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A novel approach to genetically dissect complex quantitative traits using a diallel cross of recombinant inbred strains. Alexander V. Osadchuk 1 , David C. Airey 2 , Lu Lu 3 , David W. Threadgill 4 , Robert W. Williams 3. 1 Institute of Cytology and Genetics, Novosibirsk, Russia
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A novel approach to genetically dissect complex quantitative traits using a diallel cross of recombinant inbred strains Alexander V. Osadchuk1, David C. Airey2, Lu Lu3, David W. Threadgill4, Robert W. Williams3 1Institute of Cytology and Genetics, Novosibirsk, Russia 2Vanderbilt University, Department of Pharmacology, Nashville, TN 3Center for Neuroscience and Department of Anatomy and Neurobiology, University of Tennessee, Memphis, TN 4Dept of Genetics, University of North Carolina at Chapel Hill The 3rd Annual Meeting of the Complex Trait Consortium, Oxford, UK, 1-3 July, 2003
Extended RIX design of the CXB set (78 nonreciprocal F1 crosses, 13 RI strains and 2 progenitor strains and their F1 hybrid) The data consist of 1338 mice, 685 males and 653 females, ~ 12 mice per isogenic cross. The 3rd Annual Meeting of the Complex Trait Consortium, Oxford, UK, 1-3 July, 2003
Genotype distribution for 1-locus inheritance in the extended RIX design of the CXB set (78 nonreciprocal F1 crosses, 13 RI strains and 2 progenitor strains and their F1 hybrid) Alleles designated as "0" or "1" are inherited from BALB/cByJ or C57BL/6ByJ progenitor strains, respectively
L1 L3 L2 L4 4-Locus least squares linear segregation model for RIX cross
Two-step procedure for searching adequate solutions PC program for obtaining initial (“bootstrap”) solution The program is able to perform an exhaustive search of up to 230 different genotype variants of RI strains PC program for search all adequate solutions around the initial or selected solution (about 20 000 different genotype variants is examined under each iteration)
The Best Solution for 1-Locus Segregation Model of Cerebellum Weight in 91 Isogenic Lines The 3rd Annual Meeting of the Complex Trait Consortium, Oxford, UK, 1-3 July, 2003
The Best Solution for 2-Locus Segregation Model of Cerebellum Weight in 91 Isogenic Lines The 3rd Annual Meeting of the Complex Trait Consortium, Oxford, UK, 1-3 July, 2003
4-Locus Segregation Model of Cerebellum Weight Adjusted for Age and Sex in 94 Isogenic Lines L1 L3 L2 L4
All 14 adequate (p<0.001) solutions based on analysis among 94 isogenic lines variation and F2 generation of progenitor strains (SDP is indicated for each locus) The 3rd Annual Meeting of the Complex Trait Consortium, Oxford, UK, 1-3 July, 2003
L1 L3 L2 L4 The Champion Solution for 4-Locus Segregation Model of Cerebellum Weight in 94 Isogenic Lines ANOVA
Predicted (81) and Observed (53) Genotypic values for Cerebellum Weight Males Females
Histogram of the Cerebellum Weight in F2 Generation of Progenitor Strains
SDP Variation among 14 Adequate solutions for 4-Locus Segregation Model of Cerebellum Weight in 94 Isogenic lines Unambiguously inherited, statistically significant and insignificant inherited alleles are marked by light turquoise, turquoise and grey colors, respectively.
Mapping of Model Loci on 801 Microsatellite Marker Map in 13 RI Strains of CXB Set
Perfect RIX design Treadgill’s RIX design Completed RIX design Experimental Designs using a diallel cross of RI Strains