New: JAX® Mouse Diversity Genotyping Array

JAX® NOTES Issue 512, Winter 2008

A new, high-density mouse genotyping microarray will be available in January, 2009. The JAX® Mouse Diversity Genotyping Array is the most advanced high-density mouse genotyping microarray available. 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 will significantly refine and increase the power of complex trait analysis by allowing researchers to identify novel variation and exclude regions that are identical by descent between parental strains.

Affymetrix Mouse Diversity Array

Raw image data obtained from a portion of the Affymetrix
Mouse Diversity Array. Oligonucleotide probes on the array
surface are bound to labeled DNA from a target sample and
laser scanned to produce this gray scale image. The image is
gridded and image analysis software quantifies the brightness
of each spot. High intensity spots, indicating high affinity
between the probe and target sequences, are used to
decode the genotypes of individual single nucleotide
polymorphisms. The entire array uses more than seven
million spots to assay 650,000 SNPs and 900,000 invariant
genomic probes.

Applications

The JAX® high-density 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 array

The SNPs for the array 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 array. 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 array 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.

Service starts early in 2009

The Jackson Laboratory is developing services for investigators interested in using the Mouse Diversity Genotyping Array. The array should be available from Affymetrix in early 2009, and services from the Laboratory should be available at about the same time. If you are interested, please register interest online.