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  • Educator Mark J. Kiel
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THE BIOLOGY OF DNA: DNA is truly a fascinating molecule. It is amazing to think that 4 little letters could account for not only all of human diversity but all of the differences between every form of life on Earth - from bacteria to butterflies to blobfish! To learn more about how DNA works and what it does, check out the following websites: http://www.dnalc.org/websites/ and http://www.dnaftb.org/THE HUMAN GENOME PROJECT: The sequencing of the first human genome was a watershed moment in science. Although there was some initial debate, the Human Genome Project has contributed immeasurably to our basic understanding of human biology and disease. To learn more about how it was done and by whom, check out the following websites: http://www.genome.gov/10001772 and http://www.genome.gov/25019879 ALTERNATIVE TECHNOLOGIES: Using colored letters to sequence the genome is one of the most common methods but there are several others. Some of these methods of detection are so sensitive that they can detect the light given off by a single letter in real-time as enzymes add letters to a growing DNA strand. Other methods to amplify the signal given off by each letter exploit the fact that the enzyme produces an H+ atom as it makes DNA. If current from this H+ atom is detected by a tiny semi-conductor underneath growing DNA pieces when a batch of one type of letter (for instance T) is introduced, that letter was incorporated into the growing DNA! If a lot of current is detected when that batch is introduced, a lot of letters were incorporated. Still other techniques use current generation but in a different way. Individual pieces of DNA are passed through tiny pores in a thin membrane. As each letter of the DNA moves through the pore, the passage of electrolytes through the pore leads to a change in current across the membrane. The end result is a current tracing that corresponds to the sequence of letters in that piece of DNA. To learn more about all of the different ways to sequence a genome, check out the following websites: http://www.illumina.com/applications/sequencing/dna_sequencing.ilmnhttp://www.pacificbiosciences.com/products/smrt-technology/http://www.lifetechnologies.com/us/en/home/brands/ion-torrent.htmlhttps://www.nanoporetech.com/news/movies#movie-24-nanopore-dna-sequencingPUTTING IT (i.e. THE SEQUENCE) ALL TOGETHER: Once the individual DNA pieces of a genome have been sequenced, the next step is to reassemble these pieces into the genome that we started from. To do this it is helpful to have an idea of what a typical genome sequence looks like. This typical genome is called a reference genome and it was the major outcome of the Human Genome Project. Each piece of DNA is essentially mapped to this reference genome. Now that we know where in the reference genome each fragment belongs, we are starting to see our own genome emerge. The next step is to figure out where our genome and the reference genome are different. They could be different in several ways. The most common way they differ is that a single letter in our genome at a given position is not the same as the same position in the reference genome. This difference is called a SNP (short for single nucleotide polymorphism, since you asked). They might also differ by having a couple letters missing or otherwise entire chunks of DNA gone or duplicated or have DNA from one section of the genome joined to DNA from a different section of the genome. Each of these differences is called a variant. While not every variant is consequential, the sum of an individual’s variants is largely responsible for the differences between any two different people. Sometimes too, a single letter difference can mean the difference between health and disease- this is usually called a mutation. To learn more about how to assemble the sequence of a genome and what it could mean, check out the following websites: http://www.genome.gov/25019999 and http://www.personalgenomes.org/DEEPER STILL: Several great books have been published that go over this material in greater detail. If interested in biology with an emphasis on molecular genetics, check out Horace Freeland Judson’s The Eighth Day of Creation. If interested in an overview of the technologies, check out Kevin Davies’ The $1,000 Genome. If interested in the Human Genome Project and personalized medicine and the ramifications for medicine and society, check out Francis Collins’ The Language of Life, Matt Ridley’s GENOME or Misha Agrist’s Here is a Human Being.
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TED-Ed
Lesson Creator
New York, NY
12/09/2013 • 
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