Genes are often called the “blueprint” of the human body. In reality, they are constraints on an environmental process. Imagine you have been given three crayons to colour in a sheet of paper: red, green and blue. You can colour the page in any way you want at the time (that’s the environmental part) but you can only use red, green or blue (the genetic part). In the same way, someone may have the gene for being tall, but if they don’t get enough food, they won’t grow as well.
Genes are small sequences of chemicals linked together in a thread. When you join genes together in a long chain, it’s called DNA. DNA is wrapped around itself, curled up and squished together to form a chromosome.
The picture to the left shows the how the DNA double helix (bottom) twists up to form a chromosome (top). We don’t really need to know about DNA in regards to Tourette’s, so all you have to know is that a small part of a chromosome is a gene.
Chromosomes are the X shaped creatures that are so recognizable in Genetics. Most of the time, chromosomes don’t look like an X. They only have this shape just before they divide (this is the only time we can see them). They look like this because the left half of the chromosome goes one way, and the right half goes the other. The two halves of a chromosome are exactly the same as each other, they are copies.
Humans have 46 chromosomes: 44 autosomes and 2 sex chromosomes.
The sex chromosomes determine whether you are male or female; males have one X
chromosome and one Y chromosome, females have two X chromosomes (notice the
picture on the right of the screen is from a male).
The autosomes are, basically, all the other ones.
The autosomes are the ones we’re interested in.
The 44 autosomes are grouped into pairs of the same size and function – so 22 pairs. The chromosomes in a pair have the same genes, but different
genotypes. What I mean is, if the instructions for eye colour were halfway down chromosome 3 (I’m sure it isn’t…it’s just a
hypothetical) both chromosomes in pair 3 will have the eye colour instructions half way down. But one
of the pair may be for blue eyes, while the other one is for brown. Every person (excluding genetic abnormalities) has two sets of instructions for each trait.
The human body can’t have both blue and brown eyes though. It needs to know which to use. So it picks the dominant one, and ignores the other. In this example, brown is dominant over blue, so a person with both a blue gene and a brown gene would have brown eyes. The only way they would have blue eyes is if they had two blue genes. Then, because they are both recessive (not dominant) blue would be shown. If a person has two dominants (brown) then they will have brown eyes.
Scientists use special notation for genes. Simply, a gene (let’s stick with eye colour) is given a letter, we’ll use “b”. The dominant gene is given a capital letter (i.e. B = brown) and the recessive gene is given a small letter (i.e. b = blue). A person’s genotype (what genes he has) can then be written as BB, Bb, or bb. BB is two brown genes, Bb is a brown and a blue, and bb is two blue genes.
Confusingly (at least to me) scientists also use capital letters to denote the presence of a particular genotype.
I will be using the example “GTS” to represent the main Tourette syndrome/combined tic trait gene. So GTS means a person
has a Tourette gene, and gts means they don’t have a Tourette gene. Once again a person can be
GTSGTS, GTSgts, or gtsgts.
When someone has two of the same gene (e.g. GTSGTS or aa) they are said to be homozygous. When someone has two different ones (e.g. GTSgts or Aa) they are heterozygous.
Tourette Syndrome is not as simple as eye colour though. It is not caused by one gene, but by many. Some of these genes are dominant, some are recessive, some are equal in value to another one, so they combine to form a different phenotype (appearance). An example of genes that combine is the snapdragon. If you cross a pink snapdragon R1R1 with a white one R2R2 you will get R1R2 snapdragons, which are a purple colour. That is, one white gene and one pink gene combine to make one purple flower.
Tourette syndrome is said to be autosomal semi dominant. That means it is not located on sex chromosomes, and if you have the main gene you are likely, but not certain, to have Tourette syndrome.
GTS is the main gene for Tourette Syndrome, but it also codes for Obsessive Compulsive Disorder and Chronic Tic Disorder. This means if you have the GTS gene, you can be affected by TS, OCD or CTD. It also means a parent with OCD can give birth to a Tourette child, or, a Tourette parent can give birth to a Chronic tic child, etc.
Tourette's, however, is related to sex in some way. It has been found that testosterone and other androgens (male sex hormones) exacerbate Tourette Syndrome. This probably explains why Tourette’s is 3-4 times more likely in males. It is likely that females with severe cases of Tourette’s either inherited the gene from both parents (rare) or have unusually high androgen levels.
The GTS gene appears to be at 11q23. That is, on gene 11 at position 23. That doesn’t really mean a huge amount until we can find out
exactly which specific gene in 11q23 is the trigger for
Tourette's. However, it is important to realise which area we are looking
at, as I will explain in the section Dr Comings and me.
