Recombination

Homologous Recombination	Non-homologous Recombination
Interaction between similar sequence	Interaction between non-similar sequence
Meiosis	Anytime
Changes haplotypes	Effects gene order (translocation)
No mutation associated	Potentially mutagenic
Mapping	-

Homologous Recombination

Genetic linkage – 2 genes on same chromosome are always inherited together

Lack of linkage – 2 genes on different chrom are inherited together 50% of the time (random) Þ independent assortment

Homologous recombination: linkage is > 50% but < 100%

Further apart 2 genes are, more likely a recombination event btwn them:

frequency of recombination is proportional to distance
can construct genetic maps based on recombination frequencies

Crossing over and recombination

Centi-Morgan (cM) = unit of distance; 1cM = % recombination per human generation » 10⁶ bp

2 genes 5cM apart are inherited together 95% (19 out of 20)
Each chromosome pair undergoes one recombination per generation in the germ line

Must be heterozygous at a loci for linkage/recombination to be detected – genetic analysis depends on polymorphic loci

Individual is heterozygous ~1/500 nt

No base pairs are gained or lost at the site of exchange

How do we make cuts at the exact same place in the 2 molecules? Þ Holliday structure formation

Surprisingly, chromosome homologs in mitotic cells can be exchanged:

very rare, but per person becomes problematic

heterozygous cell Þ homozygous daughter cells

ex: Retinoblastoma (childhood cancer)

Non-homologous Recombination

All cause rearrangement in gene order

Some random, others deliberate

Consequences: addition or removal of genetic info; disruption of existing genetic info; fusion of segments to create new genetic info

Examples:

(1) Viral integration – accident

virus lambda (l) – total specificity: DNA integrates into E. Coli chromosome with special enzymes and unique sites in both the bacterial and viral chromosomes

virus Mu and Euk retroviruses: both integrate their DNA at random; retroviruses can disrupt genes by inserting within them, can activate genes by inserting next to them, and can cause cancer

(2) Transposons – accident

discrete movable segments of DNA that insert themselves at random
can disrupt genes by inserting within them, activate genes by inserting next to them, and often carry genes for drug resistance

(3) Antibody genes – plan

rearrangement accompanying differentiation
we produce a variety of antibodies however each antibody-producing cell only produces a single type
uses a "chinese menu" system:

bring together parts of gene A, gene B, gene C by orderly recombination during differentiation

(4) Unequal crossing over

homologous recombination btwn 2 parts that are not in equivalent positions
produce deletions, inversions, duplications, amplifications and translocations (unequal)
can create new genes; can disrupt a gene