07:50pm Thursday 12 December 2019

Jackson researchers build a better mouse (gene) trap

The JAX® Mouse Diversity Genotyping Array, designed by Jackson Laboratory Professor Gary Churchill, Ph.D., and Fernando Pardo Manuel de Villena, Ph.D., of the University of North Carolina, provides an efficient and powerful platform for characterizing mice and gaining insight into a variety of genomic inquiries.

Reporting in the journal Nature Methods, the researchers showed that the new array is the first that can simultaneously assay 123,124 single nucleotide polymorphisms (SNPs) in the mouse–a hundredfold increase over other arrays now available–and over 900,000 invariant genomic probes (IGPs) in the mouse genome. Researchers who work with mice can use it to genotype virtually any mouse. They can also better monitor genetic quality and assay gene expression and copy number variations.

In searching for the specific locations in the human genome that are associated with human diseases, scientists submit genetic samples to microarray analysis to capture the SNPs, then conduct whole-genome sampling analysis, which reduces the vast amount of data to certain selected segments. According to Churchill, the new microarray opens new possibilities for mouse genetic studies of this kind.

“You can look at new types of mouse populations, outcross populations, that have an incredibly high density of recombination,” says Churchill. “The array allows us to do fine mapping, very similar to the types of fine mapping that are going on in the human genome-wide association studies right now. The diversity outcross mice being developed at The Jackson Laboratory are an extremely useful mapping population, but they’re only useful in conjunction with a high-density genotyping array.”

Furthermore, de Villena has developed a way to use the array to detect certain epigenetic variations, which Churchill sees as one of the most exciting applications of the array going forward. Besides genetic changes such as recombination, a whole host of other mechanisms–known collectively as epigenetics–can step in during cell division and change gene function without altering the DNA sequence. Researchers are now exploring the epigenetic factors that contribute to cancer and a wide range of other diseases. One of these factors is methylation, a biological process in which a certain group of hydrocarbons replaces a hydrogen atom.

“We’re going to be able to look at many different tissues in multiple environmental conditions and ask about the epigenome,” Churchill says. “Methylation modifications are fundamental mechanisms that the genome uses to adapt to the environment on a relatively rapid time scale. I think in a matter of months we’ll be able to report hundreds of novel methylated genes.”

Dr. Churchill answers additional questions on video about the JAX® Mouse Diversity Genotyping Array

The JAX® Mouse Diversity Genotyping Array was developed in cooperation with Affymetrix, and was funded by the National Institute of General Medical Sciences. The array is now available from Affymetrix, and The Jackson Laboratory offers scientists at other institutions a genotyping service using the array.

The Jackson Laboratory is a nonprofit biomedical research institution based in Bar Harbor, Maine. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community.

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Yang et al.: A customized and versatile high-density genotyping array for the mouse. Nature Methods, published online August 9, 2009, doi:10.1038/nmeth.1359

Contact(s): Joyce Peterson, 207-288-6058


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