How DNA Works

By: Craig Freudenrich, Ph.D. & Jennifer Walker-Journey  | 

DNA Mutation, Variation and Sequencing

DNA abnormalities
Chromosome abnormalities can be inherited from a parent (such as a translocation) or be "de novo" (new to the individual). This is why, when a child is found to have an abnormality, chromosome studies are often performed on the parents. National Human Genome Research Institute

In the human genome, there are 50,000 to 100,000 genes. As DNA polymerase copies the DNA sequence, some mistakes occur. For example, one DNA base in a gene might get substituted for another. This is called a mutation (specifically a point mutation) or variation in the gene. Because the genetic code has built-in redundancies, this mistake might not have much effect on the protein made by the gene.

In some cases, the error might be in the third base of a codon and still specify the same amino acid in the protein. In other cases, it may be elsewhere in the codon and specify a different amino acid. If the changed amino acid is not in a crucial part of the protein, then there may be no adverse effect. However, if the changed amino acid is in a crucial part of the protein, then the protein may be defective and not work as well or at all; this type of change can lead to disease.


Other types of mutations in DNA can occur when small segments of DNA break off the chromosome. These segments can get placed back at another spot in the chromosome and interrupt the normal flow of information. These types of mutations (deletions, insertions, inversions) usually have severe consequences.

There is lots of extra DNA in the human genome that does not code for proteins. Scientists used to believe noncoding DNA served no real purpose. However, they have recently discovered that at least some of it is integral to the function of cells, such as determining when and where some genes are turned on or off or assisting in protein assembly. These aren't necessarily benign duties. For example, a small change in noncoding DNA that alters the pattern of a critical protein can disrupt normal development and lead to health problems.

The Human Genome Project (HGP) was initiated in the 1990s with the goal of determining the sequence of the entire human genome and to answer some basic questions: What genes were present? Where were they located? What were the sequences of the genes and the intervening DNA (noncoding DNA)? The HGP was an overwhelming success, delivering the first rough draft human genome sequence in 2000 and the final high-quality version in 2003. In the years since, it has paved the way for medical advances in everything from identifying more targeted cancer treatments to diagnosing rare genetic disease.

This task was monumental, along the order of the Apollo space program to put the first man on the moon. The HGP scientists and contractors developed new technologies to sequence DNA that were automated and less expensive.

Basically, to sequence DNA, you place all the enzymes and nucleotides (A, G, C and T) necessary to copy DNA into a test tube. A small percentage of the nucleotides have a fluorescent dye attached to them (a different color for each type). You then place the DNA that you want to sequence into the test tube and let it incubate.

During the incubation process, the sample DNA gets copied over and over again. For any given copy, the copying process stops when a fluorescent nucleotide gets placed into it. So, at the end of the incubation process, you have many fragments of the original DNA of varying sizes and ending in one of the fluorescent nucleotides.

DNA technology will continue to develop as we try to understand how the elements of the human genome work and interact with the environment.

Related Articles


  • Essays in Biochemestry.
  • "The Discovery of the Molecular Structure of DNA - the Double Helix."
  • "The Discovery of DNA Structure and Function."
  • medicine/dna_double_helix/readmore.html
  • DNA Interactive
  • "Genomics and Its Impact on Science and Society: A 2003 Primer." Human Genome Program, U.S. Department of Energy, 2003.
  • "The Science Behind The Human Genome Project." Human Genome Project Information. Aug.29, 2006. project/info.shtml
  • "The Secret of Photo 51."PBS Nova.