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
       Tri-hybrid test crosses
maps three loci simultaneously
        Recombination maps are the backbone of whole-genome maps

[ 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 occurs by physical exchange of chromosomal material [IG1 14.11,13]
              Holliday Model of DNA breakage & reunion

                (An animation from Univ Wisconsin)

                   nicking of complementary strands of paired DNA  [IG1 14.15]
                         single-stranded endonucleases
                   strand displacement [IG1 14.16]
                       RecA protein causes "track jumping"
                              during  branch migration, H-bonds reform between complementary strands
                       heteroduplex formation & rotation
                            Two dsDNA molecules are covalently joined
                            Cytological chiasmata show chromosome breakage & reunion [IG1 14.12]                            
                                       [sing., chiasma: from Chi , an X shaped-letter]

                   resolution, nicking, & reunion [IG1 14.17]
                       repair (ligation) of nicks forms two recombinant DNA molecules


Recombination frequency is proportional to physical distance among loci [IG1 Res Brief 15.2, pp. 306-307]
       Unlinked loci re-assort randomly (50%)
[IG1 14.10]
       Linked loci re-assort  < or << 50%
            Crosses with cis & trans configurations yield different results
               Analysis of linked dihybrid cross: A & B loci
(PDF notes)
               Analysis of linked trihybrid cross: E F & G loci (PDF notes)
                     Determination of gene order: "switch" rule
                     Determination of recombination frequency: identify & count recombinant classes
                         1 Map unit (m.u.) = 1 centimorgan (cM) = 1% recombination
                     Correction for double-recombinant events

                     Possibility of Interference
       Genetic maps bridge classical genetics and molecular biology [IG1 15.20,21]
                Linkage maps are co-linear with chromosome
                Linkage maps for Screwworm Fly, Drosophila, and Solanum
                Linked loci separated by >50 cM show random recombination


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

     Chi-Square goodness-of-fit test
                     degrees of freedom
                     statistical significance
                     Statistical Power




Homework
: Practice trihybrid cross examples [PDF copy]


All text material 2013 by Steven M. Carr