NN

NN

Mapping the Genome: A Spatial Analysis of

Gene Expression on the Mouse Chromosome

Jane Garb*

Joseph Jerry+§

Mary Hagen§

Jennifer Friderici*

Sallie Schneider§+

Karen Dunphy§

Amy Roberts§

* Baystate Health

+ Pioneer Valley Life Sciences Institute

§ University of Massachusetts

108779714

Start End

108779924 132723271 135944511 135944738

Distance (Mb) from beginning of chromosome

132748377GeneGene Gene Gene

Genes and Chromosomes Genes and Chromosomes in the GISin the GIS

The QuestionsThe Questions

How do genes respond differently in How do genes respond differently in parous and nulliparous mice?parous and nulliparous mice?

Can GIS and spatial analysis be used Can GIS and spatial analysis be used in genetic research?in genetic research?

Is there a spatial organization of Is there a spatial organization of gene expression based on biological gene expression based on biological experience ?experience ?

21, 000 genes on 21 chromosomes21, 000 genes on 21 chromosomes Starting and Ending LocationsStarting and Ending Locations Used Cartesian Coordinate SystemUsed Cartesian Coordinate System

X = starting location X = starting location Y = chromosome # (for display)Y = chromosome # (for display)

Mapped as points for analysisMapped as points for analysis

Mapping the Mouse Genome

chromosome

Mapping the Mapping the Mouse GenomeMouse Genome

chromosome

Differential Gene Expression Differential Gene Expression in the Mouse Genomein the Mouse Genome

Mb Units

The Spatial Scan StatisticThe Spatial Scan Statistic

Spatial Autocorrelation

chromosome

Clustering of Clustering of Gene ExpressionGene Expression

Mapping the gene in a GIS is now Mapping the gene in a GIS is now possiblepossible

Clustering of up-or down-regulated Clustering of up-or down-regulated genes in response to paritygenes in response to parity

Genes exhibit coordinated expression Genes exhibit coordinated expression based on their spatial locationbased on their spatial location

Mechanism for protective effect of Mechanism for protective effect of parityparity

ConclusionsConclusions

Next StepsNext Steps

What are the functions of the What are the functions of the individual genes in clusters?individual genes in clusters?

Are they related to disruption of Are they related to disruption of oncogenesis?oncogenesis?

Examine the differential response of Examine the differential response of parity to radiationparity to radiation

CollaborationCollaboration

Thank youThank you

Jane Garb*

Joseph Jerry+§

Mary Hagen§

Jennifer Friderici*

Sallie Schneider§+

Karen Dunphy§

Amy Roberts§

* Baystate Health

+ Pioneer Valley Life Sciences Institute

§ University of Massachusetts

Problems with Spatial analysis of Gene Problems with Spatial analysis of Gene Expression levelsExpression levels

relative gene location on the relative gene location on the chromosome at equally spaced chromosome at equally spaced intervalsintervals

Pre-defined region of the Pre-defined region of the chromosomechromosome

False DiscoveryFalse Discovery

Resolves Statistical Issues with Resolves Statistical Issues with Previous StudiesPrevious Studies

Analyzes actual distanceAnalyzes actual distance

Not Limited to one scaleNot Limited to one scale

Controls for multiple testsControls for multiple tests

Gene locations analyzed at actual Gene locations analyzed at actual location rather than at regularly location rather than at regularly space intervals space intervals