Nucleic Acids 101
Last week’s grand
challenge:
Reading and
interpreting
genetic information
DNA Repair:
-7
DNA polymerase 10
-9
Mismatch repair 10
Genomics
Restriction
Nucleases
Ligation
Grand challenge:
Every disease requires
a tremendous amount
of interdisciplinary
effort to understand
and fight it.
Can this be streamlined?
The frequency of crossing-over is
~proportional to the physical
distance between them.
Find DNA markers close to and
flanking the gene of interest
Positional Cloning
• A chromosome has a single DNA molecule
running the length of the chromosome
• Map the gene for the trait in question in that
DNA molecule; identify close flanking
markers
• “Walk” between the flanking markers
• Identify the gene in question between the
markers
How do you map a
gene?
• Collect DNA samples from family members
in a pedigree
• Seek linkage to a polymorphic DNA marker
• Take advantage of the Human Genome
Project to identify the chromosomal region
• Narrow down the location in the
overlapping clones
What are “DNA
markers”?
• RFLP--Restriction Fragment Length
Polyhmorphism
• SNP--Single Nucleotide Polymorphisms
Mutation destroys a restriction site,
causing a RFLP
(This is also a SNP--Single Nucleotide
Polymorphism)
RFLP
STRP
or
VNTR
Pedigree of Huntington Disease
SNP’s:
Single Nucleotide
Polymorphisms
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Central Dogma