THE CHROMOSOMES/GENES INVOLVED

Hi guys, do you still remember me? We talked about the Huntington's disease right previously?

Don't you ever forget that because we might not know that some of you are actually inherited this disease in your body. The previous post might help you to identify if you are having this inherited disease or not. 

So, we already know what it is actually about, it's prevalence and characteristics, symptoms, their unique features as well as how this disease inherited and developed.

Can you all guess what i'm going to share this time?

Noooo, it's still not finish yet. There's few things that we haven't talked about yet😄

Ahaaaaaaaaa!!! Correct!

I'm going to tell you what is the genes or chromosomes involved in this Huntington's disease.

Have you guys  ever wonder what happens to the genes in our body that lead to this disease? What did our genes do wrong in the body which affected our entire life? 😱

Hmm before I start, do you guys know what is the genes? And what is the difference between genes and chromosomes?

Okay, enough with all the questions, I know I ask too many questions right hahaha😂 So now, let me clarify all these things to you.

A gene is a piece of biological information you inherit from your parents. It is present in every cell of the body and tells cells what to do. Genes control cells by producing proteins, each gene is really a kind of recipe for making a certain protein. Genes are usually attached to a chromosome. Chromosome is a strand of DNA containing many different genes. Each human cell contains around 25,000 genes and most have 23 pairs of chromosomes. 

The Huntington's gene, the gene that determines whether you will develop Huntington's disease is attached to chromosome pair number 4. 

Previously, I had mention that this disease developed due to the mutation, isn't it?

Yes, it is due to a mutation in the HTT gene which cause the Huntington's disease. The HTT gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it appears to play an important role in nerve cells which is neurons in our brain. 

The HTT mutation that causes the Huntington's disease involves a DNA segment know as CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks which is cytosine, guanine and adenine that appears multiple times in a row. Normally, the CAG segments is repeated 10 to 35 times within the genes. In people with Huntington's disease, the CAG segment is repeated 36 to more than 1200 times. People with 36 to 39 times CAG repeats may or may not develop the signs and symptoms of Huntington's disease whereas people with 40 or more repeats almost always develop this disorder. 

Scary right?

But, what makes more scarier is when there is an increase in the size of the CAG segment. This will leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal function of these cells. The dysfunction and eventually death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington's disease. 

I know you kinda feel anxious and frightened now, but just bear with me a little bit. I want to add some more. 

For you guys information, as the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington's disease typically have 40 to 50 CAG repeats in the HTT gene, while people with the juvenile form of the disorder tend to have more than 60 CAG repeats. 

Oh wait, what is the juvenile Huntington's?

Juvenile Huntington's is when the genes produces an even larger number of CAG repeats that with adult Huntington's, with the result that symptoms start to appear earlier which is before age of 21. Juvenile Huntington's is quite rare actually, less than 10% of people with the disease will have Juvenile-onset. People with Juvenile Huntington's often experience some symptoms that are quite different from adult Huntington's. If you have it, you are less likely to have the involuntary movements known as chorea. But, you are more likely to experience muscle contractions and stiffness, making the movements more slower and difficult. You may also develop epilepsy or seizures. 

Individuals who have 27 to 35 repeats in the HTT gene do not develop Huntington's disease, but they are at risk of having children who will develop this disorder. As the gene is passed from parent to child, the size of CAG trinucleotide repeat may lengthen into the range associated with Huntington's disease which is 36 repeats or more.  

You can refer to this graph below to help you gain more understanding on how the CAG repeats affect the generation. 

Hold on, we are almost close to the end!

Before I close this chapter for today since I'm already sleepy😴, I leave you with an image. I want you to digest this image clearly until you dream about it okay😉

The image below gives you an idea on how the genes altered which lead to Huntington's disease.

Finally, I'm done! Thank you for bear with me and you can always ask me if you have any curiosity regarding this topic. So,we talk again next time, okay? Have a nice day! 

Bye and assalamualaikum😊