Nucleic Acids 101

Last week’s grand challenge:

Reading and interpreting

genetic information

DNA Repair:DNA polymerase 10-7

Mismatch repair 10-9

Genomics

RestrictionNucleases

Ligation

Grand challenge:Every disease requiresa tremendous amount

of interdisciplinaryeffort 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 orVNTR

Pedigree of Huntington Disease

SNP’s:Single Nucleotide Polymorphisms

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