August 9, 2009

How It Was Done: Mouse Diversity Genotyping Array

Methods for constructing revolutionary mouse genotyping array

In early 2009, The Jackson Laboratory began offering services using the Mouse Diversity Genotyping Array, the most advanced high-density mouse genome-wide profiling array available (JAX® NOTES 2008). The array was designed by Dr. Fernando Pardo-Manuel de Villena, University of North Carolina, and Professor Gary Churchill Ph.D., The Jackson Laboratory, both of The Center for Genome Dynamics, in cooperation with Affymetrix, and was funded by the National Institute of General Medical Sciences.

The array can simultaneously assay approximately 625,000 single nucleotide polymorphisms (SNPs) and over 900,000 invariant genomic probes (IGPs) in the mouse genome. The SNPs were carefully selected to identify highly polymorphic regions between strains and to broadly and evenly cover as much of the mouse genome as possible. The array can be used to characterize virtually any mouse in the world — existing, novel — laboratory, wild, or a complex mixture of many strains. It will be particularly useful for genotyping the Collaborative Cross and Diversity Outcross mice and for better characterizing recombinant inbred and consomic strains. This array can be used to monitor genetic quality, determine copy number variations, and study population genetics. It promises to yield many new insights into ultraconserved regions, DNA methylation, and gene-environment interactions. The Diversity Array will significantly refine and increase the power of complex trait analysis.

How was the array constructed? Finally, the word is out.

Read all about it in the Nature Methods paper (Yang et al. 2009)

Watch an interview of Professor Churchill answering the following six questions:

Watch a videoHow did you choose the array’s SNPs? (4:08)
Watch a videoHow did you ensure the array’s reliability? (2:07)
Watch a videoHow are IGPs different from SNPs, and how will they increase the array’s utility? (4:23)
Watch a videoWhat are some of the quality control measures you used to validate the array? (3:28)
Watch a videoWhat will be some to the most important uses of the array? (2:41)
Watch a videoHow will the array help researchers identify genes associated with disease? (3:35)

Learn more about the JAX® Mouse Diversity Genotyping Array Service, the Collaborative Cross and Diversity Outcross mice.  

References

(Authors in bold are Jackson Laboratory scientists.)

JAX® NOTES. 2008. New: JAX® Mouse Diversity Genotyping Array. JAX® NOTES 512:3-4.

Yang H, Ding Y, Hutchins LH, Szatkiewicz J, Bell TA, Paigen BJ, Graber JH, PardoManuel de Villena F, Churchill GA. 2009. A customized and versatile high density genotyping array for the mouse. Nat Meth Aug 9. [Epub ahead of print].