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Genome Annotation by Mutation

a living organism. It is made of deoxyribonucleic acid, or DNA, a twisting, double ladder-shaped molecule made from numerous base pairs of four building blocks: nucleic acids designated A, C, G and T.

DNA in each human cell has about 3 billion base pairs, arranged into 23 pairs of chromosomes. Those chromosomes include roughly 20,000 genes, which carry the code needed for cells to produce the proteins used to make body parts and carry out most functions in living organisms. Genes typically have 50,000 base pairs but can range in size from a few thousand to 300,000 base pairs, Capecchi says.

The genes include only about 2.5 percent to 3 percent of human DNA. In between the genes are vast stretches of non-coding or non-gene DNA.Some pieces of non-gene DNA are regulatory sequences that turn genes on or off, or turn their activity up or down like a dimmer switch. Other DNA sequences are responsible for folding and packing DNA into the nucleus of each cell.

Five percent to 50 percent of DNA is considered useless junk, depending on who you ask, although probably at least half of the junk DNA is going to end up having a pretty important function, Capecchi says.

Capecchi is known for developing gene targeting, in which mice are bred with a gene disabled or knocked out to see what goes wrong, thus revealing the genes normal function and how disease makes it malfunction. But DNA regulatory sequences between genes also can mutate to cause disease by making the genes they control malfunction.

We know how to knock out genes, and that technology is very good at changing any given gene in a designed manner, Capecchi says. The negative side is, it takes work and money to do that. The new method is a cheaper way of knocking out a gene as well as regulatory sequences.

The new method is a faster, cheaper way of mutating DNA, costing $200 to create each mouse with a mutant gene or other DNA sequence, although
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