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DNA Microarrays DNA Microarrays Examining Gene Expression Examining Gene Expression

DNA Microarrays Examining Gene Expression. Prof. GrossBiology 4 DNA MicroArrays DNA MicroArrays use hybridization technology to examine gene expression

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DNA MicroarraysDNA Microarrays

Examining Gene ExpressionExamining Gene Expression

Prof. GrossBiology 4

DNA MicroArraysDNA MicroArrays

DNA MicroArrays use DNA MicroArrays use hybridizationhybridization technology to technology to examine gene expressionexamine gene expression

Attach different DNAs onto a slide as a Attach different DNAs onto a slide as a gridgrid of small of small spots, one for each gene - up to 50,000 per slidespots, one for each gene - up to 50,000 per slide

Hybridize a mixture of Hybridize a mixture of fluorescently labeled cDNAsfluorescently labeled cDNAs extracted from cells after different treatments - extracted from cells after different treatments - control control is greenis green and and experimental is redexperimental is red

ExamineExamine expression patterns by looking at levels of expression patterns by looking at levels of fluorescence for all genes in arrayfluorescence for all genes in array

Prof. GrossBiology 4

DNA MicroArray Hybridization DataDNA MicroArray Hybridization Data

increased expression

decreased expression

mRNAs at lower levels in treated cells are green, those at higher levels in treated cells are red, those that are unchanged are yellow.

each spot corresponds to a different gene

Prof. GrossBiology 4

Some Uses of DNA MicroArrays Some Uses of DNA MicroArrays

Rapid scanning of DNA or RNA populationsRapid scanning of DNA or RNA populations

Used for identifying bacterial infections in Used for identifying bacterial infections in hospitalshospitals

Used in Used in researchresearch on molecular biology of gene expression on molecular biology of gene expression Stanford MicroArray Database (Stanford MicroArray Database (SMDSMD) - gene expression ) - gene expression

information and extensive database of resultsinformation and extensive database of results

Prof. GrossBiology 4

Tumor Subgroup Tumor Subgroup ClustersClusters

Perou, et al Nature 406:747 (2000)

Prof. GrossBiology 4

Tumor ClustersTumor Clusters

basal expression Erb-B2+

normal breast-like Luminal epithelial/ER+

Perou, et al Nature 406:747 (2000)

Prof. GrossBiology 4

Tumor PortraitsTumor Portraits Breast tumors are histologically diverse and differ in their Breast tumors are histologically diverse and differ in their

responsiveness to treatmentsresponsiveness to treatments The expression profiles provided a distinctive molecular The expression profiles provided a distinctive molecular

portrait of each tumor subtypeportrait of each tumor subtype Gene expression patterns in two tumor samples from the same Gene expression patterns in two tumor samples from the same

individual were more similar to each other than either was to individual were more similar to each other than either was to any other sampleany other sample

Sets of co-expressed genes Sets of co-expressed genes (portraits)(portraits) were identified that were were identified that were correlated with specific features or physiological variationcorrelated with specific features or physiological variation

MetastasesMetastases and primary tumors had similar expression profiles and primary tumors had similar expression profiles Can lead to more effective chemotherapy decisionsCan lead to more effective chemotherapy decisions

Perou, et al Nature 406:747 (2000)

Prof. GrossBiology 4

PharmacogenomicsPharmacogenomics

examine expression profile of patientexamine expression profile of patient compare to known profilescompare to known profiles determine most effective treatment for determine most effective treatment for

this particular allelethis particular allele designing drugs for individualsdesigning drugs for individuals

Prof. GrossBiology 4

Some QuestionsSome Questions If pharmacogenomics tests are not done prior to treatment, can If pharmacogenomics tests are not done prior to treatment, can

doctor/drug company be sued?doctor/drug company be sued?

If tests are expensive, and patients pay for them, is this a kind of If tests are expensive, and patients pay for them, is this a kind of “economic” discrimination?“economic” discrimination?

If patient pays for test is she/he “hiding” information from insurance If patient pays for test is she/he “hiding” information from insurance company and subject to having policy cancelled?company and subject to having policy cancelled?

If insurance company pays for test do they have a right to the results?If insurance company pays for test do they have a right to the results?

From a business perspective, doesn’t it make sense for an insurance From a business perspective, doesn’t it make sense for an insurance company to pay for the tests since it might result in avoidance of company to pay for the tests since it might result in avoidance of cancer (a big bill!)?cancer (a big bill!)?

Discover of “accidental” information in a gene expression profile Discover of “accidental” information in a gene expression profile analysis of a patient – should the patient be told?analysis of a patient – should the patient be told?