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Appropriate populations or families

Appropriate populations or families. a) The relatedness of the individuals to be analyzed b) How much variability (polymorphism) there is in the analyzed group of individuals c) Whether (and how) the group can be maintained for use over time and between research groups d) Size of group.

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Appropriate populations or families

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  1. Appropriate populations or families a) The relatedness of the individuals to be analyzed b) How much variability (polymorphism) there is in the analyzed group of individuals c) Whether (and how) the group can be maintained for use over time and between research groups d) Size of group

  2. a) Relatedness • Backcross, F2, Recombinant inbred lines • Humans: • Need to be able to compare maps between groups • Need suitable families for analysis - large, multigenerational

  3. The Centre d'Etude du Polymorphism Humain (CEPH)

  4. c) Maintenance

  5. d) Size

  6. The LOD Score Method

  7. What is the inheritance of the two traits? • Nail-patella syndrome - (affected individuals indicated by filled symbols) - dominant • Blood Type - A and B codominant and each dominant to O

  8. Is this cross informative? • Yes - the phase of the alleles at the two loci can be determined by examining the genotypes of the grandchildren. Note: information from the grandparents is useful in determining this.

  9. What type of cross is this? • Essentially a test cross  - AB Npnp x OO npnp (an individual heterozygous at both loci crossed to an individual homozygous at both loci)

  10. Are there any linkage associations evident? • Yes - alleles A and Np appear to be linked. Why? Because the 2 alleles are typically present in the same individuals.

  11. Are there any recombinant individuals in the pedigree? 1, noted by the asterisk in the figure. Why? He has the A blood type allele but is not affected with Nail patella.

  12. What is the percent recombination? • 1/8, or 12.5%

  13. THE LOD SCORE METHOD:

  14. Z ( ) = log [(1 -  )n-rr/ (1/2)n] Z () = (n - r) log [2 (1 -  )] + r log (2  )

  15. Z () = (n - r) log [2 (1 -  )] + r log (2  ) Z (0.1) = (8 - 1) log [2 (1 – 0.1)] + 1 log (2 * 0.1) Z (0.1) = (7) log [2 (0.9)] + (1) log (0.2) Z (0.1) = (7) log [1.8] + (1) log (0.2)

  16. Z q1 = LOD score based on q1 Z q2 = LOD score based on another recombination frequency q2 Z q3 = LOD score based on q3, etc.

  17. Calculating LOD Scores

  18. Z () = (n - r) log [2 (1 -  )] + r log (2  ) Z () = (18 - 3) log [2 (1 - )] + 3 log (2 )

  19. Genetic Distanceand Physical Distance

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