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Program of the 2001 International Worm Meeting - Sternberg Lab ...

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10<br />

10. A gene expression map for C.<br />

elegans<br />

Stuart K. Kim 1 , Jim Lund 1 , Stewart<br />

Scherer 2 , Moni Kiraly 1 , Kyle Duke 1 ,<br />

Min Jiang 1 , Brian N. Wylie 3 , George<br />

S. Davidson 3<br />

1 Department <strong>of</strong> Developmental Biology and<br />

GeneticsStanford University Medical<br />

SchoolStanford CA 94305<br />

2 3938 Paseo GrandeMoraga, CA 94556<br />

3 Computation, Computers and Ma<strong>the</strong>matics<br />

CenterSandia National<br />

<strong>Lab</strong>oratoriesAlbuquerque, New Mexico<br />

87185-0318<br />

The completion <strong>of</strong> <strong>the</strong> C. elegans genome<br />

sequence has identified nearly all <strong>of</strong> <strong>the</strong> genes in<br />

<strong>the</strong> genome (19,282 genes), but <strong>the</strong> function for<br />

most <strong>of</strong> <strong>the</strong>se genes remains mysterious. A scant<br />

6% <strong>of</strong> <strong>the</strong>m have been studied using classical<br />

genetic or biochemical approaches (1135<br />

genes), and only about 53% show homology to<br />

genes in o<strong>the</strong>r organisms (10,303 genes). The<br />

next challenge is to develop high-throughput,<br />

functional genomics procedures to study many<br />

genes in parallel in order to elucidate gene<br />

function on a global scale. One such approach is<br />

to use DNA microarrays to assay <strong>the</strong> relative<br />

expression <strong>of</strong> nearly every gene in <strong>the</strong> genome<br />

between two samples. Knowing when, where<br />

and under which conditions a particular gene is<br />

expressed can reveal <strong>the</strong> function <strong>of</strong> that gene.<br />

A consortium <strong>of</strong> laboratories has used C.<br />

elegans DNA microarrays to pr<strong>of</strong>ile gene<br />

expression changes in a wide variety <strong>of</strong><br />

experiments. In each experiment, RNA from<br />

one sample was used to generate Cy3-labelled<br />

cDNA, and RNA from ano<strong>the</strong>r sample was used<br />

to prepare Cy5-labelled cDNA. The two cDNA<br />

probes were simultaneously hybridized to a<br />

single DNA microarray and <strong>the</strong> ratio <strong>of</strong> <strong>the</strong> Cy3<br />

to Cy5 hybridization intensities was measured,<br />

revealing which genes were relatively enriched<br />

in ei<strong>the</strong>r RNA sample. Thirty different<br />

laboratories have collectively performed 553<br />

experiments using <strong>the</strong>se C. elegans DNA<br />

microarrays, including 179 experiments with<br />

microarrays containing 11,917 genes (63% <strong>of</strong><br />

<strong>the</strong> genome) and 370 experiments using<br />

microarrays that have 17,817 genes (94% <strong>of</strong> <strong>the</strong><br />

genome). The experiments compare RNA<br />

between mutant and wild-type strains, or<br />

between worms grown under different<br />

conditions. Many experiments have been done<br />

to date, including experiments on wild-type<br />

development, heat shock, Ras signaling, aging,<br />

<strong>the</strong> dauer stage, sex regulation and germ line<br />

gene expression. Individual microarray<br />

experiments reveal sets <strong>of</strong> genes that change in<br />

one mutant strain or growth condition. We<br />

combine <strong>the</strong> data from all <strong>of</strong> <strong>the</strong> experiments to<br />

assemble a gene expression database, and <strong>the</strong>n<br />

used this database to group toge<strong>the</strong>r<br />

co-regulated genes and visualize <strong>the</strong>m using a<br />

three dimensional expression map. By matching<br />

<strong>the</strong> expression pr<strong>of</strong>ile <strong>of</strong> an unknown gene to<br />

those <strong>of</strong> genes with known functions, <strong>the</strong><br />

expression map can be used to ascribe functions<br />

to <strong>the</strong> large fraction <strong>of</strong> genes in <strong>the</strong> genome<br />

whose functions were previously unknown.<br />

10

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