Microarray Design & Analysis

What is Microarray Analysis?

Microarray analysis is the characterization of DNA or RNA from a sample of interest. Using microarrays it is possible to measure the biological signature of a sample, for example, to determine if mutations have occurred or which genes are expressed.

Developing New Microarray Technology

As part of the Center for Genome Dynamics and in collaboration with Dr. Fernando Pardo-Manuel de Villena at the University of North Carolina at Chapel Hill, we have designed a new microarray, the Mouse Diversity Genotyping Array. The array is the most advanced high-density mouse genotyping microarray currently available. This single, custom Affymetrix array can simultaneously assay over 600,000 single nucleotide polymorphisms (SNPs) and over 900,000 invariant genomic probes (IGPs) in a mouse DNA sample. The Jackson Laboratory now offers a new Mouse Diversity Genotyping Array Service utilizing this innovative genotyping microarray.

Improving Microarray Performance and Evaluation

Although microarray technology is extensively used in biomedical research, further development is needed of the statistical and computational tools for both the experimental design and interpretation of data resulting from the application of this technology. The Churchill Group strives to improve the way microarray experiments are designed and analyzed. We have demonstrated that thoughtful experimental design is critical, for example, the importance of randomization in obtaining reproducable results. Recognizing that a range of technologies is available to investigators, we have performed cross platform comparisons to determine the consequences of using different microarrays. Our group has also developed novel analysis methods, for example, for three- and four-color microarray systems, and small microarray experiments.

Characterizing the Diversity of the Mouse Genome

The completion of the design and production of the Mouse Diversity Genotyping Array, a customized and versatile high-density genotyping array for the mouse, represents a starting point for new directions of inquiry. The array design is based on our analysis of the phylogenetic structure of laboratory mouse populations and it captures the full range of genetic diversity in classical, wild-derived inbred and wild-caught mouse populations. As part of the Center for Genome Dynamics and in collaboration with Dr. Fernando Pardo-Manuel de Villena, we are performing exhaustive genotyping of existing mouse strains which will form the basis of a complete characterization of the laboratory mouse genome. We are also exploring novel applications of the array, beyond standard SNP genotyping, including copy number variation, allele specific gene expression and differential methylation analysis.

Understanding the Relationship Between Gene Expression and Disease

We perform microarray experiments to investigate a wide range of traits including bone differentiation and mass, body composition, digestion, kidney disease, breast cancer and sleep. These studies provide evidence to support specific candidate genes and reveal the network of gene-gene and/or gene-environment interactions underlying these traits.

Facilitating Access to Microarray Data via Web-based Interfaces

We are currently developing online tools which would enable researchers to more easily query and visualize their microarray data following statistical analysis.

Resources

Microarry Design & Analysis

Education

Short Course on Systems Genetics

Software

R/maanova
J/maanova

Analytical Tools

Mouse Diversity Genotyping Array

Datasets

Gene Expression

Example Publications

Randomization in laboratory procedure is key to obtaining reproducible microarray results
Yang H, Harrington CA, Vartanian K, Coldren CD, Hall R, Churchill GA.
PLoS ONE. 2008;3(11):e3724.
[ Full Text ]

PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells
Shockley KR, Lazarenko OP, Czernik PJ, Rosen CJ, Churchill GA, Lecka-Czernik B.
J Cell Biochem. 2009 Feb 1;106(2):232-46.
[ Full Text ] [ datasets ]

Fundamentals of experimental design for cDNA microarrays
Churchill GA.
Nat Genet. 2002 Dec;32 Suppl:490-5.