistent with theories of sexual selection on imprinted genes

- Black line = parental expression bias identified by RNA-seq- Assessed imprinting by chi-square test

- complex I of mitochondrial respiratory chain is encoded by both nuclear & mtDNA- defects in complex I hard to diagnose, could be in any of 25 previously identified genes, or novel mutations

- Y chromosomes in Drosophila have varying repeat sequences, which is known to contribute to differences in Y chromosome heterochromatin. - These heterochromatin differences have previously been shown to contribute to Y-linked regulatory variation (YRV) of gene expression. - This paper suggests that a repeat polymorphism on Y affects global chromatin dynamics

- Used 6 human genomes to estimate X-linked to autosomal diversity- Expected value: 0.75- Deviated from this

- Direction of deviation depended on how far a sequence is from nearest gene

- Foldit game – multiplayer online game to get users to help solve computationally intractable problems like protein folding- In many cases, players’ problem-solving and visual skills outperform a computer program- Can use the most common approaches used by humans to inform new computational algorithms

- Ingmar Riedel-Kruse at Stanford is doing similar work