Chromosome Linkage, Recombination, & Mapping
In Principle:

Loci linked on the same chromosome do not assort independently
          Genetic ratios in gametes vary according to how close they are situated.

Chromosome segments are physically exchanged between chromatids during meiosis
       Chiasmata are cytological indications of cross-overs
       DNA strands are broken and undergo recombination

Recombination is proportional to distance between loci
       % recombination can be use to produce gene maps
       Trihybrid test cross maps three loci simultaneously

Results of genetic crosses can be evaluated statistically
       Ex. Chi-square test of goodness-of-fit
Loci that occur on the sex chromosomes are sex-linked
       Sex-influenced or sex-limited traits are not necessarily sex-linked:
             e.g., Breast cancer in females is associated with an autosomal locus BRCA1
                      Male pattern baldness and polycystic ovaries may be alternative phenotypes
Recombination among loci occurs two ways
       Unlinked loci on separate chromosomes assort independently,
            according to Mendel's  Rules (product rule)
       Linked loci on the same chromosome tend to assort together

Recombination of linked loci occurs by physical exchange of chromosomal material
             Holliday Model of DNA breakage & reunion
                (An animation from Univ Wisconsin)
                   nicking of complementary strands of paired DNA
                         single-stranded endonucleases
                   strand displacement
                       RecA protein causes "track jumping"
                              during  branch migration, H-bonds reform between complementary strands
                       heteroduplex formation & rotation
                            Two dsDNA molecules are covalently joined
                            Molecular "chiasmata" can be visualized by electron microscopy
                            Chiasmata show chromosome breakage & reunion                                 
                                [sing., chiasma: from Chi , an X shaped-letter]
                   resolution, nicking, & reunion
                       repair (ligation) of nicks forms two recombinant DNA molecules

Recombination frequency is proportional to physical distance among loci
       Unlinked loci re-assort randomly (50%)
       Linked loci re-assort  < or << 50%
            Crosses with cis & trans configurations yield different results
               Analysis of linked dihybrid cross: A & B loci (MGA2 6-10) (PDF notes)
               Analysis of linked trihybrid cross: E F & G loci (MGA2 6-12) (PDF notes)
                     Determination of gene order: "switch" rule
                     Determination of recombination frequency: counting recombinant classes
                         1 Map unit (m.u.) = 1 centimorgan (cM) = 1% recombination
                     Correction for double-recombinant events (MGA2 6-13, 6-14)
                     Possibility of Interference
       Genetic maps bridge classical genetics and molecular biology (MGA2 6-Found2a)
                Linkage maps for Screwworm Fly, Drosophila, and Solanum
                Llinked loci separated by >50 cM show random recombination

Results of genetic crosses can be evaluated statistically
             Ex.: Do proportions correspond to genetic predictions?

       Chi-Square goodness-of-fit test
                     degrees of freedom
                     statistical significance
             Ex.: Testing observed versus expected poportions in crosses
             Ex.: Testing occurence of interference in trihybrid cross

Homework: Practice trihybrid cross examples [PDF copy]
All text material ©2011 by Steven M. Carr