RECOMBINATION AND LINKAGE D 1 Chromosomes D 2 DNA D 3 Diploid vs Double Stranded D 4 by malj

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									RECOMBINATION AND
     LINKAGE




                    D-1
Chromosomes




              D-2
DNA




      D-3
  Diploid

     vs.

Double Stranded


                  D-4
               Genetic markers
    Sections of DNA that generally satisfy the
     following:

    A. We know where they are in the genome.
    B. We have the ability to examine (genotype) them.
    C. Different variants (alleles) exist in the
       population.



                                                         D-5
                   SNPs
 Single Nucleotide Polymorphisms
 Markers
 Variation between individuals (alleles)
  involve a single base change.
 Typically only two alleles (though up to
  four alleles possible).



                                             D-6
     SNP Variation



AT                   CG




                          D-7
                  Alleles:

     AT            A&T             TA



     GC            A&G              AT



Haplotype: A-G                Haplotype: T-A
                 Genotypes:
                  A/T, A/G                D-8
                       Allele
  A particular variant of DNA at a specific location


                    Genotype
 One allele from each parent; this combination forms
  a genotype at a given genomic position: A/C


                    Haplotype
  Alleles received together from one parent

                                                        D-9
Recombination




                D-10
Linkage




          D-11
Recombination Fraction




                         D-12
Map Distance




               D-13
Choice of Map Function




                         D-14
Choice of Map Function




                         D-15
Physical Distance




                    D-16
Map Construction




                   D-17
Maximum Likelihood




                     D-18
Backcross Data




                 D-19
Backcross Data




                 D-20
Backcross Data




                 D-21
Backcross Data




                 D-22
             Map Construction

• All marker ordering methods suffer from the problem
  that we can’t evaluate every possible marker
  ordering.

• Methods have been developed to search the space
  of possible orderings in such a way as to identify a
  good (e.g. highly likely) ordering without examining all
  possible orderings.

   – Example: simulated annealing

                                                       D-23
Map Construction Conclusion




                              D-24
Map Construction




                   D-25
Linkage Analysis




                   D-26
Linkage Analysis




                   D-27
Types of Linkage Analysis




                            D-28
Parametric Linkage Analysis




                              D-29
Phase Unknown: Complete
       Penetrance




                          D-30
Phase Unknown: Complete
       Penetrance




                          D-31
Phase Unknown: Complete
       Penetrance




                          D-32
Phase Unknown: Complete
       Penetrance




                          D-33
Phase Unknown: Complete
       Penetrance




                          D-34
Phase Unknown: Complete
       Penetrance




                          D-35
Phase Unknown: Complete
       Penetrance




                          D-36
Phase Unknown: Complete
       Penetrance




                          D-37
Lod Scores




             D-38
Example 2: Fully penetrant, phase
          ambiguous




                                D-39
Example 2




            D-40
Example 2




            D-41
Example 3: Fully penetrant, general
            pedigree




                                 D-42
Example 4: Reduced Penetrance,
      general pedigree




                                 D-43
Reduced penetrance: general
         pedigree




                              D-44
Multipoint linkage analysis




                              D-45
Location Score Profile




                         D-46
Multipoint Analysis




                      D-47
Nonparametric Linkage Analysis




                            D-48
Allele Sharing (Sib Pairs)




                             D-49
Allele Sharing sib pairs




                           D-50
One Particular Method




                        D-51
One Particular Method




                        D-52
One Particular Method




                        D-53
Spairs: IBD approach




                       D-54
Spairs Example




                 D-55
Spairs Example




                 D-56

								
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