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Insights into Cell Transformation: Genes, Growth, and Disease Connections

Linda Liu used two models of cell transformation to identify 350 shared differentially expressed genes in categories of cell growth, cycle, and lipid metabolism. OLR1's role in regulation of cell growth was discovered, with implications for tumor prevention and disease severity staging. The study also highlighted links between diabetes and heart disease drugs in tumor prevention and breast cancer reduction. Genetic effects on metabolism and imprinting, alongside insights into mitochondrial defects and Y chromosome variations, were explored. The research concluded with the impact of repeat polymorphisms on global chromatin dynamics and X-linked to autosomal diversity estimation using human genomes, while mentioning the Foldit game as an innovative solution for protein folding challenges.

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Insights into Cell Transformation: Genes, Growth, and Disease Connections

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  1. Butte Lab Journal Club10/11/10 Linda Liu

  2. 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

  3. OLR1, receptor for oxidized LDL cholesterol, is needed for regulation of cell growth • Knocking it down prevents tumor formation

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

  5. 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

  6. 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

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

  8. 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

  9. 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

  10. 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

  11. 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

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