An introduction to genetic mutations

0:01Voiceover: Today I'm going to give you a quick introduction into genetic mutations. But first, let's go over the central dogma of molecular biology, which is just the idea that genetic information in a cell is formed in the form of DNA. This DNA is used to generate complimentary RNA through a process called transcription.

0:20That RNA is then used to synthesize a corresponding protein through the process of translation. Looking at a quick example, our short DNA strand here will be used to generate an RNA stand. Remember that A pairs with U or T and C pairs with G. Next, our RNA will be used to generate protein through translation.

0:39Remember that during this process, RNA nucleotides are read in groups of three, called codons, in order to generate corresponding amino acids. Just very generally, we say that mutations >>have the affect of making this synthesized protein not turn out quite right.

0:57I'm going to give a quick shout-out to sickle-cell disease, which is an example of a disease that's caused by a genetic mutation. You may remember that there is a protein in red blood cells called hemoglobin, which we can also call Hb. Hemoglobin in a protein that coordinates to iron ions in order to hold onto oxygen molecules and transport them throughout the body.

1:17The mutation that causes sickle-cell disease results in a mutated form of hemoglobin called HbS being formed, where the S is for the word sickle. The difference between normal hemoglobin and HbS is that one glutamate amino acid residue is being replaced with a valine amino acid residue.

1:34This small change results in all of these mutated HbS proteins aggregating together in a red blood cell, which makes it very difficult for that red blood cell to transport oxygen effectively. Just a side point, remember that red blood cells are initially generated from hematopoietic stem cells through a process called hematopoiesis.

1:55Where are mutations found, and how do they come up in the first place? Let's look at a couple of different possible mistakes that could lead to an incorrectly produced protein. First, we'll see what happens if a cell makes a mistake during translation. We'll stick with our example of sickle-cell disease from before.

2:11Let's say that we have this sample piece of DNA with three nucleotides from the gene coding for hemoglobin. This DNA is transcribed to form the complimentary RNA sequence GAG. That GAG would normally correspond to a glutamate residue during translation, but a mistake during translation might lead to a valine residue being translated instead to produce the mutated hemoglobin associated with sickle-cell disease.

2:34But notice that if a mutation happens during translation, the cell will only produce one mutated hemoglobin, or HbS, for each overall mistake. Since cells are making tons and tons of hemoglobin, just one mutated protein might not have that big of an effect on the cell.

2:50So we can say that mistakes during translation probably don't cause mutations like the one associated with sickle-cell disease. Next, we'll look at mistakes during transcription. Again, we have our CTC piece of DNA, which would normally make GAG on RNA, but maybe a mistake occurs which leads to the transcription to a GUG instead, which would then code for the valine associated with mutated hemoglobin.

3:13If this mistake occurred, the cell would only make a few mutated hemoglobins for each mistake since an individual strand of messenger RNA will only be translated a couple of times before being degraded. >>So we can say that mistakes during transcription probably don't cause mutations like the one associated with sickle-cell disease.

3:31Finally, we'll look at mistakes in the DNA strand. If our CTC in DNA is mistakenly turned into a CAC, then our corresponding RNA from transcription will be changed and ultimately a valine would be produced instead of a glutamic acid. Now, since a cell's DNA stores all of its genetic information, that mistake would lead to all future hemoglobins produced from that gene being mutated.

3:55So overall, we can say that mutations will usually result from mistakes in a cell's DNA and not from the RNA or the protein. So where do these types of mutations come from? There are two ways a person can get a genetic mutation. The first is that they inherit it from their parents.

4:12Remember that DNA is passed down from parents to offspring, so if we have a mutated father here, then there's a good chance that at least one of his kids will inherit that mutated gene the same way that the child might inherit any amount of that parent's DNA. The other possibility is that the mutation will come on spontaneously, which is where a person suddenly gets a mutation in their DNA without their parents having had the same mutation.

4:35Spontaneous mutations can come from many different sources, with just a few examples being from DNA replication errors, environmental factors like certain poisons. It's also possible that genetic mutations can come on entirely randomly. What did we learn? First we learned that mutations originate at the DNA level, and not the RNA or protein level.

4:57The effects of the mutation, like the example we gave of sickle-cell disease, are found with problems with the proteins that are ultimately expressed by the mutated DNA. Now, like every rule, there are a couple of exceptions to this one, but we can say that the effects of a mutation are usually found at the protein level.

5:16Finally, we learned that mutations are either inherited from a parent, or come on entirely spontaneously.