The Mouse Diversity Genotyping Array: an advanced, high-density mouse genotyping microarray

The Mouse Diversity Genotyping Array is an advanced high-density mouse genotyping microarray. It was designed with National Institute of General Medical Sciences (NIGMS) funding by Dr. Fernando Pardo-Manuel de Villena, University of North Carolina, and Professor Gary Churchill, The Jackson Laboratory Center for Genome Dynamics. The 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 array is a powerful tool for understanding genetic and copy number variation between mouse strains or among offspring from a genetic cross. Capable of ascertaining variation across diverse Mus musculus subspecies, it significantly refines and increases the power of complex-trait analysis by allowing researchers to identify novel variation and exclude regions that are identical by descent between parental strains.

Applications

The Mouse Diversity Genotyping Array can be used in numerous applications, including the following:

• Characterizing novel or existing mouse strains or lines— for example, in association or QTL studies
• Monitoring strain genetic quality
• Characterizing or comparing any set of mouse DNA samples (e.g., from tumor tissues or cell lines) — for applications such as array comparative genomic hybridization
• Assaying copy number variations (CNVs) (by using IGPs)

Construction of the microarray

The SNPs for the microarray were carefully selected from publicly available SNPs known to be highly polymorphic among characterized strains. Strain distribution patterns for SNPs in overlapping 100kb windows across the genome were compiled, and representative SNPs for each pattern were put on the microarray. There is approximately one SNP for every 4.3kb across the genome. IGPs were computationally mined from the NCBI Build 36 genome assembly of JAX^® Mice strain C57BL/6J and genomic sequence data from M. m. molossinus (MSM/Ms), an inbred strain derived from the Japanese wild mouse. Of all exons annotated by Ensembl (version 46) in the C57BL/6J genome assembly, 93% have at least one IGP. Of the 481 mouse/human/rat ultra-conserved genomic regions in the C57BL/6J genome assembly, 238 have at least one IGP. Whereas all SNPs on the microarray have been validated with a prototype array, the IGPs have not. All SNPs and IGPs are annotated by position in the NCBI Build 36 genome assembly. All SNPs are also annotated by reference SNP cluster (rs) identifiers from dbSNP at the NCBI.

Investigators interested in using or learning more about the Mouse Diversity Genotyping Array should contact Affymetrix.