The International Complex Trait Consortium

Genome instability in mice and 20-way cross

Weikuan Gu

University of Tennessee Health Science Center, Center of Genomics and Bioinformatics, Memphis, TN 38163 USA

ABSTRACT
 
As our research focuses switch on to the complex traits, we realize that the mouse genome is not complicated enough to represent the complexity of human populations. The effort to create a mouse with a genetic structure that is more like a human, therefore, is under its way. One such a favorite strategy currently under discussion is to make a 20-way cross to create approximately 500,000 recombinant inbred strains (RIXs). This is an excellent project but it requires efforts from many scientific fields and faces many challenges. Tracking down the breaking points in RIXs with molecular markers is one of many challenges.

In order to accurately detect the recombinant point, not only a large number of molecular markers but also the representativity and instability of the molecular markers have to be considered. In this regard, we will need answers to some of the questions. 1) Does the same genotype of a microsatellite marker really represent the same genome among mouse strains. 2) How well the SNP represent the genome? 3) How microsatellite markers mutate in the mouse genome (e.g. different types of microsatellite markers in different strains, di, tri, and tetra microsatellites and the number of the repeats, the mutation rate in different genome region/chromosome)? 4) The SNP is relatively more stable than microsatellite markers. However, with large crosses and number of genome, mutations in SNP will be another problem in our 500,000 RIXs. 5) Spontaneous mutations will be an additional consideration in our effort of 500,000 RIXs.

Recent completion of human and mouse genome sequences by public and private sectors along with other new technologies for polymorphic analysis allow us to detect and screen large numbers of molecular markers along mouse chromosomes. Therefore, carefully selecting a set/s of suitable molecular markers are necessary for the 20-way cross. In addition, it may be necessary, in parallel to the breeding program, to conduct an analysis of genome instability and genome comparison among strains used in the breeding program. Such a project will enable an accurate screening of the recombinant points in the RIXs. Detailed information will be presented and discussed.

References

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Huang QY, Xu FH, Shen H, Deng HY, Liu YJ, Liu YZ, Li JL, Recker RR, Deng HW. (2002) Mutation patterns at dinucleotide microsatellite loci in humans. Am J Hum Genet. 70(3):625-34