Original Contributions

Mammalian Genome

, Volume 15, Issue 8, pp 637-647

Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis

  • Robert W. WilliamsAffiliated withPortland Alcohol Research Center, Oregon Health Sciences University
  • , Beth BennettAffiliated withInstitute for Behavioral Genetics, CB 447, University of Colorado
  • , Lu LuAffiliated withCenter of Genomics and Bioinformatics, Institute of Neuroscience, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center
  • , Jing GuAffiliated withCenter of Genomics and Bioinformatics, Institute of Neuroscience, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center
  • , John C. DeFriesAffiliated withInstitute for Behavioral Genetics, CB 447, University of ColoradoDepartment of Psychology, CB 345, University of Colorado
  • , Phyllis J. Carosone–LinkAffiliated withInstitute for Behavioral Genetics, CB 447, University of Colorado
  • , Brad A. RikkeAffiliated withInstitute for Behavioral Genetics, CB 447, University of Colorado
  • , John K. BelknapAffiliated withPortland Alcohol Research Center, Oregon Health Sciences University
  • , Thomas E. JohnsonAffiliated withInstitute for Behavioral Genetics, CB 447, University of ColoradoDepartment of Psychology, CB 345, University of Colorado

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Abstract

The set of LXS recombinant inbred (RI) strains is a new and exceptionally large mapping panel that is suitable for the analysis of complex traits with comparatively high power. This panel consists of 77 strains—more than twice the size of other RI sets— and will typically provide sufficient statistical power (β = 0.8) to map quantitative trait loci (QTLs) that account for ∼25% of genetic variance with a genomewide p < 0.05. To characterize the genetic architecture of this new set of RI strains, we genotyped 330 MIT microsatellite markers distributed on all autosomes and the X Chromosome and assembled error-checked meiotic recombination maps that have an average F2-adjusted marker spacing of ∼4 cM. The LXS panel has a genetic structure consistent with random segregation and subsequent fixation of alleles, the expected 3–4 × map expansion, a low level of nonsyntenic association among loci, and complete independence among all 77 strains. Although the parental inbred strains—Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS)—were derived originally by selection from an 8-way heterogeneous stock selected for differential sensitivity to sedative effects of ethanol, the LXS panel is also segregating for many other traits. Thus, the LXS panel provides a powerful new resource for mapping complex traits across many systems and disciplines and should prove to be of great utility in modeling the genetics of complex diseases in human populations.