Nucleic Acids 101

Last week’s grand challenge: Reading and interpreting genetic information

DNA Repair: DNA polymerase Mismatch repair 10 -9

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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