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"Confetti Skin, Beauty Within" is our blog about ichthyosis and its effect on our lives. Rachel and our three boys are affected with the form of ichthyosis called "icthyosis en confetti, type 2".

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Here's our summary of our best and most important posts of 2012.

Genetics Part 1 – What’s a Gene, Anyway?

One of the most common questions that I see about ichthyosis is, “If I have another child, will he or she be affected, too?” The other winner in the common question derby is, “What kind of ichthyosis do I have?” Both questions ultimately come down to genetics.

So…what’s a gene?

A gene is a short strand of DNA that codes for a protein that does something, or a lot of somethings, somewhere in your body. For the most part, proteins are things like enzymes, receptors, hormones and gates.

Enzyme – a chemical that makes a molecule in your body change into a different molecule. You know those little tourist penny-squishing machines at carnivals and museums and highway rest stops? You put the penny in, turn the crank, and out comes an oval penny with Mickey Mouse embossed on it. The penny is the molecule, and the machine with the crank is the enzyme.

Gate – lets stuff in or out of cell. But like the bouncer in front of the bar, it only lets in certain qualified individuals. Most cells have hundreds of gates to let in hundreds of different molecules.

Receptor – a protein on the outside of the cell that catches hormones and tells the inside of the cell to do things, but only when the hormone is attached. It’s like a lock on the front door. For example, an insulin receptor tells the sugar gate to open and to suck in all the excess sugar in the blood. The end result is lower blood sugar. But you wouldn’t want that gate working all the time because sugar would get too low and you’d pass out. So it only works when there’s insulin around.

Hormone – this is the key that goes in the lock. It tells the cells to grow or open gates or do all sorts of other things. One part of your body makes the hormone and it gets used all over the body.

DNA is made of 4 chemicals called nucleic acids. There are 4 nucleic acids, A, T, G, and C. They get copied into RNA and made into proteins or copied identically so that when the cell splits into 2 each new cell has its own copy. Just as knowing your alphabet does not mean that you can read words, sentences or novels, DNA is not the end of the line when it comes to protein making. ATCG are used to make 3 letter “words”, called amino acids. There are 64 possible “words.” The DNA is in a certain order, and therefore, the 3 letter words are in the same order. A string of amino acid “words” make “sentences,” or proteins, and finally the cell folds up the protein into a specific shape and sends it off to get used as a gate or receptor or hormone or enzyme.

Think about it like this:

ABCDEFG (26) –> AND, THE, FOR, WHY, HOW (1000s)–> ONE DAY, THE CAT ATE THE DOG. (millions)

ATCG (4)–> AAA, ATC, CAC, TAG (64) –> Proline, leucine, alanine, tyrosine (23 acids and a stop sign)

Most of the time, when cells divide, they make perfect copies. Sometimes, though, as the DNA is getting replicated, a mistake is make. This page says that 120 mutations happen out of 6 billion nucleic acids. Many mistakes make no difference. There are 64 “words” but only 24 amino acids. Many times, the mistake results in the same amino acid. CCC makes proline, but so does CCG and CCA.

Then we have the real mutations. These happen in 3 general ways:

Substitutions – a single mistake that results in a different amino acid. When the protein folds up, the mistake means that the protein folds backwards or twists sideways. The gate is broken. The lock no longer takes the key.

Imagine that you had a sentence: “Bring the baby over there.”

Now, as we see so often, someone accidentally types out “Bring the baby over their.” The sentence still makes sense, even though it is misspelled. The meaning is not changed, as anyone reading it still knows what was intended. CCC got changed to CCA.

Now, imagine that our typist forgot the T. “Bring the baby over here.” The meaning is completely changed. Proline became alanine. Now the protein doesn’t work.

Missense. Sometimes, a whole chunk of DNA gets inverted, stuck in the middle of a different gene, or other errors. Imagine that someone meant to type “Once upon a time,” but their fingers shifted on the keyboard. The end result reads “Pmvr i[pm s yo,r.” Say what? Your protein making machinery can’t understand it any better than your eyes can, and so you end up with no functioning protein.

Deletions (or Frame-shift mutations). In a deletion, a single nucleic acid (or sometimes a large chunk) don’t make it into protein form. A string of, say, AATCGATTA might become AACGATTA. When made into a protein, the intended breakdown is AAT, CGA, and TTA. But with the deletion, you get completely different words, AAC, GAT, and TA?. The protein might end up with a stop sign in the middle, or with the wrong words. When it comes time to fold the protein into a usable shape, it is too short or bends the wrong way. If proteins were words, it would look like this:
Intended: “To be, or not to be, that is the question.”
Mutation: “To bo rn ott ob et, hati, st heq uestion.”

Similarly, you can have an Insertion, in which case the result is “To bbe ,o rno tt ob, etha ti st heq uestion.”

Nonsense. In this case, the deletion causes the protein to stop. It is like a period in the middle of a sentence. In the cell, the result is no functioning protein at all.
Intended: “I ate ice cream and cake.
Mutation: “I ate.”

Where the mutation happens makes a difference, too. Proteins fold up into particular shapes, so if the mutation happens at a vital location that determines whether the protein is made correctly or not, then that region is called a “hot spot.” Think about it like this: you have a trash bag and it gets a hole. If the hole is near the top where you tie it, no big deal. But if that hole is in the bottom of the bag and slime is oozing out, then you find a big mess when you carry off the bag. That’s a much bigger problem!

This is a series of posts on genetics. More information is available in the following links:
Genetics 1: What’s a Gene?  <–You Are Here
Genetics 2: Recessive Inheritance
Genetics 3: X-Linked Inheritance (X-linked Ichthyosis)
Genetics 4: X-Linked Inheritance (CHILD Syndrome)
Genetics 5: Dominant Inheritance
Genetics 6: Mosaicism
Genetics 7: Video explanation of how mutations work
Genetics 8: Why we don’t do automatic prenatal screening for ichthyosis

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