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Criteria for choosing strains: Encompass Maximum Genetic Diversity Include Sequenced Strains

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

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Criteria for choosing strains: Encompass Maximum Genetic Diversity Include Sequenced Strains

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

  2. 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.

  3. Phylogeny computed by Dr. Leo Schalkwyk

  4. 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

  5. Williams Strain Set • 416 variable markers

  6. 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

  7. Measuring and Modeling Diversity • We measured genetic diversity using percent similarity among all strain pairs: • S = (# of shared microsatellite loci/total # of loci) • 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. • Contrasts between extremes along the dimensions indicate specific sets of strains that can encompass the diversity among all strains.

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

  9. First Two Dimensions of 4-Dimensional Solution. Extreme Strains on Dimension: 1: RIIIS/J <–> DBA/2J 2: KK/HIJ <– >BALB/cJ D I M 2

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

  11. Strains Chosen for CTC 8-Way Intercross • (Jim’s initial analysis, Nov 2002) • C57BL/6J (extreme on 5th 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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