If I have a GTS gene, what is the chance I’ll show Tourette syndrome?
Well, if you are a male and have gotten two GTS genes (one from each parent) it is a statistical certainty you will have a GTS phenotype (i.e. you will have TS, OCD, CTS or one of the other related conditions). The penetrance is 1. (In probability, 1 is a certainty - yes, 0 is a certainty - no, and the numbers in between are a grading between those two points.)
If you are a female and have two GTS genes (one from each parent) you have a penetrance of 0.709, or 70.9%
chance of displaying the phenotype.
If you are male and have only one GTS gene (genotype GTSgts) you still have a penetrance of 1. That is, 100% of you will show the TIC phenotype. If you are female and have genotype GTSgts, you will also have the same penetrance as a GTSGTS female. That is, 0.709 or 70.9%.
If neither of your parents passes on a GTS gene and there are no random mutations, your genotype is gtsgts. For females, this translates into 0 penetrance, statistically impossible for you to have the GTS phenotype. For males, you’re not completely safe; penetrance is at 0.002 or 2 in 1,000. (Note I say
"statistically impossible"; there are exceptions to every rule.)
All this penetrance stuff is nice, but what does it mean in the actual population?
To work out what this means in the real world we have to know how common the gene GTS is in the total population. I’ll take Walkup, LaBuda, Singer, Brown, Riddle and Hurko (1996) at their word and say that the frequency of the GTS gene is 0.01, or 1 in every 100 genes is GTS and 99 in every 100 is tic. So we put that figure into a Punnett square.
In a Punnett square one side is used to represent the possible genes from the mother, the other side the genes from the father. Then to get the probability of a child having a particular gene, you multiply the figures at the top of the page with those at the side.
Badly explained wasn’t it! I’ll walk you through an example.
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Therefore: 199/10,000 have the GTS gene. Penetrance is approximately = 1 Therefore approx. 2 in 100 have GTS spectrum phenotype, For females: 199/10,000 x 0.709 = 0.0141091=1.41 in 100 For males: 199/10,000 x 1 = 1.99 in 100 |
Let’s try and work out the probability of a random person having the genotype GTSGTS. For this to happen the child needs to get the GTS gene from both parents. The left hand column of the top line of the square in picture to the left says the probability of getting the GTS gene from that parent is 0.01 (we got that figure from Walkup et al. remember?) The top row in
the left of the square in the same picture shows that the probability of getting the GTS gene from that parent is also 0.01. So to get the probability that a child will get GTS from both parents, you multiply the probabilities together. 0.01x0.01 = 0.0001 or one in 10,000.
If you do that with all the other gene combinations you get 1 in 10,000 with genotype GTSGTS, 198 (99+99) in 10,000 with genotype GTSgts, and 9801 in 10,000 with genotype gtsgts. This means 199/10,000 have at least one GTS gene. Which is roughly equal to 2/100. If we then take the average penetrance for the TIC gene, which is 1, we see that approximately 2 out of every hundred people have Tourette syndrome
or a related condition.
You’ve probably seen people say Tourette’s affects 2/100 people. (Even I’ve said that so far.) But from these figures it’s not strictly true, 2/100 people have the phenotype of the GTS gene, that is Tourette’s or Chronic Tic or Obsessive Compulsive disorder or male type II alcoholism or…and so on. This takes Tourette’s out of the reasonably common category it’s currently in and gives it the rare status it enjoyed years ago.
So when you see a modern website saying Tourette’s affects 1/50, and then an old one where it says 1 in 200 or so, the older one is probably right. Makes you feel special doesn’t it.
In that example, you can also see where I’ve worked out the “exact” population saturation of the GTS gene using Pauls and Leckman’s figures. They come out at 1.99 in every 100 males have GTS phenotype and 1.41 in every 100 females has GTS phenotype. But if you remember, a few paragraphs ago I said that males were 3-4 times more likely to have Tourette’s than females. Obviously, although showing the signs of the GTS gene are almost the same for both sexes, the expression of Tourette’s itself is highly sex weighted.
Turning back to Walkup et al (1996) we are told that the penetrance of Tourette syndrome is 2.2 for males and 0.3 for females. So, if you can follow what I’ve done on the right;
| Reference: Walkup et al. Penetrance of Tourette
syndrome is: from above equations -> 0.198 are heterozygous 2.2/100 x 0.198 = 0.004356 for males from above equations -> 0.0001 are homozygous 0.004356 + 0.0001 = 0.004456 or 4.4/1,000 males have TS Average of two results = 5/2,000 |
So feel proud, we've proved something new today!☻
