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Selecting Mouse Strains for Genetic Diversity: Insights from Dr. James Cheverud

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12 diapositives · 255 Views · Aug 22, 2014

In this presentation by Dr. James Cheverud during the CTC Satellite Meeting of the IMGC in San Antonio on November 17, 2002, the criteria for selecting mouse strains based on maximizing genetic diversity are explored. The presentation underscores the complexity of historical relationships among mouse strains, suggesting that these relationships resemble a star rather than a branching tree. Phylogenetic analysis and multidimensional scaling techniques are utilized to model genetic diversity among strains, identified via shared microsatellite loci, providing a framework for future genetic research.

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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