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I am doing a project on DNA sequence and on how changes in the sequence cause disorders. For example, cystic fibrosis is caused by a recessive allele. When you look at that string of DNA you can see there are three DNA bases missing. Here are my questions I need answered:

1) What kind of technology you would use when looking for the DNA impurities?

2) In the sequences is it easy to point out the mistakes or are they hard to see?

3) Is a specific name for this action or do I just call it DNA sequencing?

4) Is it possible to replace the mistakes with the correct sequence?

--Thank you
Question Date: 2010-10-13
Answer 1:

We can't use microscopes to see when there's a problem with the DNA unless it's something like having the wrong number of chromosomes or missing a big piece of one. In order to detect a mutation like the one that causes cystic fibrosis, we have to use an indirect method. First, we need to use specific enzymes to cut up the DNA. Enzymes do lots of things, but the ones used here act like "smart scissors." They only cut the DNA in very specific places. DNA is made of a series of units we call bases. We name these bases A, T, G, and C. Let's say we have an enzyme that only makes a cut after it sees a series like CCCCCTTGGGGGAA. It will then cut that strand of DNA into 2 pieces that will be the same size every time. So let's say that that particular sequence is part of the normal gene. If we have 2 pieces of the expected size, we can be almost sure that the gene is normal. Let's say that there's mutation that turns that sequence into CCCCCGGGGGAA. Now the enzyme won't cut the DNA, so we get the whole chromosome instead of 2 pieces. Here's the tricky part, we can't just tell the size of pieces by looking. Instead, we take a sample that has a lot of DNA (that was either cut by the enzyme or not), then put the DNA on one end of a sort of electrified block of gelatin for a particular amount of time. Smaller pieces will travel faster, so we will see blobs of DNA at different locations and tell what size they are. If our DNA was cut, we will see 2 blobs that have moved pretty far across the gel. If our DNA wasn't cut, we'll get one blob and it will be pretty close to the beginning. This process is called gel electrophoresis.

So looking at the gel, or a picture of it, we can tell whether there's a mutation. You don't have to sequence the entire set of DNA to do this, you can just test using the specific enzyme that should make a cut somewhere in the specific gene you're interested in.

It would be great if we could insert the proper sequence of bases so that people could be cured of genetic diseases, but that is science fiction. Maybe we will be able to figure it out in your lifetime, though. Maybe you will even be part of that breakthrough.

Thanks for Asking

Answer 2:

Those are outstanding questions.

You are correct, when a genetic disorder occurs, 'mutations' or 'deletions' in the sequence of nucleic acid bases are found. A mutation is when a base is replaced with another, and a deletion is when one is absent. You've just described a deletion for cystic fibrosis.

To specifically address you questions:

1. What kind of technology?

There are many kinds of technology that are currently used to sequence DNA. Many of these technologies rely on a parent technology called "polymerase chain reaction", or PCR as it is commonly referred to. What that technology does is produce millions of exact copies of the DNA so that sequencing is even possible.

Many of the technologies that are used for sequencing rely on slight differences in chemistry of the 4 bases in DNA. The list of technology is rather expansive, so please ask again if you would like more specifics.

2. Is it easy to point out mistakes in the sequence?

Sometimes yes, sometimes no. If you know what the sequence is supposed to look like, then it can be easy to spot the errors. However, determining what the sequence is supposed to be, and what certain mutations or bases do is non-trivial. Unfortunately, there is no clear answer. My safe answer is, "it depends".

Your question is also philosophical. How do you know that a mutation or a deletion in the genetic sequence is a mistake? If animals are constantly evolving, that means that mutations and deletions are happening. Sometimes such changes are beneficial, sometimes they are harmful. If we narrow the discussion to genetic diseases and disorders, we can just refer to changes in the genetic sequence as mistakes.

3. Can you call the action DNA sequencing?

Yes. You can also call it genetic sequencing.

4. Is it possible to correct the mistakes?

In theory, yes. In practice, maybe. This is a current and exciting area of research. It is often referred to as gene therapy. There are many issues with this concept. Some technical, some scientific, and some ethical.

