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Criteria for choosing strains: 1)Encompass Maximum Genetic Diversity 2)Include Sequenced Strains 3)Favor Common Strains Presentation by Dr. James Cheverud CTC Satellite Meeting of the IMGC San Antonio, November 17, 2002

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Relationships Among Mouse Strains Historical relationships among mouse strains can be quite complex, involving independent strain origins, bifurcations, and reticulation. Rather than being best represented by a branching tree, relationships may be more accurately modeled as a star, with all strains arising from a common single origin. This is similar to the relationships expected among RI strains originating from a single cross.

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Phylogeny computed by Dr. Leo Schalkwyk

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SPRET/Ei CAST/Ei SKIVE/Ei MOLF/Ei MOLG/Dn PERC/Ei PERA/Rk C58/J C57BR/cdJ C57L/J C57BL/10J RF/J C57BL/6J BTBR+Ttf/t LP/J 129T2/SvEm 129X1/SvJ 129P3/J 129S2/SvPa 129S6/SvEv KK/HIJ RIIIS/J NZW/LacJ NZB/BNJ MRL/MpJ AKR/J BUB/BnJ NOD/LtJ ST/Bj NON/LtJ SJL/J SWR/J FVB/NJ A/J BALB/cJ SM/J P/J BDP/J I/LnJ DBA/2J DBA/1J CE/J CBA/J CBA/CaJ SF/CamEi C3H/HeJ C3HeB/FeJ Phylogeny simplified by Jim Cheverud

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Williams Strain Set 416 variable markers

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SPRET/Ei CAST/Ei SKIVE/Ei MOLF/Ei MOLG/Dn PERC/Ei PERA/Rk C58/J C57BR/cdJ C57L/J C57BL/10J RF/J C57BL/6J BTBR+Ttf/t LP/J 129T2/SvEm 129X1/SvJ 129P3/J 129S2/SvPa 129S6/SvEv KK/HIJ RIIIS/J NZW/LacJ NZB/BNJ MRL/MpJ AKR/J BUB/BnJ NOD/LtJ ST/Bj NON/LtJ SJL/J SWR/J FVB/NJ A/J BALB/cJ SM/J P/J BDP/J I/LnJ DBA/2J DBA/1J CE/J CBA/J CBA/CaJ SF/CamEi C3H/HeJ C3HeB/FeJ Bold strains included in initial CTC Set (Nov 2002) Phylogeny simplified by Jim Cheverud

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1)We measured genetic diversity using percent similarity among all strain pairs: S = (# of shared microsatellite loci/total # of loci) 2)We used Non-Metric Multidimensional Scaling to order the strains in a 4- Dimensional Space. This procedure minimizes the squared deviation of the predicted 4D distances from the observations. 3)Contrasts between extremes along the dimensions indicate specific sets of strains that can encompass the diversity among all strains. Measuring and Modeling Diversity

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Multidimensional Scaling Results Dim.Stress% Variance 3D 0.17 79 4D 0.13 84 5D 0.10 87

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First Two Dimensions of 4-Dimensional Solution. Extreme Strains on Dimension: 1: RIIIS/J DBA/2J 2: KK/HIJ BALB/cJ DIM2DIM2

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Last Two Dimensions of 4-Dimensional Solution. Extreme Strains on Dimension: 3: AKR/J – SM/J 4: 129x1/SvJ – RIIIS/J DIM4DIM4

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3D DistanceDistance

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5D DistanceDistance

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4D DistanceDistance

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Strains Chosen for CTC 8-Way Intercross (Jim’s initial analysis, Nov 2002) C57BL/6J (extreme on 5 th Dimension) RIIIS/J DBA/2J BALB/cJ SM/J 129X1/SvJ AKR/J KK/HIJ This set maintains about 90% of the variation in the 4-Dimensional solution and thus about 75% of the genetic diversity of standard mouse strains

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As with averages, researchers need to transform data into a form conducive to interpretation, comparisons, and statistical analysis measures of dispersion.

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