Sean Davis, M.D., Ph.D. Genetics Branch, Center for Cancer Research National Cancer Institute National Institutes of Health Genomics for Pediatrics An Overview of Technologies for Observing the Human Genome
Simultaneous Gene Expression and Copy Number on Tiling Arrays Annotated Genes Expression Copy Number, Sample 1 Copy Number, Sample 2 Simultaneous measurement of copy number in two samples and gene expression in one sample overlayed on map of genes in the region
Simultaneous Gene Expression and Copy Number on Tiling Arrays Annotated Genes Expression Copy Number, Sample 1 Copy Number, Sample 2 Increased expression in the small amplicon does not include all genes, giving clues as to the biologically important genes in the region
Simultaneous Gene Expression and Copy Number on Tiling Arrays Annotated Genes Expression Copy Number, Sample 1 Copy Number, Sample 2 Spikes of expression at exons of ERBB2
Simultaneous Expression and Copy Number Copy Number Expression Copy Number Evolutionary Conservation Expression Copy Number Opposite Strand Expression Evolutionary Conservation Expression Copy Number
Growth in Density Over Time And these numbers are from only a single array! <ul>And these numbers are from only a single array! </ul><ul>Excel doesn't work! </ul>2,000 spots, 1997 8,000 spots, 2000 36,000 spots, 2003 85,000 to 390,000 spots, 2004 10,000,000 beads, 2005
Why did the chicken cross the road? Darwin1: It was the logical next step after coming down from the trees. Darwin2: The fittest chickens cross the road.
Sequencing <ul><li>Why use hybridization, which is just a measure of sequences, correct? </li><ul><li>Sequencing is costly, time- and labor-intensive, and inefficient </li></ul><li>Next-generation sequencing technology changes the equation such that sequencing can be more efficient, cheaper, and less time- and labor-intensive than hybridization-based methods like microarrays </li></ul>
Chromatin <ul><li>Chromatin is the complex of protein and DNA that make up the chromosomes. It is not a static structure. </li></ul><ul><li>The nucleosomes are the basic building blocks of chromatin structure. Their positioning on the genome and the regulation of their placement is not well described. </li></ul>
<ul><li>DNAse is an enzyme that cuts DNA at locations where DNA is accessible
These “accessible” regions have been associated with open chromatin
Regions of open chromatin are necessary for transcriptional and regulatory machinery to have access to gene neighborhoods and facilitate transcription </li></ul>
DNAse Hypersensitivity <ul><li>Method for finding regions of “open” chromatin
In data published with the ENCODE consortium, DNAse hypersensitive (HS) were shown to be correlated with: </li><ul><li>Histone modification
Transcription factor binding sites (experimentally determined by ChIP/chip, etc.) </li></ul></ul>Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. The ENCODE Consortium. Nature , 2007.
One day the zoo-keeper noticed that the orangutan was reading two books - the Bible and Darwin's The Origin of Species. In surprise he asked the ape, "Why are you reading both those books"? "Well," said the orangutan, "I just wanted to know if I was my brother's keeper or my keeper's brother." [email_address]
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