Technical and scientific issues: The cell and the body are exquisitely complex. Perturbing one portion of the genetic sequence may affect another. It becomes very difficult to specifically target certain areas of the sequence. It is also extremely non-trivial to access the genes in all cells of the body, change their genetic code, and allow them to proceed as normal.

Ethical: One particular way of doing 'gene therapy', although you might not think of it as such, is when one becomes infected with certain types of viruses. Some of these viruses actually alter the genetic sequence. Some biologists and chemists are trying to specifically engineer these types of viruses to cure diseases rather than cause them. Also, broadly and simply speaking, our genes define us as who we are. Some argue that changing our genes can change who we are, although I caution you that this is a highly debatable argument, both on scientific and ethical grounds.

Please let us know if you have any more questions, or if you would like elaborations of any of these answers.

Best of luck with your project.

Answer 3:

1) What kind of technology you would use when looking for the DNA impurities?

It's called DNA sequencing, a rather complex technology where you get as a result, a sequence of letters (eg ...GATTACA...) where each letter stands for one of the four DNA nucleotides, also called bases, in the order they appear in the DNA sample. Rather than being impurities, there will always be differences (called mutations) in the DNA of different organisms (except for identical twins or in cloned organisms).

2) In the sequences is it easy to point out the mistakes or are they hard to see?

Once you know the region within the sequence where you are interested in finding mutations, all you have to do is compare that region in the sequence to the same region of a regular or reference sequence (one without that particular mutation). An example could look like:

...GATTATA... (part of the sample sequence)
...GATTACA... (the reference sequence)

In this case, you can easily spot a mutation from C to T in the sample sequence.

3) Is a specific name for this action or do I just call it DNA sequencing?

Most of the time, the term "DNA sequencing" also implies a comparison to a reference sequence (whenever one is available) so yes, you can call it that.

4) Is it possible to replace the mistakes with the correct sequence?

This is the goal of Gene Therapy, a science still in its infancy but with great promise for the future.

Answer 4:

When a DNA sequence changes it is called a mutation. Mutations can be caused by errors in meiosis or DNA replication, which can be passed on from parent to child, or by environmental factors like radiation and chemical exposure. Some mutations, not all, can result in disease. To find out if there is a mutation in a persons gene that is possibly causing disease, scientists use DNA sequencing technology. There are several different methods, the most common for diagnostics being dye-terminator sequencing. The basic idea is that each DNA base (A, T, C and G) is labeled with a different color dye, so that you can tell the sequence based on the order of light color. There are automated DNA-sequencing machines out there, so all doctors have to do is put in the patients sample and out pops the DNA sequence for the gene they are interested in.

Some diseases are normally caused by the same DNA mutation, like cystic fibrosis. If the gene associated with the disease is known, then it is easy to find a mutation through DNA sequencing by comparing it to a normal sequence. Other diseases, like breast cancer, may be linked to several different mutations and therefore much harder to identify.

Gene therapy is where genes are inserted into a persons cells to replace the genes that carry mutations. This is a very new and exciting field of science but still has a lot of problems that need to be worked out. Scientifically, there can be an immune response to the foreign DNA and if the DNA inserts into the wrong place it can cause a tumor to grow. Ethically, it has not been shown whether or not DNA inserted into peoples cells can be passed on to their children. If it can, then we could basically be genetically engineering human beings to have whatever genes we wanted. So to answer your question, it is possible to replace the mistakes but at what cost?

Answer 5:

Finding changes in the genetic code is a multi-step process. Initially, you need to sequence part of the gene, and I know it's expensive. The next step is to make a primer sequence copy of the gene, and then link it up to the gene in question so that polymerase chain reaction procedures can get you the rest of the gene quickly. Then you can sequence the genes of multiple individuals, or a much longer sequence, much more quickly.

You can't effectively change the genes of a living person, because you would have to change the DNA of every cell in the person's body, and there are about a hundred trillion cells in the human body.

Answer 6:

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